Star Update Podcast - Cardiology News Summaries

View Details

Pulmonary Vein Isolation vs Sham Intervention in Symptomatic Atrial Fibrillation: The SHAM-PVI Randomized Clinical Trial

JAMA 2024 Sep 2:e2417921. doi: 10.1001/jama.2024.17921

Abstract

Importance: There are concerns that pulmonary vein isolation for atrial fibrillation may have a profound placebo effect, but no double-blind randomized clinical trials have been conducted.

Objective: To determine whether pulmonary vein isolation is more effective than a sham procedure for improving outcomes in atrial fibrillation.

Design, setting, and participants:Double-blind randomized clinical trial conducted at 2 tertiary centers in the UK between January 2020 and March 2024 among patients with symptomaticparoxysmal or persistent atrial fibrillation. Major exclusion criteria included long-standing persistent atrial fibrillation, prior left atrium ablation, otherarrhythmias requiring ablative therapy, a left atrium of 5.5 cm or larger, and ejection fraction of less than 35%.

Intervention: Participants were randomly assigned to receive pulmonary vein isolation with cryoablation (n = 64) or a sham procedure with phrenic nerve pacing (n = 62).

Main outcomes and measures: The primary end point was atrial fibrillation burden at 6 months, excluding a3-month blanking period. Secondary outcomes included quality-of-life measures, time to events, and safety. Atrial fibrillation burden was measured by an implantable loop recorder.

Results: A total of 126 participants were randomized (mean age, 66.8 years; 89 men [70.63%]; 20.63% with paroxysmal atrial fibrillation). The absolute mean atrial fibrillation burden change from baseline to 6 monthswas 60.31% in the ablation group and 35.0% in the sham group (geometric mean difference, 0.25; 95% CI, 0.15-0.42; P < .001). The estimated difference in theoverall Atrial Fibrillation Effect on Quality of Life score at 6 months, favoring catheter ablation, was 18.39 points (95% CI, 11.48-25.30 points). The Short Form 36general health score also improved substantially more with ablation, with an estimated difference of 9.27 points at 6 months (95% CI, 3.78-14.76 points).

Conclusions and relevance: Pulmonary vein isolation resulted in a statistically significant and clinically important decrease in atrial fibrillation burden at 6 months, with substantial improvements in symptoms and quality of life, compared with a sham procedure.

Disclaimer:

Lupin makes no representation or warranty of any kind, expressed or implied, regarding the accuracy, adequacy, validity, reliability, availability, or completeness of anyscientific information shared by the HCP on the STAR UPDATE podcast. You should not allow the contents of this to substitute for your own medical judgment, which you should exercise in evaluating the information on thiswebsite.

View Details

2024 European Society of Cardiology Guidelines for Management of Elevated BP and Hypertension: Key Points

European Heart Journal, ehae178, https://doi.org/10.1093/eurheartj/ehae178

The key points to remember from the 2024European Society of Cardiology (ESC) guidelines for the management of elevated blood pressure (BP) and hypertension are:

· The most important point is that the targetsystolic BP (SBP) for adults receiving BP medications should be 120-129 mm Hg. One can “opt-out” of this goal for patients who cannot tolerate that level ofBP, patients who have orthostatic symptoms, patients who are over 85 years old or have frailty, or patients with limited life expectancy. For those patients, the goal is as low a pressure toward that goal as can be achieved.

· Blood Pressure is defined as having a continued risk rooted in time of exposure to higher Blood Pressure. For this reason, hypertension is defined as an systolic BP (SBP) >140 mm Hg or diastolic BP (DBP) >90 mm Hg, but a new category of “elevated BP” has been introduced that is an office systolic BP of 120-139 mm Hg or diastolic BP 70-89 mm Hg. This guideline recognizes that risk increases across this scale, rather than starts at a certain level that is defined as “hypertension.” This category of “elevated BP” reminds us of the term “prehypertension” used in JNC-7 (Seventh Report ofthe Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure).

· The guideline focuses on true risk reductionrelated to fatal and nonfatal cardiovascular outcomes. The longstanding tendency of using the surrogate marker of Blood Pressure alone does not supporta Class I indication in this guideline, except for lifestyle and low-risk nondrug interventions.

· Out-of-office BP is recommended for diagnosticpurposes as it can detect white-coat and masked hypertension. Office measurements can be used when out-of-office readings are not obtainable.

· Lifestyle interventions are recommended for 3months. If not fully successful, then drug therapy should be started.

· In pregnant women without contraindications andin consultation with an obstetrician, low- to moderate-intensity exercise can reduce the risk of gestational hypertension and pre-eclampsia and should beconsidered.

· A risk-based approach to hypertension treatmentis recommended, noting that those with diabetes, kidney disease, cardiovascular disease, target organ damage, and diabetes of familial hypercholesterolemia areat increased risk for cardiovascular disease. More time and resources should be devoted to patients at higher overall risk from elevated BP.

· Screening for secondary hypertension is recommended for adults diagnosed with hypertension before the age of 40 years, except for obese young adults for whom screening for sleep apnea should be a first step.

· Self-measurement of BP is recognized to improvepatient empowerment and adherence to treatment.

· It is recognized that the major weakness ofclinical hypertension guidelines is poor implementation. The document includes sections on how to overcome barriers to implementation.

· In patients with atrial fibrillation, manual BPsshould be used, as most automated devices have not been validated for BP measurement in patients with atrial fibrillation.

· The guidelines include sex and gender throughoutthe document. It defines sex as a biological condition of being male or female from conception, based on genes. Gender is a sociocultural dimension of being aman or a woman in a society based on gender roles and norms.

Disclaimer:

View Details

Transcatheter Valve Repair in Heart Failure with Moderate to Severe Mitral Regurgitation

DOI: 10.1056/NEJMoa2314328

Background

Whether transcatheter mitral-valve repairimproves outcomes in patients with heart failure and functional mitral regurgitation is uncertain.

Methods

We conducted a randomized, controlled trialinvolving patients with heart failure and moderate to severe functional mitral regurgitation from 30 sites in nine countries. The patients were assigned in a1:1 ratio to either transcatheter mitral-valve repair and guideline-recommended medical therapy (device group) or medical therapy alone (control group). Thethree primary end points were the rate of the composite of first or recurrent hospitalization for heart failure or cardiovascular death during 24 months; therate of first or recurrent hospitalization for heart failure during 24 months; and the change from baseline to 12 months in the score on the Kansas CityCardiomyopathy Questionnaire–Overall Summary (KCCQ-OS; scores range from 0 to 100, with higher scores indicating better health status).

Results

A total of 505 patients underwent randomization: 250 were assigned to the device group and 255 to the control group. At 24 months, the rate of first or recurrent hospitalization for heart failure or cardiovascular death was 37.0 events per 100 patient-years in the device group and 58.9 events per 100 patient-years in the control group (rate ratio, 0.64; 95% confidence interval [CI], 0.48 to 0.85; P=0.002). The rate of first or recurrent hospitalization for heart failure was 26.9 events per 100 patient-years in the device group and 46.6 events per 100 patient-years in the control group (rate ratio, 0.59; 95% CI, 0.42to 0.82; P=0.002). The KCCQ-OS score increased by a mean (±SD) of 21.6±26.9 points in the device group and 8.0±24.5 points in the control group (mean difference, 10.9 points; 95% CI, 6.8 to 15.0; P<0.001). Device-specific safety events occurred in 4 patients (1.6%).

Conclusions

Among patients with heart failure with moderate to severe functional mitral regurgitation who received medical therapy, the addition of transcatheter mitral-valve repair led to a lower rate of first or recurrent hospitalization for heart failure or cardiovascular deathand a lower rate of first or recurrent hospitalization for heart failure at 24 months and better health status at 12 months than medical therapy alone.

Disclaimer:

View Details

2024 European Society of Cardiology Guidelines for Management of Chronic Coronary Syndromes: Key Points

European Heart Journal, ehae177, https://doi.org/10.1093/eurheartj/ehae177

The key points to remember from the 2024European Society of Cardiology (ESC) guidelines for the management of chronic coronary syndromes (CCS) are:

· The term chronic coronary syndromes describesthe clinical presentations of coronary artery disease (CAD) during stable periods, particularly those preceding or following an acute coronary syndrome (ACS). Of note, symptoms of myocardial ischemia due to obstructiveatherosclerotic CAD overlap with those of coronary microvascular disease or vasospasm. Characterization of endotypes is important to guide appropriate medical therapy for angina with nonobstructive coronary arteries(ANOCA)/ischemia with nonobstructive coronary arteries (INOCA) patients.

· Managing individuals with suspected CCS involvesfour steps:

The first step is a general clinical evaluation that focuses on assessing symptoms and signs of chroniccoronary syndromes, differentiating noncardiac causes of chest pain and ruling out acute coronary syndrome. This initial clinical evaluation requires recording a 12-lead resting electrocardiogram, basic blood tests, and inselected individuals, chest X-ray imaging and pulmonary function testing. This evaluation can be done by the general practitioner. The second step is a furthercardiac examination, including echocardiography at rest to rule out left ventricular (LV) dysfunction and valvular heart disease. After that, it is recommended to estimate the clinical likelihood of obstructive CAD to guidedeferral or referral to further noninvasive and invasive testing. The third step involves diagnostictesting to establish the diagnosis of CCS and determine the patient’s risk of future events. The final step includes lifestyle and risk factor modification combined with disease-modifying medications. A combination of antianginal medications is frequently needed, and coronary revascularization is considered if symptoms are refractory to medical treatment or if high-risk CAD is present. If symptoms persist after obstructive CAD is ruled out, coronary microvascular disease and vasospasm should be considered.

· The inclusion of risk factors to classic pretestlikelihood models of obstructive atherosclerotic CAD improves the identification of patients with very low (≤5 %) pretest likelihood of obstructive CAD in whom deferral of diagnostic testing should be considered.

· First-line diagnostic testing of suspected CCSshould be done by noninvasive anatomic or functional imaging. Selection of the initial noninvasive diagnostic test should be based on the pretest likelihoodof obstructive CAD, other patient characteristics that influence the performance of noninvasive tests, and local expertise and availability.

· Coronary computed tomography angiography (CCTA)is preferred to rule out obstructive CAD and detect nonobstructive CAD. Functional imaging is preferred to correlate symptoms to myocardial ischemia, estimate myocardial viability, and guide decisions on coronary revascularization. Positron emission tomography is preferred for absolute myocardial blood flow measurements, but cardiac magnetic resonance perfusion studies may offer an alternative. Selective second-line cardiac imaging with functional testing in patients with abnormal CCTA and CCTA after abnormalfunctional testing may improve patient selection for invasive coronary angiography (ICA).

· Invasive coronary angiography is recommended todiagnose obstructive CAD in individuals with a very high pre- or post-test likelihood of disease, severe symptoms refractory to guideline-directed medical therapy (GDMT), angina at a low level of exercise, and/or high event risk. When ICA is indicated, it is recommended to evaluate the functional severity of ‘intermediate’ stenoses by invasive functional testing (fractional flow reserve, instantaneous wave-free ratioi) before revascularization.

· A single antiplatelet agent, aspirin or clopidogrel, is generally recommended long term in CCS patients withobstructive atherosclerotic CAD. For high-thrombotic-risk CCS patients, long-term therapy with two antithrombotic agents is reasonable, as long asbleeding risk is not high.

· Among CCS patients with normal LV function andno significant left main or proximal left anterior descending lesions, current evidence indicates that myocardial revascularization over GDMT alone does notprolong overall survival.

· Among patients with complex multivessel CADwithout left main CAD, particularly in the presence of diabetes, who are clinically and anatomically suitable for both revascularization modalities, current evidence indicates longer overall survival after coronary artery bypass grafting than percutaneous coronary intervention.

· Lifestyle and risk factor modification combinedwith disease-modifying and antianginal medications are cornerstones in the management of CCS. Furthermore, shared decision making between patients and health care professionals, based on patient-centered care, is paramount in defining the appropriate therapeutic pathway for CCS patients. Patient education is key to improve risk factor control in the long term.

View Details

Ticagrelor monotherapy in ST-elevation myocardial infarction: An individual patient-level meta-analysis from TICO and T-PASS trials

Med. 2024 Aug 10:S2666-6340(24)00301-5.doi: 10.1016/j.medj.2024.07.019.

Abstract

Background: Patients with ST-elevation myocardial infarction (STEMI) tend to be excluded or under-represented in randomized clinical trials evaluating the effects of potent P2Y12 inhibitor monotherapy after short-term dual antiplatelet therapy (DAPT).

Methods: Individual patient data were pooled from randomized clinical trials that included ST-elevation myocardial infarction STEMI patients undergoing drug-eluting stent (DES) implantation and compared ticagrelor monotherapy after short-term (≤3 months) short-termdual antiplatelet therapy versus ticagrelor-based 12-month short-term dual antiplatelet therapy DAPT in terms of centrally adjudicated clinical outcomes. Theco-primary outcomes were efficacy outcome (composite of all-cause death, myocardial infarction, or stroke) and safety outcome (Bleeding AcademicResearch Consortium type 3 or 5 bleeding) at 1 year.

Findings: The pooled cohort contained 2,253 patients with ST-elevation myocardial infarction. The incidence of the primary efficacy outcome did not differ between the ticagrelor monotherapy group and the ticagrelor-based dual antiplatelet therapy group (1.8% versus 2.0%; hazard ratio [HR] = 0.88; 95% confidence interval [CI] = 0.49-1.61; p = 0.684). There was no difference in cardiac death between the groups (0.6% versus 0.7%; HR = 0.89; 95% CI = 0.32-2.46; p = 0.822). The incidence of the primary safety outcome was significantly lower in the ticagrelor monotherapy group (2.3% versus 4.0%;HR = 0.56; 95% CI = 0.35-0.92; p = 0.020). No heterogeneity of treatment effects was observed for the primary outcomes across subgroups.

Conclusions: In patients with ST-elevationmyocardial infarction treated with drug-eluting stent implantation, ticagrelor monotherapy after short-term DAPT was associated with lower major bleeding without an increase in the risk of ischemic events compared with ticagrelor-based 12-month DAPT. Further research is necessary to extend these findings to non-Asian patients.

Disclaimer:

Lupin makes norepresentation or warranty of any kind, expressed or implied, regarding theaccuracy, adequacy, validity, reliability, availability, or completeness of anyscientific information shared by the HCP on the STAR UPDATE podcast. Youshould not allow the contents of this to substitute for your own medicaljudgment, which you should exercise in evaluating the information on thiswebsite.

View Details

Eligibility and Projected Benefits ofRapid Initiation of Quadruple Therapy for Newly Diagnosed Heart Failure

JACC Heart Fail. 2024 Aug;12(8):1365-1377. doi: 10.1016/j.jchf.2024.03.001.

Abstract

Background: U.S. nationwide estimates of the proportion of patients newly diagnosed with heart failure with reduced ejection fraction (HFrEF) eligible for quadruple medical therapy, and the associated benefits of rapid implementation, are not well characterized.

Objectives: This study sought to characterize the degree to which patients newly diagnosed with heart failure with reduced ejection fraction (HFrEF) are eligible for quadruple medical therapy, and the projected benefits of in-hospital initiation.

Methods: Among patients hospitalizedfor newly diagnosed heart failure with reduced ejection fraction (HFrEF) in the Get With The Guidelines-Heart Failure registry from 2016 to 2023, eligibilitycriteria based on regulatory labeling, guidelines, and expert consensus documents were applied for angiotensin receptor-neprilysin inhibitor, beta-blocker, mineralocorticoid receptor antagonist, and sodium-glucose cotransporter 2 inhibitor therapies. Of those eligible, the projected effect of quadruple therapy on 12-month mortality was modeled using treatment effectsfrom pivotal clinical trials utilized by the American HeartAssociation/American College of Cardiology /HFSA Guideline for the Management of Heart Failure, and compared with observed outcomes among patients treated with angiotensin-converting enzyme inhibitor/angiotensin receptor blocker andbeta-blockers.

Results: Of 33,036 patients newly diagnosed with heart failure with reduced ejection fraction (HFrEF), 27,158(82%) were eligible for quadruple therapy, and 30,613 (93%) were eligible for ≥3 components. From 2021 to 2023, of patients eligible for quadruple therapy,15.3% were prescribed quadruple therapy and 41.5% were prescribed triple therapy. Among Medicare beneficiaries eligible for quadruple therapy, 12-monthincidence of mortality was 24.7% and Heart Failure hospitalization was 22.2%. Applying the relative risk reductions in clinical trials, complete implementation of quadruple therapy by time of discharge was projected to yield absolute risk reductions in 12-month mortality of 10.4% (number needed to treat = 10) compared with angiotensin-converting enzyme inhibitor/angiotensinreceptor blocker and beta-blocker, and 24.8% (number needed to treat = 4) compared with no guideline-directed medical therapy.

Conclusions: In this nationwide U.S. cohort of patients hospitalized for newly diagnosed heart failure with reduced ejection fraction (HFrEF), >4 of 5 patients were projected as eligible for quadruple therapy at discharge; yet, <1 in 6 were prescribed it. If clinical trial benefits can be fully realized, in-hospital initiation of quadruplemedical therapy for newly diagnosed heart failure with reduced ejection fraction (HFrEF) would yield large absolute reductions in mortality.

Disclaimer:

View Details

Efficacy and Safety of P2Y12 monotherapy vs DAPT in patients undergoing percutaneous coronary intervention: meta-analysis of randomized trials

Curr Probl Cardiol. 2024 Aug;49(8):102635. doi: 10.1016/j.cpcardiol.2024.102635

Abstract

Background: Debates persist regarding the optimal duration of dual antiplatelet therapy (DAPT) afterpercutaneous coronary intervention (PCI) in coronary artery disease (CAD). Recent trials have introduced a novel approach involving P2Y12 inhibitor monotherapy with ticagrelor or clopidogrel, after a short dual antiplatelet therapy (DAPT). However, the effectiveness and safety of this strategy remains to be established. We aimed to perform a meta-analysis comparing monotherapy with P2Y12 inhibitors versus standard dual antiplatelet therapy DAPT in patients undergoing percutaneous coronary intervention PCI at 12 months.

Methods: Multiple databases were searched. Six RCTs with a total of 24877 patients were included. The primary endpoint was all-cause mortality at 12 months of follow-up. The secondary endpoints were cardiovascular mortality, myocardial infarction, probable or definitestent thrombosis, stroke events, and major bleeding. The study is registered with PROSPERO (CRD42024499529).

Results: Monotherapy with P2Y12 inhibitor ticagrelor significantly reduced both all cause mortality (HR 0.71, 95 CI [0.55-0.91], P = 0.007) and cardiovascular mortality (HR 0.66, 95% CI [0.49-0.89], P = 0.006) compared to standard dual antiplatelet therapy DAPT. In contrast, clopidogrel monotherapy did not demonstrate a similar reduction. The decrease in mortality associated with ticagrelor was primarily due to a lower risk ofmajor bleeding (HR 0.56, 95% CI [0.43-0.72], P < 0.001), while the risk of myocardial infarction (MI) remained unchanged (HR 0.90, 95% CI [0.73-1.11], P = 0.32). The risk of stroke was found to be similar across treatments.

Conclusions: In comparison to standard dual antiplatelet therapy DAPT, P2Y12 inhibitor monotherapy with ticagrelor may lead to a reduced mortality. The clinical benefits are driven by a reduction of bleeding risk without ischemic risk trade-off.

Disclaimer:

View Details

Early postoperative beta-blockers are associated with improved cardiac output after late complete repair of tetralogy of Fallot: a retrospective cohort study

Eur J Pediatr. 2024 Aug;183(8):3309-3317. doi: 10.1007/s00431-024-05597-1.

Abstract

Tetralogy of Fallot is the most common cyanotic congenital heart disease. For decades, our institution has cared for humanitarian patients with late presentation of tetralogy of Fallot. They are characterized by severe right ventricular hypertrophy with consecutive diastolic dysfunction, increasing the risk of postoperative low cardiac output syndrome (LCOS). By right ventricular restrictive physiology, we hypothesized that patients receiving early postoperative beta-blockers (within 48 h after cardiopulmonary bypass) may have better diastolic function and cardiac output. This is a retrospective cohort study in a single-center tertiary pediatricintensive care unit. We included > 1-year-old humanitarian patients with a confirmed diagnosis of tetralogy of Fallot undergoing a complete surgicalrepair between 2005 and 2019. We measured demographic data, preoperative echocardiographic and cardiac catheterization measures, postoperative mean heart rate, vasoactive-inotropic scores, low cardiac output syndrome scores, length of stay, and mechanical ventilation duration. One hundred sixty-five patientsmet the inclusion criteria. Fifty-nine patients (36%) received early postoperative beta-blockers, associated with a lower mean heart rate, higher vasoactive-inotropic scores, and lower low cardiac output syndrome scoresduring the first 48 h following cardiopulmonary bypass. There was no significant difference in lengths of stay and ventilation.

Conclusion: Early postoperative beta-blockers lower the prevalence of postoperative low cardiac output syndrome at the expense of a higher need for vasoactive drugs without any consequence on length of stay and ventilation duration. This approach may benefit the specific population of children undergoing a late complete repair of tetralogy of Fallot.

What is Known: • Prevalence of low cardiacoutput syndrome is high following a late complete surgical repair of tetralogyof Fallot.

What is New: • Early postoperative beta-blockade is associated with lower heart rate, prolonged relaxation time, and lower prevalence of low cardiac output syndrome. • Negative chronotropic agents like beta-blockers may benefit selected patients undergoing a latecomplete repair of tetralogy of Fallot, who are numerous in low-income countries.

Disclaimer:

View Details

Non-ST-elevation acute coronary syndromeswith previous coronary artery bypass grafting: a meta-analysis of invasive vs. conservative management

Eur Heart J . 2024 Jul 12;45(27):2380-2391.doi: 10.1093/eurheartj/ehae245

Abstract

Background and aims: A routine invasive strategy is recommended in the management of higher risk patients with non-ST-elevation acute coronary syndromes (NSTE-ACSs). However, patients with previous coronary artery bypass graft (CABG) surgery were excluded from key trials that informed these guidelines. Thus, the benefit of a routine invasive strategy is less certain in this specific subgroup.

Methods: A systematic review and meta-analysis of randomized controlled trials (RCTs) was conducted. A comprehensive search was performed of PubMed, EMBASE , Cochrane, and ClinicalTrials.gov. Eligible studies were randomized controlled trials of routine invasive vs. a conservative or selective invasive strategy in patients presenting with non-ST-elevation acute coronary syndromes that included patients with previous coronary artery bypass graft. Summary data werecollected from the authors of each trial if not previously published. Outcomes assessed were all-cause mortality, cardiac mortality, myocardial infarction, and cardiac-related hospitalization. Using a random-effects model, risk ratios (RRs) with 95% confidence intervals (CIs) were calculated.

Results: Summary data were obtained from 11 randomized controlled trials, including previously unpublished subgroup outcomes of nine trials, comprising 897 patients with previous CABG (477routine invasive, 420 conservative/selective invasive) followed up for a weighted mean of 2.0 (range 0.5-10) years. A routine invasive strategy did not reduce all-cause mortality (RR 1.12, 95% CI 0.97-1.29), cardiac mortality (RR 1.05, 95% CI 0.70-1.58), myocardial infarction (RR 0.90, 95% CI 0.65-1.23), or cardiac-related hospitalization (RR 1.05, 95% CI 0.78-1.40).

Conclusions: This is the first meta-analysis assessing the effect of a routine invasive strategy in patientswith prior coronary artery bypass graft who present with non-ST-elevation acute coronary syndromes. The results confirm the under-representation of this patient group in randomized controlled trials of invasive management in non-ST-elevation acute coronary syndromes and suggest that there is no benefit to a routine invasive strategy compared to a conservative approach with regard to major adverse cardiac events. These findings should be validated in an adequately powered randomized controlled trial.

Disclaimer:

View Details

Verification of haemoglobin level to prevent worsening of prognosis in heart failure with preserved ejection fraction patients from the PURSUIT-HFpEF registry

https://doi.org/10.1002/ehf2.14927

Abstract

Aim

Anaemia has been reported as poor predictorin heart failure with preserved ejection fraction (HFpEF). The aim of this study was to evaluate the impact of changes in haemoglobin (Hb) from dischargeto 1 year after discharge on the prognosis using a lower cut-off value of Hb than the World Health Organization (WHO) criteria.

Methods and results

First, 547 heart failure with preserved ejection fraction cases were divided into two groups, Hb < 11.0 g/dL (n= 218) and Hb ≥ 11.0 g/dL (n = 329), according to Hbat discharge, and further were divided according to Hb 1 year after discharge into Hb < 11.0 g/dL (G1, n = 113), Hb ≥ 11.0 g/dL (G2, n = 105), Hb < 11.0 g/dL (G3, n = 66), and Hb ≥ 11.0 g/dL (G4, n = 263), respectively. Major adverse cardiovascular events (MACE) was defined as composite of all-cause death and heart failure readmission after a visit 1 year after discharge. The cut-off value of Hb was analysed by the receiver operating characteristics curvethat predicts Major adverse cardiovascular events. We examined the incidence rate of Major adverse cardiovascular events between G4 and other subgroups and verified predictors of improving or worsening anaemia and covarying factors with change in Hb.In multivariate Cox proportional hazard model, MACE was significantly higher in G3 with worsening anaemia from Hb ≥ 11.0 g/dL to <11.0 g/dL than G4 with persistently Hb ≥ 11 g/dL (adjusted hazard ratio (HR):3.14 [95% confidence interval (CI), 1.76–5.60], P < 0.001). Major adverse cardiovascular events was not significantly different between G2 with improving anaemia from Hb< 11.0 g/dL to ≥ 11.0 g/dL andG4 (adjusted HR: 1.37 [95%CI, 0.68–2.75], P = 0.38). In multivariate logistic regression analysis, independent predictors of improving anaemia were male [odds ratio (OR): 0.45], chronicobstructive pulmonary disease (OR: 10.3), prior heart failure hospitalization (OR: 0.38), and estimated glomerular filtration rate (OR: 1.04). Independent predictors of worsening anaemia were age (OR:1.07), body mass index (BMI) (OR: 0.86), clinical frailty scale score (OR: 1.29), Hb at discharge (OR: 0.63), and use of angiotensin-converting-enzyme inhibitor or angiotensin II receptor blocker (OR: 2.76). Inmultivariate linear regression analysis, covarying factors with change in Hb were BMI (β = −0.098), serum albumin (β = 0.411), and total cholesterol (β = 0.179).

Conclusions

Change in haemoglobin after discharge using alower cut-off value than World Health Organization criteria has prognostic impact in patients with heart failure with preserved ejection fraction.

Disclaimer:

View Details

Ticagrelor downregulates the expressionof proatherogenic and proinflammatory micro RNA 125-b compared to clopidogrel: A randomized, controlledtrial

Int J Cardiol . 2024 Jul 1:406:132073

Abstract

Background: Platelet P2Y12 antagonist ticagrelor reduces cardiovascular mortality after acute myocardialinfarction (AMI) compared to clopidogrel, but the underlying mechanism is unknown. Because activated platelets release proatherogenic and proinflammatorymicroRNAs, including microRNA -125a, microRNA -125b and microRNA-223, we hypothesized that the expression of these miRNAs is lower on ticagrelor, compared to clopidogrel.

Objectives: We compared miR -125a, miR-125b and miR-223 expression in plasma of patients after AMI treated with ticagrelor or clopidogrel.

Methods: After percutaneous coronaryintervention on acetylsalicylic acid and clopidogrel, 60 patients with first AMI were randomized to switch to ticagrelor or to continue with clopidogrel.Plasma expression of miR-223, miR-125a-5p, miR-125b was measured using quantitative polymerase chain reaction at baseline and after 72 h and 6 monthsof treatment with ticagrelor or clopidogrel in patients and one in 30 healthy volunteers. Multiple electrode aggregometry using ADP test was used to determineplatelet reactivity in response to P2Y12 inhibitors.

Results: Expression of miR-125b was higher inpatients with AMI 72 h and 6 months, compared to healthy volunteers (p =0.001), whereas expression of miR-125a-5p and miR-223 were comparable. In patients randomized to ticagrelor, expression of miR-125b decreased at 72 h (p = 0.007) and increased back to baseline at 6 months (p = 0.005). Expression of miR-125a-5p and miR-223 was not affected by the switch from clopidogrel to ticagrelor.

Conclusions: Ticagrelor treatment leads to lower plasma expression of miR-125b after acute myocardial infarction, compared to clopidogrel. Higher expression of miR-125b might explain recurrent thrombotic events and worse clinical outcomes in patients treated with clopidogrel, compared to ticagrelor.

Disclaimer:

View Details

Clinical Pharmacogenetics ImplementationConsortium Guideline (CPIC) for CYP2D6, ADRB1,ADRB2, ADRA2C, GRK4, and GRK5 Genotypes and Beta-Blocker Therapy

Clin Pharmacol Ther. 2024 Jul 1. doi: 10.1002/cpt.3351

Abstract

Beta-blockers are widely used medications fora variety of indications, including heart failure, myocardial infarction, cardiac arrhythmias, and hypertension. Genetic variability in pharmacokinetic(e.g., CYP2D6) and pharmacodynamic (e.g., ADRB1, ADRB2, ADRA2C, GRK4, GRK5) genes have been studied in relation to beta-blocker exposure and response. Wesearched and summarized the strength of the evidence linking beta-blocker exposure and response with the six genes listed above. The level of evidence was high for associations between CYP2D6 genetic variation and both metoprolol exposure and heart rate response. Evidence indicates that CYP2D6 poor metabolizers experience clinically significant greater exposure and lower heart rate in response to metoprolol compared with those who are not poor metabolizers. Therefore, we provide therapeutic recommendations regardinggenetically predicted CYP2D6 metabolizer status and metoprolol therapy. However, there was insufficient evidence to make therapeutic recommendationsfor CYP2D6 and other beta-blockers or for any beta-blocker and the other five genes evaluated.

Disclaimer:

View Details

The new ESC acute coronary syndrome guideline and its impact in the CPU and emergency department setting

Herz. 2024 Jun;49(3):185-189. doi: 10.1007/s00059-024-05241-6

The new guideline on acute coronary syndrome (ACS) of the European Society of Cardiology (ESC) replaces twoseparate guidelines on ST-elevation myocardial infarction (STEMI) and non-ST-elevation (NSTE) ACS . This change of paradigm reflects the experts view that the acute coronary syndrome is a continuum,starting with unstable angina and ending in cardiogenic shock or cardiac arrest due to severe myocardial ischemia. Secondary, partly non-atherosclerotic-causedmyocardial infarctions ("type 2") are not integrated in this concept. With respect to acute care in the setting of emergency medicine and the chest pain unit structures, the following new aspects have to be taken into account:

New procedural approach as "think acute coronary syndrome" meaning "abnormal ECG," "clinicalcontext," and "stable patient"
New recommendation regarding a holistic approach for frail patients
Revised recommendations regardingimaging and timing of invasive strategy in suspected non-ST elevation acute coronary syndrome.

4- Revised recommendations for antiplatelet and anticoagulant therapy in ST-elevation myocardial infarction

Revised recommendations for cardiac arrest and out-of-hospital cardiac arrest
Revised recommendations for in-hospital management (starting in the CPU/ED ) and acute coronary syndrome comorbid conditions.

In summary, the changes are mostly gradualand are not based on extensive new evidence, but more on focused and healthcare process-related considerations.

Disclaimer:

View Details

Ticagrelor with or without aspirin following percutaneous coronary intervention in high-risk patients with concomitant peripheral artery disease: A subgroup analysis of the TWILIGHT randomized clinical trial

Am Heart J. 2024 Jun:272:11-22. doi:10.1016/j.ahj.2024.03.002

Abstract

Background: The optimal antiplateletregimen after percutaneous coronary intervention (PCI) in patients with peripheral artery disease (PAD) is still debated. This analysis aimed to compare the effect of ticagrelor monotherapy versus ticagrelor plus aspirin in patients with peripheral artery disease undergoing percutaneous coronary intervention.

Methods: In the TWILIGHT trial, patients at high ischemic or bleeding risk that underwent percutaneous coronary intervention were randomized after 3 months of dual antiplatelet therapy (DAPT) to aspirin or matching placebo in addition to open-label ticagrelor for 12 additional months. In this post-hoc analysis, patient cohorts were examined according to the presence or absence of peripheral artery disease. The primary endpoint was Bleeding Academic Research Consortium (BARC) 2, 3, or 5 bleeding. The key secondary endpoint was a composite of all-cause death, myocardial infarction (MI), or stroke. Endpoints were assessed at 12 months after randomization.

Results: Among 7,119 patients, 489 (7%) had peripheral artery disease and were older, more likely to havecomorbidities, and multivessel disease. Peripheral artery disease patients had more bleeding or ischemic complications than no- peripheral artery diseasepatients. Ticagrelor monotherapy compared to ticagrelor plus aspirin was associated with less BARC 2, 3, or 5 bleeding in peripheral artery disease (4.6% vs 8.7%; HR 0.52; 95%Cl 0.25-1.07) and no- peripheralartery disease patients (4.0% vs 7.0%; HR 0.56; 95%CI 0.45-0.69; interaction P-value .830) and a similar risk of death, myocardial infarction, or stroke in these 2 groups (interaction P-value .446).

Conclusions: Despite their higher ischemicand bleeding risk, patients with Peripheral artery disease undergoing percutaneous coronary intervention derived a consistent benefit from ticagrelor monotherapy after 3 months of dual antiplatelet therapy in terms of bleedingreduction without any relevant increase in ischemic events.

Disclaimer:

View Details

Antiplatelet therapy after coronary artery bypass surgery: five year follow-up of randomised Different Antiplatelet Therapy Strategy After Coronary Artery Bypass Grafting trial

BMJ . 2024 Jun 11:385:e075707. doi:10.1136/bmj-2023-075707.

Abstract

Objective: To assess the effect ofdifferent antiplatelet strategies on clinical outcomes after coronary artery bypass grafting.

Design: Five year follow-up of randomised Different Antiplatelet Therapy Strategy After Coronary Artery Bypass Grafting (DACAB) trial.

Setting: Six tertiary hospitals in China; enrolment between July 2014 and November 2015; completion of five-year follow-up from August 2019 to June 2021.

Participants: 500 patients aged 18-80 years (including 91 (18.2%) women) who had elective coronary arterybypass grafting surgery and completed the Different Antiplatelet Therapy Strategy After Coronary Artery Bypass Grafting trial.

Interventions: Patients wererandomised 1:1:1 to ticagrelor 90 mg twice daily plus aspirin 100 mg once daily (dual antiplatelet therapy; n=168), ticagrelor monotherapy 90 mg twice daily (n=166), or aspirin monotherapy 100 mg once daily (n=166) for one year after surgery. After the first year,antiplatelet therapy was prescribed according to standard of care by treating physicians.

Main outcome measures: The primary outcome was major adverse cardiovascular events (a composite of all cause death, myocardial infarction, stroke, and coronary revascularisation), analysed using the intention-to-treat principle. Time-to-event analysis was used to compare the risk between treatment groups. Multiple post hoc sensitivity analyses examined the robustness of the findings.

Results: Follow-up at five years for major adverse cardiovascular events was completed for 477 (95.4%) of 500 patients; 148 patients had major adverse cardiovascular events, including 39 in the dual antiplatelet therapy group, 54 in the ticagrelor monotherapy group, and 55 in the aspirin monotherapy group. Risk of major adverse cardiovascularevents at five years was significantly lower with dual antiplatelet therapy versus aspirin monotherapy(22.6% v 29.9%; hazard ratio 0.65, 95% confidence interval 0.43 to 0.99; P=0.04) and versus ticagrelor monotherapy (22.6% v 32.9%; 0.66, 0.44 to 1.00; P=0.05). Results were consistent in all sensitivity analyses.

Conclusions: Treatment with ticagrelor dual antiplatelet therapy for one year after surgery reduced the risk of major adverse cardiovascular events at five years after coronary artery bypass grafting compared with aspirin monotherapy or ticagrelor monotherapy.

Disclaimer:

View Details

Coronary Atherosclerotic Plaque Activity and Risk of Myocardial Infarction

J Am Coll Cardiol. 2024 Jun 4;83(22):2135-2144

Abstract

Background: Total coronaryatherosclerotic plaque activity across the entire coronary arterial tree is associated with patient-level clinical outcomes.

Objectives: We aimed to investigatewhether vessel-level coronary atherosclerotic plaque activity is associated with vessel-level myocardial infarction.

Methods: In this secondary analysisof an international multicenter study of patients with recent myocardial infarction and multivessel coronary artery disease, we assessed vessel-level coronary atherosclerotic plaque activity using coronary 18F-sodium fluoride positron emission tomography to identify vessel-level myocardial infarction.

Results: Increased 18F-sodium fluoride uptake was found in 679 of 2,094 coronary arteries and 414 of 691patients. Myocardial infarction occurred in 24 (4%) vessels with increased coronary atherosclerotic plaque activity and in 25 (2%) vessels without increased coronary atherosclerotic plaque activity (HR: 2.08; 95% CI: 1.16-3.72; P = 0.013). This association was not demonstrable in those treated with coronaryrevascularization (HR: 1.02; 95% CI: 0.47-2.25) but was notable in untreated vessels (HR: 3.86; 95% CI: 1.63-9.10;Pinteraction = 0.024). Increased coronary atherosclerotic plaque activity in multiple coronary arteries was associated with heightened patient-level risk of cardiac death or myocardial infarction (HR: 2.43; 95% CI: 1.37-4.30; P = 0.002) as well as first (HR: 2.19; 95% CI: 1.18-4.06; P = 0.013) and total (HR: 2.50; 95% CI: 1.42-4.39; P = 0.002) myocardial infarctions.

Conclusions: In patients with recentmyocardial infarction and multivessel coronary artery disease, coronary atherosclerotic plaque activity prognosticates individual coronary arteries and patients at risk for myocardial infarction.

Disclaimer:

View Details

Management of Severe Mitral Regurgitation in Patients With Acute Myocardial Infarction: JACC Focus Seminar 2/5

J Am Coll Cardiol . 2024 May 7;83(18):1799-1817. doi:10.1016/j.jacc.2023.09.840

Abstract

Severe acute mitral regurgitation after myocardialinfarction includes partial and complete papillary muscle rupture or functional mitral regurgitation. Although its incidence is <1%, mitral regurgitation after acute myocardial infarction frequently causes hemodynamic instability, pulmonary edema, and cardiogenic shock. Medical management has the worst prognosis, and mortality has not changed in decades. Surgery represents the gold standard, but it is associated with high rates of morbidity and mortality. Recently, transcatheter interventions have opened a new door for management that may improve survival. Mechanical circulatory support restores vital organ perfusion and offers the opportunity for a steadier surgical repair. Thisreview focuses on the diagnosis and the interventional management, both surgical and transcatheter, with a glance on future perspectives to enhance patientmanagement and eventually decrease mortality.

Disclaimer:

View Details

Tolerability and effectiveness of beta-blockers in patients with cardiac amyloidosis: A systematic review and meta-analysis

Int J Cardiol . 2024 May 1:402:131813. doi:10.1016/j.ijcard.2024.131813

Abstract

Objective: This systematic review aimed to assess thetolerability of patients with cardiac amyloidosis (CA) to beta-blockers (BBs) and evaluate its association with adverse outcomes.

Methods: We performed a comprehensive search fromJanuary 1, 2000 to October 20, 2023. Studies examining BB use and tolerance or the relationship between BB use and outcomes in patients with CA were included. Pooled adjusted hazard ratios (aHRs) for all-cause mortality were calculated using random- and fixed-effects models.

Results: Eight observational studies involving 4002patients with CA (87.5% with transthyretin CA [ATTR-CA] and 12.5% with immunoglobulin light chain CA [AL-CA]) were assessed. BBs were used by 52.5% of the patients.However, 26.3% of the patients discontinued BBs because of hypotension, bradycardia, or fatigue. Regarding the association between BB use and all-causedeath, four studies were identified that included 2874 patients with ATTR-CA and 16 patients with AL-CA. The meta-analysis revealed no apparent relationship between BB use and all-cause mortality (pooled aHR = 0.78, 95% confidence interval (CI) = 0.40-1.51). Two studies on patients with ATTR-CA found no impact of BB use on all-cause mortality in the subgroup with left ventricular ejection fraction (LVEF) > 40%, but conflicting results exist for those with LVEF ≤40% (pooled aHR = 0.78, 95% CI = 0.40-1.54).

Conclusion: The limited number of observationalstudies that predominantly enrolled patients with ATTR -CA showed that BBs were used in almost half of the patients with CA, with varying tolerability. However, no significant association was observed between BB use and all-cause mortality.

Disclaimer:

View Details

Ticagrelor alone versus ticagrelor plus aspirin from month 1 to month 12 after percutaneous coronary intervention in patients with acute coronary syndromes (ULTIMATE-DAPT): a randomized, placebo-controlled, double-blind clinical trial

Randomized Controlled Trial Lancet . 2024 May 11;403(10439):1866-1878. doi: 10.1016/S0140-6736(24)00473-2.

Abstract

Background: Following percutaneous coronaryintervention with stent placement to treat acute coronary syndromes, international clinical guidelines generally recommend dual antiplatelet therapywith aspirin plus a P2Y12 receptor inhibitor for 12 months to prevent myocardial infarction and stent thrombosis. However, data on single antiplatelet therapy with a potent P2Y12 inhibitor earlier than 12 months afterpercutaneous coronary intervention for patients with an acute coronary syndrome are scarce. The aim of this trial was to assess whether the use of ticagrelor alone, compared with ticagrelor plus aspirin, could reduce the incidence of clinically relevant bleeding events without an accompanying increase in major adverse cardiovascular or cerebrovascular events (MACCE).

Methods: In this randomized, placebo-controlled,double-blind clinical trial, patients aged 18 years or older with an acute coronary syndrome who completed the IVUS-ACS study and who had no major ischaemic orbleeding events after 1-month treatment with dual antiplatelet therapy were randomly assigned to receive oral ticagrelor (90 mg twice daily) plus oral aspirin (100 mg once daily) or oral ticagrelor (90 mg twice daily) plus a matching oral placebo, beginning 1 month and ending at 12 months after percutaneous coronary intervention (11 months in total). Recruitment took place at 58 centres in China, Italy, Pakistan, and the UK. Patients were required to remain event-free for 1 month on dual antiplatelet therapy following percutaneous coronary intervention with contemporary drug-eluting stents.Randomisation was done using a web-based system, stratified by acute coronary syndrome type, diabetes, IVUS-ACS randomisation, and site, using dynamicminimisation. The primary superiority endpoint was clinically relevant bleeding (Bleeding Academic Research Consortium [known as BARC] types 2, 3, or 5). Theprimary non-inferiority endpoint was MACCE (defined as the composite of cardiac death, myocardial infarction, ischaemic stroke, definite stent thrombosis, orclinically driven target vessel revascularisation), with an expected event rate of 6·2% in the ticagrelor plus aspirin group and an absolute non-inferiority margin of 2·5 percentage points between 1 month and 12 months afterpercutaneous coronary intervention. The two co-primary endpoints were tested sequentially; the primary superiority endpoint had to be met for hypothesistesting of the MACCE outcome to proceed. All principal analyses were assessed in the intention-to-treat population.

Findings: Between Sept 21, 2019, and Oct 27, 2022, 3400 (97·0%) of the 3505 participants in the IVUS-ACS study were randomly assigned (1700 patients toticagrelor plus aspirin and 1700 patients to ticagrelor plus placebo). 12-month follow-up was completed by 3399 (>99·9%) patients. Between month 1 and month 12 after percutaneous coronary intervention, clinically relevant bleeding occurred in 35 patients (2·1%) inthe ticagrelor plus placebo group and in 78 patients (4·6%) in the ticagrelor plus aspirin group (hazard ratio [HR] 0·45 [95% CI 0·30 to 0·66]; p<0·0001). MACCE occurred in 61 patients (3·6%) in the ticagrelor plus placebo group and in 63 patients (3·7%) in the ticagrelor plus aspirin group (absolute difference -0·1% [95% CI -1·4% to 1·2%]; HR 0·98 [95% CI 0·69 to 1·39];pnon-inferiority<0·0001, psuperiority=0·89).

Interpretation: In patients with an acute coronary syndrome who had percutaneous coronary intervention with contemporary drug-eluting stents and remained event-free for 1 month on dual antiplatelet therapy,treatment with ticagrelor alone between month 1 and month 12 after the intervention resulted in a lower rate of clinically relevant bleeding and a similar rate of MACCE compared with ticagrelor plus aspirin. Along with the results from previous studies, these findings show that most patients in this population can benefit from superior clinical outcomes with aspirin discontinuation and maintenance on ticagrelor monotherapy after 1 month of dual antiplatelet therapy.

Disclaimer:

View Details

Obesity is associated with acute kidney injury in ST-segment-elevation myocardial infarction undergoing percutaneous coronary intervention: A national representative cohort study

Catheter Cardiovasc Interv . 2024 May;103(6):897-908. doi: 10.1002/ccd.31030

Abstract

Background: Acute kidney injury (AKI) is a frequentand potentially life-threatening complication after percutaneous coronary intervention (PCI) in patients with ST-segment-elevation myocardial infarction(STEMI). However, the relationship between obesity and the risk of AKI in this specific patient population has not been previously examined.

Methods: We queried the National Inpatient Sample(2016-2019) using ICD-10 codes to obtain a sample of adults with STEMI undergoing PCI. All patients were further subcategorized into obese and nonobese cohorts. The primary outcome was the incidence of AKI. Multivariate regression analysis was performed to assess the impact of obesity on AKI. The consistency of this correlation between subgroups was investigated usingsubgroup analysis and interaction testing.

Results: A total of 62,599 (weighted nationalestimate of 529,016) patients were identified, of which 9.80% (n = 6137) had AKI. Obesity comprised 19.78% (n = 1214) of the AKI cohort. Obese patients wereon average younger, male, white, and had more comorbidities. Additionally, there was a significant positive association between obesity and AKI incidence(adjusted odds ratio [aOR]: 1.24, 95% confidence interval [CI]: 1.15-1.34), which was more pronounced in female patients (aOR: 1.56, 95% CI: 1.33-1.82, p < 0.001, p-interaction = 0.008). The AKI incidence in these patientsincreased steadily during the 4-year study period, and it was consistently higher in obese patients than in nonobese patients (p-trend < 0.001 for all).

Conclusions: Obesity was independently associatedwith a greater risk of AKI among adults with STEMI undergoing PCI, particularly in female patients.

Disclaimer:

Lupin makes no representation or warranty of any kind, expressed or implied, regarding theaccuracy, adequacy, validity, reliability, availability, or completeness of any scientific information shared by the HCP on the STAR UPDATE podcast. Youshould not allow the contents of this to substitute for your own medical judgment, which you should exercise in evaluating the information on this website.

View Details

The application value of Metoprolol combined with Dagalizin in enhancing cardiac function and ventricularremodeling in patients with acute myocardial infarction after percutaneous coronary intervention.

J Clin Emerg, 2024, 25(4): 170-174. doi:10.13201/j.issn.1009-5918.2024.04.003

Abstract

To discuss the application value of metoprolol combined with daglizin in improving cardiac function and ventricular remodeling in patients with acute myocardial infarction(AMI) after percutaneous coronary intervention(PCI).

A total of 86 patients with acute myocardial infarction I- percutaneous coronary intervention from January 2022 to October 2023 were selected and divided into experimental group(43 cases) and control group(43 cases) according to a random table. Patients in the control group were given metoprolol + conventional treatment and patients in the experimental group were given combined treatment with daglizin on this basis. The cardiac function(left ejection fraction[LVEF], heart index[CI], stroke output[SV]), ventricular remodeling(left ventricular end-diastolic volume[LVEDV], left ventricularend-systolic volume[LVESV], left ventricular end-diastolic diameter[LVEDD]) and laboratory parameters(N-terminal B-type natriuretic peptideprecursor[NT-proBNP], hypersensitive C-reactive protein[hs-CRP], interleukin-6[IL-6]), adverse cardiovascular events and adverse events were compared between the two groups.

After treatment, the left ejection fraction, heart index and stroke output of the two groups were significantly higher than those before treatment, and the left ejection fraction, heart index and stroke output in the experimental group were significantly higher than those in the control group(P < 0.05). After treatment, the Left ventricular end-diastolic volume, left ventricular end-systolic volume, left ventricular end-diastolic diameter,N-terminal B-type natriuretic peptide precursor, hypersensitive C-reactive protein and interleukin-6of the two groups were significantly lower than those before treatment, and Left ventricular end-diastolic volume, left ventricular end-systolic volume, leftventricular end-diastolic diameter, N-terminal B-type natriuretic peptide precursor, hypersensitive C-reactive protein and interleukin-6in the experimental group were significantly lower than those in the control group(P < 0.05). The incidence of adverse cardiovascular events in the experimental group was significantly lower than that in the control group(P < 0.05). The adverse events rate of the two groups was basically the same(P>0.05).

Metoprolol combined with daglizin can improve cardiacfunction and ventricular remodeling in patients with acute myocardial infarction (AMI) after percutaneous coronary intervention(PCI), which is beneficial for prognosis improvement, and it is worthy of clinical promotion.

Disclaimer:

Lupin makes no representation or warranty of any kind, expressed or implied, regarding the accuracy, adequacy,validity, reliability, availability, or completeness of any scientific information shared by the HCP on the STAR UPDATE podcast. You should not allow the contents of this to substitute for your own medical judgment, whichyou should exercise in evaluating the information on this website

View Details

Prognostic Impact of Early Administration of β-Blockers in Critically Ill Patients with Acute Myocardial Infarction

J Clin Pharmacol . 2024 Apr;64(4):410-417.doi: 10.1002/jcph.2370.

Abstract

In critically ill patients with acute myocardialinfarction (AMI), the relationship between the early administration of β-blockers and the risks of in-hospital and long-term mortality remains controversial. Furthermore, there are conflicting evidences for the efficacy of the early administration of intravenous followed by oral β-blockers in acute myocardial infarction. We conducted a retrospective analysis of critically ill patients with acute myocardial infarction who received the early administration of β-blockers within 24 hours of admission. The data were extracted from the Medical Information Mart for Intensive Care IV database. We enrolled 2467 critically ill patients with AMI in the study, with 1355 patients who receivedthe early administration of β-blockers and 1112 patients who were non-users. Kaplan-Meier survival analysis and Cox proportional hazards models showed that the earlyadministration of β-blockers was associated with a lower risk of in-hospital mortality (adjusted hazardratio [aHR] 0.52; 95% confidence interval [95%CI] 0.42-0.64), 1-year mortality (aHR 0.54, 95%CI 0.47-0.63), and 5-year mortality (aHR 0.60, 95%CI0.52-0.69). Furthermore, the early administration of both oral β-blockers and intravenous β-blockers followed by oral β-blockers may reduce the mortality risk, compared with non-users. The risks of in-hospital and long-term mortality were significantly decreased in patients who underwent revascularization with the early administration of β-blockers. We found thatthe early administration of β-blockers could lower the risks of in-hospital and long-term mortality. Furthermore, the early administration of both oral β-blockers and intravenous β-blockers followed by oral β-blockers may reduce the mortality risk, compared with non-users. Notably, patients who underwent revascularization with the early administration of β-blockers showed the lowest risks of in-hospital and long-term mortality.

Disclaimer:

Lupin makes no representation or warranty of any kind, expressed or implied, regarding the accuracy, adequacy,validity, reliability, availability, or completeness of any scientific information shared by the HCP on the STAR UPDATE podcast. You should not allow the contents of this to substitute for your own medical judgment, whichyou should exercise in evaluating the information on this website

View Details

Ticagrelor was associated with lower fracture risk than clopidogrel in the dual anti-platelet regimen among patients with acute coronary syndrome treated with percutaneous coronary intervention

J Endocrinol Invest. 2024 Apr;47(4):895-902.doi: 10.1007/s40618-023-02205-1

Abstract

Purpose: Patients with coronary artery disease haveincreased fracture risks. P2Y12 inhibitors may impact fracture risks. We compared the fracture risks associated with ticagrelor and clopidogrel in dualanti-platelet therapy (DAPT).

Methods: We identified all adults who underwentfirst-ever percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS) between 2010 and 2017 from a territory-wide PCI registry in Hong Kong.Following 1:1 propensity-score matching for baseline characteristics, patients were followed up till event occurrence, death, or 30 June 2022. Outcomes ofinterest were major osteoporotic fractures (MOF) identified by validated ICD-9-CM codes. Cox proportional hazards regression was used to compute the hazard ratio (HR) for major osteoporotic fractures associated with ticagrelor versus clopidogrel use.

Results: 3018 ticagrelor users and 3018 clopidogrel users were identified after propensity-score matching (mean age: 61.4 years; 84.1% men). Upon median follow-up of 6.5 years, 59 ticagrelor users and 119 clopidogrel users sustained major osteoporotic fractures (annualized fracture risks: 0.34 % and 0.56%, respectively).Ticagrelor use was associated with lower risks of major osteoporotic fractures (HR 0.60, 95%CI 0.44-0.83; p =0.002). Consistent hazard ratios were observed for fractures over vertebrae, hip and upper limbs. Subgroup analyses showed no interaction according to age, sex, presence of diabetes, presence of chronic kidney disease and prior fracture history.

Conclusion: Among adults who underwent first-ever percutaneous coronary intervention for acute coronary syndrome, ticagrelor use in the dual anti-platelet therapy was associated with a lower risk of major osteoporoticfractures compared with clopidogrel. Our results support the use of ticagrelor in the dual anti-platelet therapy from the perspective of bone health.

Disclaimer:

Lupin makes no representation or warranty of any kind, expressed or implied, regarding the accuracy, adequacy, validity, reliability, availability, or completeness of any scientific information shared by the HCP on the STARUPDATE podcast. You should not allow the contents of this to substitute for your own medical judgment, which you should exercise in evaluating the informationon this website

View Details

Impact of cardiac rehabilitation on ventricular-arterial coupling and left ventricular function in patients withacute myocardial infarction

PLoS One . 2024 Apr 4;19(4):e0300578. doi:10.1371/journal.pone.0300578

Abstract

To maintain efficient myocardial function, optimalcoordination between ventricular contraction and the arterial system is required. Exercise-based cardiac rehabilitation (CR) has been demonstrated toimprove left ventricular (LV) function. This study aimed to investigate the impact of cardiac rehabilitation on ventricular-arterial coupling (VAC) and its components, as well as their associations with changes in LV function in patients with acute myocardial infarction (AMI) and preserved or mildly reduced ejection fraction (EF). Effective arterial elastance (EA) and index (EAI) werecalculated from the stroke volume and brachial systolic blood pressure. Effective left ventricular end-systolic elastance (ELV) and index (ELVI) were obtained using the single-beat method. The characteristic impedance (Zc) of the aortic root was calculated after Fourier transformation of both aortic pressure and flow waveforms. Pulse wave separation analysis was performed to obtain the reflection magnitude (RM). An exercise-based, outpatient cardiac rehabilitation(CR) program was administered for up to 6 months. Twenty-nine patients were studied. However, eight patients declined to participate in the cardiac rehabilitation program and were subsequently classified as the non- cardiac rehabilitation group. At baseline, E' velocity showed significant associations with EAI (beta -0.393; P = 0.027) and VAC (beta -0.375; P =0.037). There were also significant associations of LV global longitudinal strain (LV GLS) with EAI (beta 0.467;P = 0.011). Follow-up studies after a minimum of 6 months demonstrated a significant increase in E' velocity (P = 0.035), improved EF (P = 0.010), andLV GLS (P = 0.001), and a decreased EAI (P = 0.025) only in the cardiac rehabilitation group. Changes in E' velocitywere significantly associated with changes in EAI (beta -0.424; P = 0.033). Increased aortic afterload and ventricular-arterial mismatch were associated with a negative impact on both left ventricular diastolic and systolic function. The outpatient cardiac rehabilitation program effectively decreased aortic afterload and improved left ventricular diastolic and systolic dysfunction in patients with acute myocardial infarction and preserved or mildly reduced Ejection Fraction.

Disclaimer:

Lupin makes no representation or warranty of any kind, expressed or implied, regarding the accuracy, adequacy,validity, reliability, availability, or completeness of any scientific information shared by the HCP on the STAR UPDATE podcast. You should not allow the contents of this to substitute for your own medical judgment, whichyou should exercise in evaluating the information on this website

View Details

Myocardial infarction drives trainedimmunity of monocytes, accelerating atherosclerosis

Eur Heart J . 2024 Mar 1;45(9):669-684.

Abstract

Background and aims: Survivors of acute coronarysyndromes face an elevated risk of recurrent atherosclerosis-related vascular events despite advanced medical treatments. The underlying causes remainunclear. This study aims to investigate whether myocardial infarction -induced trained immunity in monocytes could sustain proatherogenic traits and expedite atherosclerosis.

Methods: Apolipoprotein-E deficient (ApoE-/-) miceand adoptive bone marrow transfer chimeric mice underwent MI or myocardial ischaemia-reperfusion (IR). A subsequent 12-week high-fat diet (HFD) regimenwas implemented to elucidate the mechanism behind monocyte trained immunity. In addition, classical monocytes were analysed by flow cytometry in the blood of enrolled patients.

Results: In MI and IR mice, blood monocytes and bonemarrow-derived macrophages exhibited elevated spleen tyrosine kinase (SYK), lysine methyltransferase 5A (KMT5A), and CCHC-type zinc finger nucleicacid-binding protein (CNBP) expression upon exposure to a HFD or oxidized LDL (oxLDL) stimulation. MI induced trained immunity was transmissible by transplantation of bone marrow to accelerateatherosclerosis in naive recipients. KMT5A specifically recruited monomethylation of Lys20 of histone H4 (H4K20me) to the gene body of SYK and synergistically transactivated SYK with CNBP. In vivo small interfering RNA (siRNA) inhibition of KMT5A or CNBP potentially slowed post-MI atherosclerosis. Sympathetic denervation with 6-hydroxydopamine reduced atherosclerosis and inflammation after MI. Classical monocytes from STEMI patients withadvanced coronary lesions expressed higher SYK and KMT5A gene levels.

Conclusions: The findings underscore the crucial roleof monocyte trained immunity in accelerated atherosclerosis after myocardial infarction, implying that spleen tyrosine kinase in blood classical monocytesmay serve as a predictive factor for the progression of atherosclerosis in STEMI patients.

Disclaimer:

View Details

The efficacy and safety of aspirin-ticagrelor vs. aspirin-clopidogrel in ischemic stroke patients withcerebral artery stenting

Clin Neurol Neurosurg . 2024 Mar 3:239:108229.

Abstract

Objective: First, the efficacy and safety ofaspirin-ticagrelor after cerebral artery stenting in ischemic stroke patients is controversial. Second, there is a gap in the research on guiding twoantiplatelet therapy after stenting based on the CYP2C19 genotype.

Methods: This retrospective study included patientswho underwent cerebral artery stenting at the First Affiliated Hospital of Chongqing Medical University from January 2019 to February 2023. We dividedthem into the aspirin-clopidogrel group and aspirin-ticagrelor group and carefully collected baseline information laboratory data and imaging resultsfrom the patients. The efficacy outcomes were 30 days recurrent stroke, 90 days recurrent stroke, and 180 days recurrent stroke, and the safety outcome wasintracranial hemorrhage. T-tests or Fisher's tests were performed for study outcomes in both groups of patients.

Outcome: A total of 372 patients were included. Forefficacy outcomes, aspirin-ticagrelor was associated with a reduced risk of 180 days recurrent stroke, in patients with CYP2C19 LOF allele and CYP2C19intermediate metabolic genotype compared with aspirin-clopidogrel. There was no significant difference in the rate of intracranial hemorrhage between patientswith aspirin-clopidogrel and aspirin-ticagrelor, regardless of overall, CYP2C19 LOF allele carriers or CYP2C19 intermediate metabolizer. No significant differences were found between the two on other efficacy and safety outcomes.

Conclusion: A cohort study found that aspirin-ticagrelorwas significantly superior to aspirin-clopidogrel in reducing 180 days recurrent stroke in CYP2C19 LOF allele carriers and CYP2C19 intermediatemetabolizers. There was no significant difference between aspirin-ticagrelor and aspirin-clopidogrel in the risk of intracranial hemorrhage in terms of ICHrates.

Disclaimer:

View Details

Beta-blocker therapy in heart failurewith preserved ejection fraction (B-HFpEF): A systematic review and meta-analysis

Curr Probl Cardiol. 2024 Mar;49(3):102376

Abstract

Introduction: While beta-blockers are considered thecornerstone of treatment for heart failure with reduced ejection fraction, the same may not apply to patients with heart failure with preserved ejection fraction. To date, the benefit of beta-blockers remains uncertain, and there is no current consensus on their effectiveness. This study sought to evaluate the efficacy of beta-blockers on mortality and rehospitalization among patientswith HFpEF.

Methods: A systematic review and meta-analysis ofrandomized or observational cohort studies examined the efficacy of beta-blocker therapy in comparison with placebo, control, or standard medical care in patients with HFpEF, defined as left ventricular ejection fraction ≥50 %. The main endpoints were mortality (i.e., all-cause and cardiovascular), rehospitalization (i.e., all-cause and for heart failure) and a composite of the two.

Results: Out of the 13,189 records initiallyidentified, 16 full-text records met the inclusion criteria and were analyzed recruiting a total of 27,188 patients. The mean age range was 62-84 years old,predominantly female, with HFpEF in which 63.4 % of patients received a beta-blocker and 36.6 % did not. The pooled analysis of included cohort studies, of variable follow-up durations, showed a significant reduction inall-cause mortality by 19 % whereas rehospitalization for heart failure or its composite with all-cause mortality were similar between the beta-blockerand control groups.

Conclusion : This meta-analysis showed that beta-blocker therapy has the potential to reduce all-causemortality in patients with HFpEF based on observational studies. Nevertheless, it did not affect rehospitalization for heart failure or its composite with all-cause mortality. Large scale randomized trials are needed to clarify thisuncertainty.

Disclaimer:

Lupin makes no representation or warranty of any kind, expressed or implied, regarding theaccuracy, adequacy, validity, reliability, availability, or completeness of any scientific information shared by the HCP on the STAR UPDATE podcast. Youshould not allow the contents of this to substitute for your own medical judgment, which you should exercise in evaluating the information on this website.

View Details

P2Y12 Inhibitor Monotherapy vs DualAntiplatelet Therapy After Deployment of a Drug-Eluting Stent: The SHARE Randomized Clinical Trial

JAMA Netw Open. 2024 Mar 4;7(3):e240877

Abstract

Importance: P2Y12 inhibitor monotherapy after dualantiplatelet therapy (DAPT; a P2Y12 inhibitor plus aspirin) for a brief duration has recently emerged as an attractive alternative for patients undergoing percutaneous coronary intervention with a drug-eluting stent.

Objective: To investigate whether P2Y12 inhibitormonotherapy after 3 months of DAPTwas noninferior to 12 months of DAPT following percutaneous coronary intervention with a drug-eluting stent.

Design, setting, and participants: The Short-TermDual Antiplatelet Therapy After Deployment of Bioabsorbable Polymer Everolimus-Eluting Stent (SHARE) open-label, noninferiority randomized clinicaltrial was conducted from December 15, 2017, toDecember 14, 2020. Final 1-year clinical follow-up was completed in January 2022. This study was a multicenter trial that was conducted at 20 hospitals inSouth Korea. Patients who underwent successful percutaneous coronary intervention with bioabsorbable polymer everolimus-eluting stents were enrolled.

Interventions: Patients were randomly assigned toreceive P2Y12 inhibitor monotherapy after 3 months of DAPT (n = 694) or 12 months of Dual Antiplatelet Therapy (n = 693).

Main outcomes and measures: The primary outcome was a net adverse clinical event, a composite of major bleeding and major adverse cardiac and cerebrovascular events (cardiac death, myocardial infarction, stentthrombosis, stroke, or ischemia-driven target lesion revascularization) between 3 and 12 months after the index percutaneous coronary intervention. The majorsecondary outcomes were major adverse cardiac and cerebrovascular events and major bleeding. The noninferiority margin was 3.0%.

Results: Of the total 1452 eligible patients, 65patients were excluded before the 3-month follow-up, and 1387 patients were assigned to P2Y12 inhibitor monotherapy or Dual Antiplatelet Therapy Between 3and 12 months of follow-up, the primary outcome occurred in 9 patients in the P2Y12 inhibitor monotherapy group and in 16 patients in the Dual Antiplatelet Therapy group .The major secondaryoutcomes major adverse cardiac and cerebrovascular events occurred in 8 patients in the P2Y12 inhibitormonotherapy group and in 12 patients inthe Dual Antiplatelet Therapy group . Major bleeding occurred in 1 patient in the P2Y12 inhibitor monotherapy group and in 5 patients in the Dual Antiplatelet Therapy group

Conclusions and relevance: In patients with coronaryartery disease undergoing percutaneous coronary intervention with the latest generation of drug-eluting stents, P2Y12 inhibitor monotherapy after 3-month DualAntiplatelet Therapy was not inferior to 12-month Dual Antiplatelet Therapy for net adverse clinical events. Considering the study population and lower-than-expected event rates, further research is required in other populations.

Disclaimer:

Lupin makes no representation or warranty of any kind, expressed or implied, regarding theaccuracy, adequacy, validity, reliability, availability, or completeness of any scientific information shared by the HCP on the STAR UPDATE podcast. You should not allow the contents of this to substitute for your own medicaljudgment, which you should exercise in evaluating the information on this website.

View Details

2024 ACC Expert Consensus Decision Pathway for Treatment of Heart Failure With Reduced Ejection Fraction: A Report of the American College of Cardiology Solution Set Oversight Committee.

J Am Coll Cardiol 2024;Mar 8:[Epub ahead of print].

In line with recent evidence and guidelines, therecommended core guideline-directed medical therapy (GDMT) for chronic heart failure (HF) includes an angiotensin II receptor/neprilysin inhibitor (ARNI), evidence-based beta-blocker, sodium-glucose cotransporter (SGLT) inhibitor, and mineralocorticoid antagonist (MRA). When feasible, early and rapid initiation of these therapies and titration to maximally tolerated doses within 3 months is recommended. While no specific order of initiation or titration of guideline-directed medical therapy is mandated, the following is some useful guidance a)Start with low doses of core therapies.

b) Delay beta-blocker initiation until HF is compensated.

c) ARNIs and SGLT inhibitors may reduce diuretic needs.

d) MRA and SGLT inhibitors may have minimal BP effects.

e) Mild declines in eGFR don't always require medicationcessation.

Difficulties with adherence to recommended HF therapies can be multifactorial. Effective strategies to improve adherence should be targeted to individual patient needs. Strategies include patient education,simplification of overall medication regimen, reduction of cost and access barriers, medication reminders, utilization of clinical pharmacist, and cognitive behavioral therapies. In addition to managing cardiovascular (CV) comorbidities, attention should be paid to addressing non-CV comorbidities that impact HF outcomes such as diabetes, chronic kidney disease, sleep-disorderedbreathing, iron deficiency, and viral infections (prevention with vaccination).

Disclaimer:

View Details

A novel score to predict in-hospital mortality for patients with acute coronary syndrome and out-of-hospital cardiacarrest: the FACTOR study

Clin Res Cardiol . 2024 Feb 8. doi: 10.1007/s00392-023-02367-1.

Abstract

Introduction: Acute coronary syndromes (ACS) represent a substantial global healthcare challenge. In its most severe form,it can lead to out-of-hospital cardiac arrest (OHCA). Despite medical advancements, survival rates in OHCA patients remain low. Further, the prediction of outcomes in these patients poses a challenge to all health care providers involved. This study aims at developing a score with variablesavailable on admission to assess in-hospital mortality of patients with OHCA undergoing coronary angiography.

Method: All patients with OHCA due to ACS admitted toa tertiary care center were included. A multivariate logistic regression analysis was conducted to explore the association between clinical variables and in-hospital all-cause mortality. A scoring system incorporating variables available uponadmission to assess individual patients' risk of in-hospital mortality was developed (FACTOR score). The score was then validated.

Results: A total of 291 patients were included in thestudy, with a median age of 65 [56-73] years, including 47 women (16.2%). The in-hospital mortality rate was 41.2%. A prognostic model was developed in the derivation cohort (n = 138) and included the following variables: age, downtime,first detected rhythm, and administration of epinephrine. The area under the curve for the FACTOR score was 0.823 (95% CI 0.737-0.894) in the derivation cohort and 0.828 (0.760-0.891) in the validation cohort (n = 153).

Conclusion: The FACTOR score demonstrated a reliableprognostic tool for health care providers in assessing in-hospital mortality of OHCA patients. Early acknowledgement of a poor prognosis may help in patient management and allocation of resources.

Disclaimer:

View Details

Ticagrelor versus Clopidogrel in Endovascular therapy for Cerebral Aneurysms: A Systematic Review andMeta-analysis

World Neurosurg . 2024 Feb 9:S1878-8750(24)00210-9

Abstract

Background: Antiplatelet therapy is pivotal inendovascular treatment for intracranial aneurysms. However, there is a lack of studies comparing ticagrelor to clopidogrel in patients with aneurysms undergoing endovascular therapy. Additionally, the existing literature lacks adequate sample size, significant subgrouping, and follow-up, making our studyimportant to cover these gaps.

Methods: We searched five databases to collect allrelevant studies. Categorical outcomes were pooled as relative risk (R.R.) with a 95% confidence interval (CI). In the single-arm meta-analysis, outcomes were pooled as proportions and their corresponding 95% CI.

Results: This comprehensive analysis of 18 studiesinvolving 2,427 patients. For thromboembolic events, the pooled (R.R.) did not show significant differences, whether considering overall events. A similar pattern was observed for thromboembolic events stratified by aneurysmal rupturestatus, with no significant differences in overall events. Hemorrhagic events did not also exhibit significant differences in previously mentionedstratifications. Furthermore, there were no substantial differences in death and mRS (0-2) on discharge between Ticagrelor and Clopidogrel. Single-arm meta-analyses for Ticagrelor demonstrated low rates of thromboembolic events,hemorrhage, death, and favorable mRS scores, with associated confidence intervals. Main line of endovascular treatment did not significantly affect either thromboembolic or hemorrhagic outcomes with Ticagrelor and Clopidogrel.

Conclusion: We found no significant differences inkey outcomes like thromboembolic events, hemorrhagic events, mortality rates, and favorable mRS (0-2) upon discharge in the studied patients between Ticagrelor and Clopidogrel. Moreover, the single-arm meta-analysis for Ticagrelor revealed low rates of thromboembolic events, hemorrhage, mortality,and high rates of favorable mRS scores.

Disclaimer:

View Details

Secondary Prevention Therapies in Real-World Patients with Myocardial Infarction: Eligibility Based on RandomizedTrials Supporting European and American Guideline

Am J Med . 2024 Feb;137(2):137-146.e10. doi:10.1016/j.amjmed.2023.09.021

Abstract

Objective: We aimed to evaluate the applicability ofthe eligibility criteria of randomized controlled trials (RCTs) cited in guideline recommendations in a real-world cohort of patients receiving secondary prevention after acute myocardial infarction from the EPICOR registries.

Methods: Recommendations provided by American andEuropean guidelines for acute myocardial infarction were classified into general (applying to all patients) and specific (applying to patients with left ventricular dysfunction or heart failure). Randomized controlled trials cited in these recommendations were selected, and their entry criteria were applied to our international cohort of 18,117 patients.

Results: There were 91.5% patients eligible for betablockers (84.6% for general, and 5.9% for specific recommendations), 97.7% eligible for renin-angiotensin system inhibitor (angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers [ACEI/ARB]) recommendations(69.9% for general, 27.9% for specific) and 4.1% eligible for mineralocorticoid receptor antagonists (only specific recommendations). The percentages of patients with eligibility criteria who were discharged with a prescription ofthe recommended therapies were 80%-85% for beta blockers, 70%-75% for ACEI/ARB, and 29% for mineralocorticoid receptor antagonists. There were large regional variations in the percentage of eligible patients and in those receiving themedications (eg, 95% in Northern Europe and 57% in Southeast Asia for beta blockers).

Conclusion: Most real-world acute myocardial infarction patients are eligible for secondary prevention therapy in bothgeneral and specific guideline recommendations, and the percentage of those on beta blockers and ACEI/ARB at hospital discharge is high. There are large regional variations in the proportion of patients receiving recommended therapies. Local targeted interventions are needed for quality improvement.

Disclaimer:

View Details

Factors Associated With Myocardial Infarction in a Rural Population With Peripheral Arterial Diseases

Angiology. 2024 Feb 6:33197241232608. doi:10.1177/00033197241232608.

Abstract

Peripheral arterial disease (PAD) studies in ruralpopulations are limited. The incidence of myocardial infarction (MI) is higher in patients with PAD. This study examined the association between sociodemographic and clinical risk factors and MI in patients with PAD in Central Appalachia, comprising of 230 countries across six states in the United States. Data from electronic medical records of 13,455 patients with PAD were extracted from a large health system in CentralAppalachia. Bivariate and logistic regression analyses were conducted. The final sample consisted of 5574 patients with PAD, of whom 24.85% were also diagnosed with MI. The mean age was 71 ± 11.23 years, and the majority were male (56.40%). After adjusting for confounders, patients with hypertension hadthree times higher odds of MI (adjusted Odds Ratio [aOR] = 3.21; 95% CI: 2.50-4.14) compared with those without hypertension. The likelihood of MI increased by 51% among patients with diabetes (aOR = 1.51; 95% CI: 1.33-1.71),34% among ever-smokers (aOR = 1.34; 95% CI: 1.18-1.52), and 45% in males (aOR = 1.45; 95% CI: 1.27-1.65). Hypertension, diabetes, smoking, and male sex were identified as significant risk factors for MI. Screening and effective management of these risk factors in rural areas could potentially prevent MIincidence among patients with PAD.

Disclaimer:

View Details

One year clinical outcome of dual anti-platelet therapy with the Novel Ticagrelor plus Aspirin versus Clopidogrelplus Aspirin for Endovascular Intervention of patients with Intracranial Aneurysm: A meta-analysis

J Stroke Cerebrovasc Dis. 2024 Jan;33(1):107491.

Abstract

Background: The use of stents to treat un-rupturedintracranial aneurysms was first approved in the year 2002 in the United States as a Humanitarian Device Exemption. Antiplatelet therapy is mandatory following stent placement. Dual antiplatelet therapy (DAPT) with aspirin and clopidogrelhas been the first line agents for the prevention of thromboembolic events following neuro-endovascular procedures. However, clopidogrel hypo-responsiveness has often been observed. In this analysis, we aimed tosystematically compare one year clinical outcome of DAPT with the Novel Ticagrelor plus Aspirin versus Clopidogrel plus Aspirin for Endovascular Intervention of patients with Intracranial Aneurysm.

Methods: Online electronic databases were searchedfrom June 2023 till July 2023 for relevant studies which compared DAPT with ticagrelor or clopidogrel for endovascular intervention in patients with intracranial aneurysm. The endpoints which were analyzed were classified into thromboembolic and hemorrhagic events. A fixed and a random effect statistical model were used during data analysis respectively. Risk ratio (RR) with 95 % confidence interval (CI) was used to represent the data following analysis.

Results: Five studies with a total number of 893participants were included in this analysis. Three hundred and fifty eight (358) participants were assigned to the ticagrelor group whereas 535 participants were assigned to clopidogrel group. Participants' enrollment period ranged from the year 2009 to 2019. Our results showed that during a meanfollow-up time period of one year, DAPT with ticagrelor was associated with significantly lower thromboembolic events with RR: 0.33, 95 % CI: 0.16 - 0.68; P = 0.003. In addition, at one year, DAPT with ticagrelor was not associatedwith any increase in hemorrhagic events (RR: 0.66, 95 % CI: 0.29 - 1.50; P = 0.32) when compared to DAPT with clopidogrel.

Conclusion: At one year, DAPT with ticagrelor wasassociated with significantly lower thromboembolic events without any increase in hemorrhagic events when compared to clopidogrel associated DAPT for endovascular intervention of patients with intracranial aneurysm. However, eventhough ticagrelor-associated DAPT use appeared to be more effective and safe, this hypothesis should only be confirmed in larger upcoming trials.

Disclaimer:

Lupin makes no representation or warranty of any kind, expressed or implied, regarding the accuracy,adequacy, validity, reliability, availability, or completeness of any scientific information shared by the HCP on the STAR UPDATE podcast. You should not allow the contents of this to substitute for your own medical judgment, which you should exercise in evaluating the information on this website.

View Details

Beta-blocker therapy in heart failure with preserved ejection fraction (B-HFpEF): a systematic review and meta-analysis

Curr Probl Cardiol . 2024 Jan 4:102376. doi:10.1016/j.cpcardiol.2024.102376.

Abstract

Introduction: While beta-blockers are considered thecornerstone of treatment for heart failure with reduced ejection fraction, the same may not apply to patients with heart failure with preserved ejection fraction (HFpEF). To date, the benefit of beta-blockers remains uncertain, and there is no current consensus on their effectiveness. This study sought toevaluate the efficacy of beta-blockers on mortality and rehospitalization among patients with HFpEF.

Methods: A systematic review and meta-analysis ofrandomized or observational cohort studies examined the efficacy of beta-blocker therapy in comparison with placebo, control, or standard medical care in patients with HFpEF, defined as left ventricular ejection fraction ≥50%. The main endpoints were mortality (i.e., all-cause and cardiovascular),rehospitalization (i.e., all-cause and for heart failure) and a composite of the two.

Results: Out of the 13,189 records initially identified, 16 full-text records met the inclusion criteria and were analyzedrecruiting a total of 27,188 patients. The mean age range was 62 - 84 years old, predominantly female, with HFpEF in which 63.4% patients received a beta-blocker and 36.6% did not. The pooled analysis of included cohort studies, of variable follow-up durations, showed a significant reduction in all-causemortality by 19% (odds ratio (OR) 0.81; 95% confidence interval (CI): 0.65-0.99, p=0.044) whereas rehospitalization for heart failure (OR 1.13; 95% CI: 0.91-1.41, p=0.27) or its composite with all-cause mortality (OR 1.01; 95% CI: 0.78-1.32, p=0.92) were similar between the beta-blocker and control groups.

Conclusion: This meta-analysis showed that beta-blocker has the potential to reduce all-cause mortality in patients withHFpEF based on observational studies. Nevertheless, rehospitalization for heart failure or its composite with all-cause mortality. Large scale randomized trials are needed to clarify this uncertainty.

Disclaimer:

Lupin makes no representation or warranty of any kind, expressed or implied, regarding the accuracy, adequacy, validity, reliability, availability, or completeness of any scientific information shared by the HCP on the STAR UPDATE podcast. You should not allow the contents of this to substitute foryour own medical judgment, which you should exercise in evaluating the information on this website

View Details

The Prognostic impact of treatmentsevolution in STEMI

Int J Cardiol. 2024 Jan 1:394:131352. doi:10.1016/j.ijcard.2023.131352

Abstract

Objective: To evaluate in a real-world primary percutaneous coronary intervention (pPCI) registry the impact of the evolution of evidence-based treatments on prognosis.

Methods: STEMI patients undergoing pPCI at theUniversity Hospital of Trieste, Italy, were enrolled. The first cohort (old treatments cohort) included STEMI patients treated between January-2007 and December-2012, and the second cohort (new treatments cohort), between January-2013 andDecember-2020. Inverse Probability of Treatment Weighting (IPTW) Cox regression models as well as multivariable Cox regression models were performed to assess the risk of a composite primary endpoint (PE) of all cause death, reinfarction and re-PCI at 5 years.

Results: A total of 2425 STEMI patients were enrolled. At multivariable Cox regression, the new-treatments cohort had lower risk of PE and mortality. Weighted (IPTW) Cox proportional hazard models confirmed the lower risk of the new treatments cohort for PE (HR 0.72; 95% CI 0.56-0.91, p = 0.007) and 5-year mortality (HR 0.70, 95%CI 0.54-0.91, p =0.009). When considering both clinical and procedural variables, complete revascularization (HR 0.46, 95%CI 0.27-0.80, p = 0.006) and the administration of prasugrel or ticagrelor (HR 0.72, 95%CI 0.52-0.99, p = 0.013) wereindependent predictors of PE as well as of 5-year mortality. Patients receiving prasugrel or ticagrelor or drug eluting stent were at lower risk of 1-year stent thrombosis (HR 0.50, 95%CI 0.28-0.90, p = 0.021).

Conclusions: In a real-word STEMI population theprognosis of patients has improved in the last decades, and this was associated to the use of new antithrombotic treatments and to the implementation of complete revascularization.

Disclaimer:

Lupin makes no representation or warranty of any kind, expressed or implied, regarding the accuracy,adequacy, validity, reliability, availability, or completeness of any scientific information shared by the HCP on the STAR UPDATE podcast. You should not allow the contents of this to substitute for your own medical judgment, which you should exercise in evaluating the information on this website.

View Details

Predictive value of the thrombotic risk criteria proposed in the 2023 ESC guidelines for the management of ACS: insights from a large PCI registry

Eur Heart J Cardiovasc Pharmacother. 2024 Jan5;10(1):11-19. doi: 10.1093/ehjcvp/pvad069

Abstract

Aim: To assess the value of the thrombotic risk criteria proposed in the 2023 guidelines of the European Society of Cardiology (ESC) for the management of acute coronary syndrome (ACS) to predict the ischaemic risk after percutaneous coronary intervention (PCI).

Methods and results: Consecutive patients with acuteor chronic coronary syndrome undergoing PCI at a large tertiary-care center from 2014 to 2019 were included. Patients were stratified into low, moderate, or high thrombotic risk based on the ESC criteria. The primary endpoint wasmajor adverse cardiovascular events (MACEs) at 1 year, a composite of all-cause death, myocardial infarction (MI), and stroke. Secondary endpoints included major bleeding. Among 11 787 patients, 2641 (22.4%) were at low-risk, 5286 (44.8%) at moderate risk, and 3860 (32.7%) at high-risk. There was anincremental risk of MACE at 1 year in patients at moderate (hazard ratios (HR) 2.53, 95% confidence interval (CI) 1.78-3.58) and high-risk (HR 3.39, 95% CI 2.39-4.80) as compared to those at low-risk, due to higher rates of all-cause death and MI. Major bleeding rates were increased in high-risk patients (HR1.59, 95% CI 1.25-2.02), but similar between the moderate and low-risk group.The Harrell's C-index for MACE was 0.60.

Conclusion: The thrombotic risk criteria of the 2023ESC guidelines for ACS enable to stratify patients undergoing PCI in categories with an incremental 1 year risk of MACE; however, their overall predictive ability for MACE is modest. Future studies should confirm the value of thesecriteria to identify patients benefiting from an extended treatment with a second antithrombotic agent.

Disclaimer:

Lupin makes no representation or warranty of any kind, expressed or implied, regarding the accuracy,adequacy, validity, reliability, availability, or completeness of any scientific information shared by the HCP on the STAR UPDATE podcast. You should not allow the contents of this to substitute for your own medical judgment, which you should exercise in evaluating the information on thiswebsite.

View Details

Prognostic significance of medical therapy in patients with heart failure with reduced ejection fraction

ESC Heart Fail. 2023 Dec;10(6):3677-3689. doi: 10.1002/ehf2.14559

Abstract

Aims: The use of guideline-directed medical therapy(GDMT) among patients with heart failure (HF) with reduced ejection fraction (HFrEF) remains suboptimal. The SMYRNA study aims to identify the clinical factors for the non-use of GDMT and to determine the prognostic significance ofGDMT in patients with HFrEF in a real-life setting.

Methods and results: The SMYRNA study is aprospective, multicentre, and observational study that included outpatients with HFrEF. Patients were divided into three groups according to the status of GDMT at the time of enrolment: (i) patients receiving all classes of HF medications including renin-angiotensin system (RAS) inhibitors, beta-blockers,and mineralocorticoid receptor antagonists (MRAs); (ii) patients receiving any two classes of HF medications (RAS inhibitors and beta-blockers, or RAS inhibitors and MRAs, or beta-blockers and MRAs); and (iii) either patients receiving class of HF medications (only one therapy) or patients not receivingany class of HF medications. The primary outcome was a composite of hospitalization for HF or cardiovascular death. The study population consisted of 1062 patients with HFrEF, predominantly men (69.1%), with a median age of 68(range: 20-96) years. RAS inhibitors, beta-blockers, and MRAs were prescribed in 76.0%, 89.4%, and 55.1% of the patients, respectively. The proportions of patients receiving target doses of guideline-directed medications were 24.4% for RAS inhibitors, 11.0% for beta-blockers, and 11.1% for MRAs. Overall, 491 patients (46.2%) were treated with triple therapy, 353 patients (33.2%) were treated with any two classes of HF medications, and 218 patients (20.6%) werereceiving only one class of HF medication or not receiving any HF medication. Patient-related factors comprising older age, New York Heart Association functional class, rural living, presence of hypertension, and history of myocardial infarction were independently associated with the use or non-use ofGDMT. During the median 24-month period, the primary composite endpoint occurred in 362 patients (34.1%), and 177 of 1062 (16.7%) patients died. Patients treated with two or three classes of HF medications had a decreased risk of hospitalization for HF or cardiovascular death compared with those patients receiving ≤1 class of HF medication [hazard ratio (HR): 0.65; 95% confidence interval (CI): 0.49-0.85; P = 0.002, and HR: 0.61; 95% CI: 0.47-0.79; P < 0.001, respectively].

Conclusions: The real-life SMYRNA study provided comprehensive data about the clinical factors associated with the non-use of GDMT and showed that suboptimal GDMT is associated with an increased risk of hospitalization for HF or cardiovascular death in patients with HFrEF.

Disclaimer:

Lupin makes no representation or warranty of any kind, expressed or implied, regarding the accuracy, adequacy, validity, reliability, availability, or completeness of any scientific information shared by the HCP on the STAR UPDATE podcast. You should not allow the contents of this to substitute for your own medical judgment, which you should exercise in evaluating the information on this website.

View Details

Effect of beta-blockers and exercise restriction on the prevention of sudden cardiac death in pediatric hypertrophiccardiomyopathy

JCardiol. 2023 Dec 2:S0914-5087(23)00288-5. doi: 10.1016/j.jjcc.2023.11.009.

Abstract

Background: Risk assessment tools and effective prevention strategies for sudden cardiac death (SCD) in pediatric patients with hypertrophic cardiomyopathy (HCM) have not been established. This study aimed to evaluate the efficacy of beta-blockers and exercise restriction for SCD prevention in this population.

Methods: We retrospectively reviewed the medicalrecords of patients aged <18 years who were diagnosed with HCM at our center between January 1996 and December 2021. SCD and aborted SCD were defined as SCD equivalents. We divided patients based on whether they were prescribedbeta-blockers or exercise restriction and compared the outcomes among the groups. The primary outcome was the overall survival (OS), and the secondary outcome was the cumulative SCD equivalent rate. Outcomes were analyzed usingKaplan-Meier curves and Cox proportional hazard analysis. We also compared patients according to the occurrence of SCD equivalents to identify SCD risk predictors.

Results: Among the 43 included patients [mean age,7.7 (1.6-12.1) years; 23 male individuals], SCD equivalents occurred in 13 patients over 11.2 (4.5-15.6) years of follow-up, among whom 12 were resuscitated and 1 died. The OS rate was significantly higher in the beta-blocker and exercise restriction groups than in the non-beta-blocker and non-exercise restriction groups (81.3 % vs. 19.1 %, p < 0.01 and 57.4 % vs.12.7 %, p < 0.01, respectively). Among the 13 patients with SCD equivalents, 5 had 9 recurrent SCD equivalents. A significant difference was observed between the SCD equivalent and non-SCD equivalent groups in the history of suspected arrhythmogenic syncope (p < 0.01) in the univariable but not inthe multivariable analysis.

Conclusions: Beta-blockers and exercise restrictionmay decrease the risk of SCD in pediatric patients with HCM and should be considered for SCD prevention in this population, particularly because predicting SCD in these patients remains challenging.

Disclaimer:

Lupin makes no representation or warranty of any kind, expressed or implied, regarding the accuracy, adequacy, validity, reliability, availability, or completeness of any scientific information shared by the HCP on the STAR UPDATE podcast. You should not allow the contents of this to substitute for your own medical judgment, which you should exercise in evaluating the information on this website.

View Details

Emergent use of ticagrelor during endovascular reperfusion in large arterial occlusions

J Stroke Cerebrovasc Dis . 2023 Dec;32(12):107351. doi:10.1016/j.jstrokecerebrovasdis.2023

Abstract

Objective: Given many emerging indications for endovascular interventions in ischemic strokes, a safe andeffective adjuvant antiplatelet regimen for acute revascularization has become a subject of interest. Ticagrelor is a direct oral P2Y12 inhibitor that may achieve rapid platelet suppression than standard oral therapies. We report ourexperience of Ticagrelor use in revascularization of acute large arterial steno-occlusive disease, describing procedural post procedure thrombotic events, major hemorrhages, and other clinical outcomes.

Methods: This was a single-center retrospective case series of large steno-occlusive disease requiring endovascular reperfusion with emergent adjuvant Ticagrelor, defined as 30 min of the procedure from skin puncture to closure of the arteriotomy. Major outcomes investigated were thromboembolism in the target artery, and symptomatic intracranial or extracranial major hemorrhages. Additional analyses were performed with respect to timing of the administration and use of rescue GPIIb/IIIa inhibitors if any.

Results: 73 consecutive patients were identified, presenting with severe ischemic stroke (median NIHSS 16) of large artery origin. 67% required stent placement (45% cervical carotid, 22%intracranial artery), 9.5% angioplasty and 23% mechanical thrombectomy only. Two experienced symptomatic in-stent occlusion, and 7 experienced major hemorrhages (9.5%) including 3 fatal symptomatic intracranial hemorrhages(4.1%). Among 19 subjects (26%) who received pretreatment with Ticagrelor, there were fewer GPIIb/IIIa administration, angioplasty and stenting, without yielding benefit in functional outcome or mortality. GPIIb/IIIa was administered as rescue therapy in 45 subjects (62%), which was found associatedwith increased bleeding compared to patients receiving Ticagrelor only, in whom no bleeding complications were recorded (16% vs. 0%; p = 0.03).

Conclusion: We report our findings on Ticagrelor as an adjuvant antiplatelet therapy in ischemic stroke of large arterial origin requiring emergent revascularization. Effectiveness, safety,need for additional rescue treatment, and comparison to other commonly used oral antiplatelets should be investigated in future prospective studies.

Disclaimer:

Lupin makes no representation or warranty of any kind, expressed or implied, regarding the accuracy, adequacy, validity, reliability, availability, or completeness of any scientific information shared by the HCP on the STAR UPDATE podcast. You should not allow the contents of this to substitute for your own medical judgment, which you should exercise in evaluating the information on this website.

View Details

De-escalation of Antiplatelet Therapy After Percutaneous Coronary Intervention in East Asian Patients With AcuteCoronary Syndrome

Clin Ther. 2023 Dec 8:S0149-2918(23)00305-3.doi: 10.1016/j.clinthera.2023.08.004

Abstract

Purpose: East Asian individuals have a lower risk of thromboembolic events while potentially carrying a higher riskof bleeding events compared with non-Asian individuals. The aim of the present analysis was to investigate the effectiveness and safety of the de-escalation of antiplatelet therapy compared with standard dual antiplatelet therapy (DAPT)in East Asian patients undergoing percutaneous coronary intervention (PCI).

Methods: Randomized controlled trials comparing de-escalation with DAPT in patients with acute coronarysyndrome (ACS) were retrieved from electronic databases from their inception until March 2022. Outcomes included major adverse cardiovascular events (MACE), ischemic events, major bleeding, minor bleeding, and any bleeding. Subgroupanalyses based on treatment strategy were conducted. Statistical analysis was performed by using Review Manager version 5.4.

Findings: Eight randomized controlled trials from 539 potentially relevant publications with a total of 15,744 East Asian patients were included. Pooled data from these studies founda significantly lower MACE (0.82; 95% CI, 0.69-0.98) and major bleeding event (0.62; 95% CI, 0.46-0.82) in de-escalation than standard-DAPT without heterogeneity. Subgroup analysis was divided into DAPT followed by P2Y12 inhibitor monotherapy and a reducing dose of P2Y12 inhibitors. DAPT followed byP2Y12 inhibitor monotherapy had a 48% lower incidence of major bleeding events than standard DAPT (0.52; 95% CI, 0.27-1.00); there was no significant difference in major bleeding (0.99; 95% CI, 0.55-1.76) between the reducingdose of P2Y12 inhibitors and standard DAPT.

Implications: De-escalation is a promising and potentially optimal antiplatelet therapy for patients from EastAsia with PCI. DAPT followed by P2Y12 inhibitor monotherapy might be a safer and equally effective approach compared with standard DAPT in East Asian patients with PCI.

Disclaimer:

Lupin makes no representation or warranty of any kind, expressed or implied, regarding the accuracy, adequacy, validity, reliability, availability, or completeness of any scientific information shared by the HCP on the STAR UPDATE podcast. You should not allow the contents of this to substitute for your own medical judgment, which you should exercise in evaluating the information on this website.

View Details

A new meta-analysis of the two trials showed that "oral anticoagulation with edoxaban or apixaban reduces the risk of ischemic stroke by approximately one-third and increasesmajor bleeding by roughly double.

In absolute numbers, there were three fewer ischemic strokes per 1000 patient years with anticoagulation in the two trials combined, at the cost of seven more major bleeds.

In patients with pacemakers or implantable loop recorders with continuous monitoring, subclinical AF is detected in about one third of patients.

The totality of risk factors in each patient — their bleeding risk, stroke risk, how much AF they have, and make a decision as to whether to give anticoagulation or not."

Results:

Both trials showed the stroke rate is low in these patients — about 1% per year — and that anticoagulation can reduce it a bit further at the expense of increasing major bleeding. The AF episodes picked up on these devices constitute a sumcient stroke risk to warrant anticoagulation, given the bleeding risk."

Disclaimer: Lupin makes no representation or warranty of any kind, expressed or implied, regarding the accuracy, adequacy, validity, reliability, availability, or completeness of anyscientific information shared by the HCP on the STAR UPDATE podcast. You should not allow the contents of this to substitute for your own medical judgment, which you should exercise in evaluating the information on this website.

View Details

People who followed a low-salt diet for just a week experienced a reduction in systolic blood pressure of about 6 mm Hg, in a new study.

Raised blood pressure contributes to 1 out of every 8 deaths worldwide. "If people want to lower their blood pressure, attention to dietary sodium is one part of that. If individuals can stick with a low sodium diet, they may be able to stop taking one of their antihypertensive medications, and those who are normotensive will be less likely to develop hypertension."

The CARDIA-SSBP trial involved 213 individuals aged 50-75 years, including those with and those without hypertension, and showed that the decline in blood pressure brought about by a low-salt diet was independent of hypertension status and antihypertensive medication use. It was also generally consistent across subgroups and did not result in excess adverse events.

For the study, participants had their blood pressure measured by 24-hour ambulatory monitoring while on their usual diets. They were then randomly assigned to either a high-sodium diet or a low-sodium diet for 1 week. Participants then crossed over to the opposite diet for 1 week, with blood pressure measured over a 24-hour periodon the last day of each diet.

The diet in this study brought about a large reduction in dietary sodium, but any reduction in dietary sodium is likely to be beneﬁcial.

View Details

Aspirin may not be necessary or beneﬁcial in patients with advanced heart failure who get a left ventricular assist device (LVAD), new randomized results suggest.

"We've always thought that somehow aspirin prevents stroke and prevents clotting and that it's anti-inﬂammatory, and what we found in ARIES was the exact opposite," saidMandeep Mehra, MD, of Brigham and Women's HospitalHeart and Vascular Center and Harvard Medical School in Boston, Massachusetts, who reported results of the ARIES-HM3 trial of the HeartMate 3 LVAD, a device that uses a fully magnetically levitated rotor to maintain blood ﬂow.

ARIES-HM3 randomly assigned 589 patients who received the HeartMate 3 device to vitamin K therapy with aspirin or to placebo.

Result:

The bleeding rates would decrease by 34% and that gastrointestinal (GI) bleeding in particular would decrease by 40%. We didn't expect that it would nearly halve the days spentin the hospital, and we didn't expect that the cost of care woulddecrease by 40%."

The researchers found that 74% of patients in the placebo group met the primary endpoint of being alive and not having any hemocompatibility events at 12 months vs 68% of the aspirin patients. The rate of nonsurgical bleeding events was 30% in the placebo group vs 42.4% in the aspirin patients. The rates of GI bleeding were 13% and 21.6% in the respective groups.

The placebo group spent 47% fewer days in the hospital for bleeding, with hospitalization costs 41% lower than the aspiringroup.

Disclaimer: Lupin makes no representation or warranty of any kind, expressed or implied, regarding the accuracy, adequacy, validity, reliability, availability, or completeness of any scientific information shared by the HCP on the STAR UPDATE podcast. You should not allow the contents of this to substitute for your own medical judgment, which you should exercise in evaluating the information on this website.

View Details

In patients with myocardial infarction (MI) and anemia, a "liberal" red blood cell (RBC)transfusion strategy signiﬁcantly reduce the risk of recurrent MI or death within 30 days compared with a "restrictive" transfusion strategy, in the 3500-patient MINT trial.

A liberal transfusion strategy may be the most prudent approach to transfusion in anemic patients with MI

We cannot claim that a liberal transfusion strategy is deﬁnitively superior based on our

primary outcome," he said, but "the 95% conﬁdence interval is consistent with treatment effects corresponding to no difference between the two transfusion strategies and to a clinically relevant beneﬁt with the liberal strategy."

The number needed to treat was 40 to see a beneﬁt in the combined outcome of death or recurrent MI at 30 days, The P-value for this was 0.07, "right on the edge" of statistical signiﬁcance.

"In contrast to other trials in other settings," such as anemia and cardiac surgery, "theresults suggest that a liberal transfusion strategy has the potential for clinical beneﬁt with an acceptable risk of harm."

"While not statistically signiﬁcant, the results consistently favored a liberal transfusion strategy,"

Notably, cardiovascular death, which was not a speciﬁed outcome, was signiﬁcantly lower in the group who received a liberal transfusion strategy.

Disclaimer: Lupin makes no representation or warranty of any kind, expressed or implied, regarding the accuracy, adequacy, validity, reliability, availability, or completeness of any scientific information shared by the HCP on the STAR UPDATE podcast. You should not allow the contents of this to substitute for your own medical judgment, which you should exercise in evaluating the information on this website.

View Details

Comparison of Ticagrelor Monotherapy and Ticagrelor Plus Aspirin Among Patients With Acute Coronary SyndromeCombined With High-Risk of Gastrointestinal Bleeding After PercutaneousCoronary Intervention: A Retrospective Cohort Study

J Cardiovasc Pharmacol. 2023 Oct 1;82(4):327-332. doi:10.1097/FJC.0000000000001461

Abstract

To date, no studies have specifically examined the efficacy of P2Y12 inhibitor monotherapy in patients with acute coronary syndrome (ACS) exhibiting a high risk of gastrointestinal (GI) bleeding following percutaneous coronary intervention(PCI). This was a retrospective cohort study of ACS exhibiting a high GI bleeding risk after PCI admitted to the Affiliated Hospital of the Jiangnan University from August 2016to December 2019. Of the 308 enrolled patients, 269 were found eligible and were assigned to the ticagrelor monotherapy (TIC) arm (n = 128) and to ticagrelor plus aspirin (TIC + ASP) arm (n = 141) treatment for a 1-year period. The primary study outcome was a composite end point, including bleedingacademic research consortium (BARC) type 2, 3, or 5 bleeding and adverse cardiac or cerebrovascular events; 8 (6.3%) in the TIC group and 14 (9.9%) in the combination treatment group reached the primary ischemic end point within 1 year with no significant difference between these groups. BARC type 2, 3, and 5 bleeding events affected significantly more patients in the combination group relative to the TIC group (38 [27.0%] vs. 11 [8.6%], P < 0.001). As the follow-up interval was prolonged, the cumulative BARC type 2, 3, and 5 bleeding incidence in the TIC group remained significantly below than that in the combination treatment group ( P < 0.05).

These results indicate that TIC is associated with a lower risk of clinically relevant bleeding events among ACS with a highrisk of GI bleeding after PCI relative to combination TIC + ASP treatment, although ischemic outcomes in these 2 groups were similar.

Disclaimer:

Lupin makes no representation or warranty of any kind, expressed or implied, regarding the accuracy, adequacy, validity, reliability, availability, or completeness of any scientific information shared by the HCP on the STAR UPDATE podcast. You should not allow the contents of this to substitute for your own medical judgment, which you should exercise in evaluating the information on this website.

View Details

Sex and Age Differences of Major Cardiovascular Events in Patients After Percutaneous Coronary Intervention

J Chin Med Assoc . 2023 Oct 10.

doi: 10.1097/JCMA.0000000000001011

Abstract

Background: Women usually have higher risk after receiving percutaneous coronary interventions (PCIs) than men withcoronary artery disease (CAD). The aim of this study was to investigate the association of sex differences with future outcomes in CAD patients undergoing PCI, to assess the role of age, and to extend observed endpoints to stroke andcongestive heart failure.

Methods: 6,647 patients with CAD who receivedsuccessful PCIs. The associations between clinic outcomes and sex were analyzed. The primary outcome was major cardiovascular events (MACE), includingcardiac death, nonfatal myocardial infraction, and nonfatal stroke. The secondary outcome was MACE and hospitalization for heart failure (total CVevents).

Results: During a mean of 52.7 months of follow-up, 4833 men and 1614 women received PCI. Univariate and multivariateanalyses showed that women were independently associated with an increased risk of cardiac death (HR: 1.78; 95% CI: 1.32-2.41), hospitalization for heart failure (HR: 1.53, 95% CI: 1.23-1.89), MACE (HR: 1.34; 95% CI: 1.10-1.63), and total CV events (HR: 1.39; 95% CI: 1.20-1.62). In the subgroup analysis, womenunder 60 years of age had higher cardiovascular risks than men of the same age category.

Conclusion: Women with CAD after successful PCIhad poorer cardiovascular outcomes than men. Additionally, younger women (age <60 years) were especially associated with a higher risk of developing future adverse cardiovascular outcomes.

Disclaimer:

Lupin makes no representation or warranty of any kind, expressed or implied, regarding the accuracy, adequacy, validity, reliability, availability, or completeness of any scientific information shared by the HCP on the STAR UPDATE podcast. You should not allow the contents of this to substitute for your own medical judgment, which you should exercise in evaluating the information on this website.

View Details

Effectiveness and Safety of P2Y12 Inhibitor Pretreatment for Primary PCI in STEMI: Systematic Review and Meta-analysis

J Cardiovasc Pharmacol. 2023 Oct 1;82(4):298-307. doi:10.1097/FJC.0000000000001460

Abstract

Dual antiplatelet therapy with aspirin and P2Y12 inhibitors in patients with ST-segment elevation myocardial infarction (STEMI) has been shown to be associated with better outcomes. Yet, there is uncertainty regarding the optimal timing for its initiation. We performed a systematic review and meta-analysis of evidence on pretreatment with P2Y12 inhibitors in combination with aspirin in patients with STEMI undergoingprimary percutaneous coronary intervention (PCI). We performed a systematic search of electronic databases PubMed, CENTRAL, and Scopus until April 2022.Studies were eligible if they compared P2Y12 inhibitor upstream administration with downstream use in patients with STEMI submitted to PCI. Studies with patients receiving fibrinolysis or medical therapy only were excluded. Outcomeswere assessed at the shortest follow-up available. Of 2491 articles, 3 RCT and 16 non-RCT studies were included, with a total of 79,300 patients (66.1% pretreated, 66.0% treated with clopidogrel). Pretreatment was associated with reduction in definite stent thrombosis (odds ratio [OR] 0.61 [0.38-0.98]),all-cause death (OR 0.77 [0.60-0.97]), and cardiogenic shock (OR 0.60 [0.48-0.75]). It was also associated with a lower incidence of thrombolysis in myocardial infarction flow <3 pre-PCI (OR 0.78 [0.67-0.92]). However, incidence of recurrent MI was not significantly reduced (OR 0.93 [0.57-1.52]). Regardingsafety, pretreatment was not associated with a higher risk of major bleeding events (OR 0.83 [0.75-0.92]).

Pretreatment with dual antiplatelet therapy, including a P2Y12 inhibitor, was associated with better pre-PCI coronaryperfusion, lower incidence of definite stent thrombosis, cardiogenic shock, and, possibly, all-cause mortality with no sign of potential harm encountered.

Disclaimer:

View Details

β1-blockers in the reduction of bleeding risk in patients prescribed with potent dual antiplatelet therapy after acute coronary syndrome or percutaneous coronary intervention

Hellenic J Cardiol. 2023 Oct 12:S1109-9666(23)00188-4. doi: 10.1016/j.hjc.2023.09.017

Abstract

Background: β1-blockers could improve clinicaloutcomes in patients with coronary artery disease by lowering the heart rate, blood pressure, and myocardial contractility. Moreover, recent studies have suggested that β1-blockers may also have the potential to reduce bleeding risk.

Objectives: This study aimed to evaluate theassociation between β1-blockers and bleeding risk in the patients prescribed with potent dual antiplatelet therapy (DAPT) after acute coronary syndrome (ACS) or percutaneous coronary intervention (PCI).

Methods: Patients with ACS or undergoing PCI treated by DAPT of ticagrelor and aspirin were consecutively recruited.Follow-up for all eligible patients was conducted for 1 year. Major bleeding outcomes were defined as events that were type ≥2 based on the Bleeding Academic Research Consortium (BARC) criteria.

Results: A total of 1,113 eligible ticagrelor-treated patients were recruited. During the 1-year follow-up interval, 142 (12.6%) patients experienced BARC ≥2 bleedings including 23patients (2.1%) suffering BARC ≥3 bleedings, with the most common site of bleeding located in the gastrointestinal tract. β1-blockers treatment was associated with a lower risk of BARC ≥2 bleedings (11.2% vs. 23.3%, adjusted HR: 0.42, 95% CI: 0.28-0.62, P < 0.01). Moreover, metoprolol (11.1% vs. 23.3%, adjusted HR: 0.56, 95% CI: 0.37-0.83, P < 0.01) and bisoprolol (11.3%vs. 23.3%, adjusted HR: 0.56, 95% CI: 0.33-0.96, P = 0.04) had similar effects on the reduction of bleeding risk.

Conclusion: β1-blockers might be beneficial for the reduction of bleeding risk in potent dual antiplatelet therapy patientswith ACS or undergoing PCI.

Disclaimer:

View Details

Heart failure pharmacological treatmentsand outcomes in heart failure with mildly reduced ejection fraction

Eur Heart J Cardiovasc Pharmacother. 2023 Sep 20;9(6):526-535.

Abstract

Background: Guideline recommendations for the treatment of heart failure with mildly reduced ejection fraction (HFmrEF) derive from small subgroups in post-hoc analyses of randomized trials.

Objectives: We investigated predictors of renin-angiotensin system inhibitors/angiotensin receptor neprilysin inhibitors (RASI/ARNI) and beta-blockers use, and the associations between these medications and mortality/morbidity in a large real-world cohort with HFmrEF.

Methods and results: Patients withHFmrEF (EF 40-49%) from the Swedish HF Registry were included. The associations between medications and cardiovascular (CV) mortality/HF hospitalization (HFH),and all-cause mortality were assessed through Cox regressions in a 1:1 propensity score-matched cohort. A positive control analysis was performed in patients with EF < 40%, while a negative control outcome analysis had cancer-related hospitalization as endpoint. Of 12 421 patients with HFmrEF, 84% received RASI/ARNI and 88% beta-blockers. Shared-independent predictors of RASI/ARNI and beta-blockers use were younger age, being an outpatient, follow-up in specialty care, and hypertension. In the matched cohorts, use ofboth RASI/ARNI and beta-blocker use was separately associated with lower risk of CV mortality/HFH [hazard ratio (HR) = 0.90, 95% confidence interval (CI): 0.83-0.98 and HR = 0.82, 95% CI: 0.74-0.90, respectively] and of all-cause mortality (HR = 0.75, 95% CI: 0.69-0.81 and HR = 0.79, 95% CI: 0.72-0.87,respectively). Results were consistent at the positive control analysis, and there were no associations between treatment use and the negative control outcome.

Conclusions: RASI/ARNI and beta-blockers were extensivelyused in this large real-world cohort with HFmrEF. Their use was safe since associated with lower mortality and morbidity. Our findings confirm the real-world evidence from previous post-hoc analyses of trials, and represent a further call for implementing guideline recommendations.

Disclaimer:

Lupin makes no representation or warranty of any kind,expressed or implied, regarding the accuracy, adequacy, validity, reliability, availability, or completeness of any scientific information shared by the HCP on the STAR UPDATE podcast. You should not allow the contents of this to substitute for your own medical judgment, which you should exercise inevaluating the information on this website.

View Details

Effect of ticagrelor and clopidogrel dual antiplatelet therapy on MPVLR, MAADP, and AA inhibition rate in acute coronarysyndrome patients after percutaneous coronary intervention

Medicine(Baltimore). 2023 Sep 15;102(37):e34974.

Abstract

Objective: To explore the effects of ticagrelor andclopidogrel dual antiplatelet therapy on the mean platelet volume-to-lymphocyte ratio (MPVLR), maximum amplitude of adenosine diphosphate-induced platelet-fibrin clots (MAADP), and arachidonic acid (AA) inhibition rates in patients with acute coronary syndrome (ACS) after percutaneous coronaryintervention (PCI).

Methods: A total of 120 patients with ACS undergoingelective PCI in our hospital between March 2020 and November 2021 were recruited. Patients were divided into 2 groups using the random number table method, with 60 patients in each group. The control group received clopidogrel+ aspirin dual antiplatelet therapy, while the study group received ticagrelor + aspirin dual antiplatelet therapy. MPVLR, MAADP, and AA inhibition rates were compared between the 2 groups. Platelet activation indices, platelet micro PNA-223, and platelet gelsolin levels were measured before and 4 weeks afterPCI. Changes in cardiac function indices, bleeding rates, and major adverse cardiovascular events (MACE) were compared between groups.

Results: The MAADP score of the study group was lowerthan that of the control group 3 days after surgery (P < .05). Compared with before surgery, CD62p, CD63, miR-223, PAC-1, platelet membrane glycoprotein IIb/IIIa complex, and gelsolin levels markedly decreased in both groups 4 weeksafter surgery (P < .05). The platelet activation index and platelet miR-223 and gelsolin levels were significantly lower in the study group than in the control group 4 weeks after surgery (P < .05). The overall platelet inhibition effect was significantly better in the study group than in the control group (P < .05). Compared with before surgery, the left ventricular ejection fraction and stroke volume were significantly increased, and the leftventricular end-diastolic volume and left ventricular end-diastolic diameter significantly decreased in both groups 4 weeks after surgery (P < .05). No significant differences were found between the 2 groups in terms of the incidence of bleeding events or MACE (P > .05).

Conclusion: Ticagrelor is more effective thanclopidogrel for platelet inhibition after PCI in patients with ACS and is worthy of clinical recommendation.

Disclaimer:

Lupin makes no representation or warranty of any kind, expressed or implied, regarding the accuracy, adequacy, validity, reliability, availability, or completeness of any scientific information shared by the HCP on the STAR UPDATE podcast. You should not allow the contents of this to substitute for your own medical judgment, which you should exercise in evaluating the information on this website.

View Details

Factors associated with complications in ST-elevation myocardial infarction: a single-center experience

BMC Cardiovasc Disord 2023 Sep 19;23(1):468.

Abstract

Background: ST-elevation myocardial infarction (STEMI) is a major public health problem. This study aimed to determine theprevalence and identify the determinants of STEMI-related complications in the Cardiology Intensive Care Unit of the Sud Francilien Hospital Center (SFHC).

Methods: We retrospectively analyzed the data of 315patients with STEMI aged ≥ 18 years. Logistic regression was used to identify factors independently associated with the occurrence of complications.

Results: Overall, 315 patients aged 61.7 ± 13.4years, of whom 261 were men, had STEMI during the study period. The hospital frequency of STEMI was 12.7%. Arrhythmias and acute heart failure were the main complications. Age ≥ 75 years (adjusted odds ratio [aOR], 5.18; 95% confidenceinterval [CI], 3.92-8.75), hypertension (aOR, 3.38; 95% CI, 1.68-5.82), and cigarette smoking (aOR, 3.52; 95% CI, 1.69-7.33) were independent determinants of acute heart failure. Meanwhile, diabetes mellitus (aOR, 1.74; 95% CI, 1.09-3.37), history of atrial fibrillation (aOR, 2.79; 95% CI, 1.66-4.76), history of stroke or transient ischemic attack (aOR, 1.99; 95% CI, 1.31-2.89),and low high-density lipoprotein-cholesterol (HDL-C) levels (aOR, 3.70; 95% CI, 1.08-6.64) were independent determinants of arrhythmias.

Conclusion: STEMI is a frequent condition at SFHC andis often complicated by acute heart failure and arrhythmias. Patients aged ≥ 75 years, those with hypertension or diabetes mellitus, smokers, those with a history of atrial fibrillation or stroke, and those with low HDL-C levels require careful monitoring for the early diagnosis and management of thesecomplications.

Disclaimer:

Lupin makes no representation or warranty of any kind,expressed or implied, regarding the accuracy, adequacy, validity, reliability, availability, or completeness of any scientific information shared by the HCP on the STAR UPDATE podcast. You should not allow the contents of this to substitute for your own medical judgment, which you should exercise inevaluating the information on this website.

View Details

Short-Term DAPT and DAPT De-Escalation Strategies for Patients With Acute Coronary Syndromes: A Systematic Review and Network Meta-Analysis

Circ Cardiovasc Interv. 2023 Sep;16(9):e013242

Abstract

Background: Short-term (≤6 months) dual antiplatelettherapy (DAPT) and DAPT de-escalation become attractive for patients with acute coronary syndrome.

Methods: A systemic search identified randomizedcontrolled trials that included patients with acute coronary syndrome treated using (1) standard DAPT (12 months) with clopidogrel, prasugrel (standard/low dose), or ticagrelor; (2) extended DAPT (≥18 months); (3) short-term DAPT (≤6months) followed by P2Y12 inhibitor or aspirin; (4) 12-month DAPT with unguided de-escalation from potent P2Y12 inhibitors to low-dose potent P2Y12 inhibitor or clopidogrel at 1 month; and (5) guided selection DAPT with genotype or plateletfunction tests. The primary efficacy outcome (major adverse cardiovascular events) was a composite of cardiovascular death, myocardial infarction, or stroke. The primary safety outcome was major or minor bleeding.

Results: This meta-analysis included 32 randomizedcontrolled trials with 103 497 patients. While there were no differences in efficacy between short, unguided de-escalation and guided selection strategies, unguided de-escalation was associated with reduced risk of major adversecardiovascular events compared with standard DAPT with clopidogrel or ticagrelor (hazard ratio [95% CI], 0.67 [0.49-0.93] and 0.68 [0.50-0.93]). Both short DAPT followed by P2Y12 inhibitor and unguided de-escalation wereassociated with reduced risks in safety compared with other strategies, including guided selection (hazard ratio [95% CI], 0.66 [0.47-0.93] and 0.48 [0.33-0.71]). Short DAPT followed by a P2Y12 inhibitor was associated with reduced risk of major bleeding and all-cause death compared with standard, extendedDAPT (eg, versus DAPT with clopidogrel; hazard ratio [95% CI], 0.64 [0.42-0.97]and 0.60 [0.44-0.82]). By rankogram, unguided de-escalation strategy was the safest and most effective strategy in reducing major adverse cardiovascular events and major or minor bleeding while short DAPT followed by P2Y12 inhibitorwas ranked the best for major bleeding and all-cause death.

Conclusions: In patients with acute coronarysyndrome, unguided de-escalation was associated with the lowest risk of major adverse cardiovascular events and major or minor bleeding outcomes, while short DAPT followed by P2Y12 inhibitor was associated with the lowest risk of majorbleeding and all-cause death.

Disclaimer:

Lupin makes no representation or warranty of any kind,expressed or implied, regarding the accuracy, adequacy, validity, reliability, availability, or completeness of any scientific information shared by the HCP on the STAR UPDATE podcast. You should not allow the contents of this tosubstitute for your own medical judgment, which you should exercise in evaluating the information on this website.

View Details

Early Effects of Ticagrelor Versus Clopidogrel on Peripheral Endothelial Function After Non-ST-Elevation Acute Coronary Syndrome and Assessment of Its Relationship With Coronary Microvascular Function

Am J Cardiol. 2023 Aug 15; 201:16-24

Abstract

Peripheral endothelial dysfunction is an independent predictor of adverse long-term prognosis after acute coronary syndrome. Data are lacking on the effects of oral P2Y12-inhibitors on peripheral endothelial function in non-ST-elevation acute coronary syndrome (NSTEACS). Furthermore, the relation between peripheral endothelial function and invasive indexes of coronary microvascular function in NSTEACS is unclear. Between March 2018 and July 2020, hospitalized patientswith NSTEACS were randomized (1:1) to ticagrelor or clopidogrel. Peripheral endothelial function was assessed with brachial artery flow-mediated vasodilation (FMD). Invasive indexes of coronary microvascular function were obtained using an intracoronary pressure-temperature sensor-tipped wire. In 70 patients included, mean age was 58.6 years, 78.6% (n = 55) were male and 20% (n= 14) had diabetes mellitus. Compared with clopidogrel, ticagrelor significantly improved FMD (14.2 ± 5.4% vs 8.9 ± 5.3%, p <0.001) after a median treatment time of 41.2 hours. The FMD was significantly correlated withthe index of microcirculatory resistance (IMR) measured in the infarct-related artery (r = -0.38, p = 0.001), with a stronger correlation found in those who did not have percutaneous coronary intervention (r = -0.52, p = 0.03). Using receiver operating characteristic curve analysis, an FMD of 8.2% identified an IMR of >34 as the threshold, with 77.6% sensitivity and 52.4% specificity. In patients who did not have a percutaneous coronary intervention, an FMD of 11.49% identified an IMR of >34 with 84.6% sensitivity and 80% specificity.

Conclusion

Ticagrelor significantly improved peripheral endothelialfunction compared with clopidogrel in patients with NSTEACS. There was a significant correlation between brachial artery FMD and IMR of the infarct-related artery.

Disclaimer:

Lupin makes no representation or warranty of any kind, expressed or implied, regarding the accuracy, adequacy, validity, reliability, availability, or completeness of any scientific information shared by the HCP on the STAR UPDATE podcast. You should not allow the contents of this to substitute for your own medical judgment, which you should exercise in evaluating the information on this website.

View Details

Prognostic factors in young patients with ST-segment elevation myocardial infarction

Coron Artery Dis. 2023 Aug 1;34(5):298-305.

Abstract

Objective: The prognostic factors of young patients aged ≤40 years with ST-segment elevation myocardial infarction (STEMI) remain unclear. This study explored risk factors that may affect the 1-year prognosis of young STEMI patients by analyzing patient data of baseline, clinical regimen, and secondary prevention.

Methods: Baseline and clinical data were collected from 420 STEMI patients aged ≤40 years. One year of follow-up was performed to record and compare the differences in data between patients with and without adverse events. Binary logistic regression analysis with controls for confounding factors was used to evaluate prognosis-related independent factors.

Results: The overall incidence of cardiovascular adverse events was 15.95%. Comparison of the subgroups revealed that regardless of adjustment for confounding factors, prognoses of the patients were affected by the following factors: BMI, marital status, serum apolipoprotein(a) (ApoA) levels, number of diseased vessels,treatment regimen, compliance of secondary prevention, improvement of lifestyle, and adjusted comorbidities ( P < 0.05). Independent analysis of adverse events revealed that BMI, number of diseased vessels, and compliance of secondary prevention were independent factors of recurrent acute myocardial infarction in patients. Serum ApoA level, treatment regimen, and compliance of secondary prevention were independent influence factors of heart failure in patients. Marital status and serum ApoA level were independent factors of malignant arrhythmias in patients. BMI, compliance of secondary prevention, andimprovement of lifestyle were independent factors of cardiac death in patients.

Conclusion: This study determined the influential factors for the prognosis of STEMI patients aged ≤40 years as follows: BMI, marital status, comorbidities, number of diseased vessels, regimen, compliance of secondary prevention, and improvement of lifestyle. The risk of cardiovascular adverse events may be reduced by modulating the influential factors.

Disclaimer:

Lupin makes no representation or warranty of any kind, expressed or implied, regarding the accuracy, adequacy, validity, reliability, availability, or completeness of any scientific information shared by the HCP on the STAR UPDATE podcast. You should not allow the contents of this to substitute for your own medical judgment, which you should exercise in evaluating the information on this website.

View Details

Metoprolol or Verapamil in the Managementof Patients With Hypertrophic Cardiomyopathy: A Systematic Review Cureus. 2023 Aug 9;15(8):e43197

Abstract

Hypertrophic cardiomyopathy (HCM) is the most common geneticheart disease and is a prevalent cause of sudden cardiac death (SCD). This study aims to establish the benefits and therapeutic value metoprolol or verapamil offer to patients who suffer from symptoms caused by HCM, with regard to resolving left ventricular outflow tract obstruction (LVOTO), as well as improving a patient's quality of life and reducing symptoms. We conducted a systematic review to find clinical studies that described the use of metoprolol or verapamil in the management of HCM. Three databases were analyzed forstudies, PubMed, Google Scholar, and ScienceDirect. We discovered 6,260 potentially eligible records across all the databases. According to our eligibility criteria, we included four studies in this review. Metoprololshowed median left ventricular outflow tract (LVOT) gradients of 25 mm Hg versus 72 mm Hg (P = 0.007) at rest, 28 mm Hg versus 62 mm Hg (P < 0.001) at peak exercise, and 45 mm Hg versus 115 mm Hg (P < 0.001) post-exercise. Verapamil also showed a statistically significant increase in exercise capacity. Both drugs have been shown to be safe to use with a good side effect profile; however, metoprolol was better tolerated in the patient population that was tested in the studies collected. In this study, metoprolol was effective in reducing LVOT and improving the quality of life in patients, while verapamil showed variable effects on both exercise capacity and baseline hemodynamics.

Disclaimer:

Lupin makes no representation or warranty of any kind, expressed or implied, regarding the accuracy, adequacy, validity, reliability, availability, or completeness of any scientific information shared by the HCP on the STAR UPDATE podcast. You should not allow the contents of this to substitute for your own medical judgment, which you should exercise in evaluating the information on this website.

View Details

Comparative Effectiveness of Long-Term Maintenance Beta-Blocker Therapy After Acute Myocardial Infarction in Stable, Optimally Treated Patients Undergoing Percutaneous Coronary Intervention

J Am Heart Asso. 2023 Aug;12(15): e028976

Abstract

BackgroundThe benefits of long-term maintenance beta-blocker (BB) therapy in patients with acute myocardial infarction (AMI) undergoing percutaneous coronary intervention (PCI) have not been well established. Methods and Results Using the Korean nationwide registry, a total of 7159 patients with AMI treated with PCI who received BBs at discharge and were free from death or cardiovascular events for 3 months after PCI were included in the analysis. Patients weredivided into 4 groups according to BB maintenance duration: <12 months, 12 to <24 months, 24 to <36 months, and ≥36 months. The primary outcome was the composite of all-cause death, recurrent MI, heart failure, or hospitalization for unstable angina. During a mean 5.0±2.8 years of follow-up, over half of patients with AMI (52.5%) continued BB therapy beyond 3 years following PCI. After propensity score matching and propensity score marginal mean weighting through stratification, a stepwise inverse correlation was noted between BB duration and risk of the primary outcome (<12 months: hazardratio [HR], 2.19 [95% CI, 1.95-2.46]; 12 to <24 months: HR, 2.10 [95% CI,1.81-2.43];, and 24 to <36 months: HR, 1.68 [95%CI, 1.45-1.94]; reference: ≥36 months). In a 3-year landmark analysis, BB use for <36 months was associated with an increased risk of the primary outcome (adjusted HR, 1.59 [95% CI, 1.37-1.85]) compared with BB use for ≥36 months.

Conclusion

Among stabilized patients with AMI following PCI, longer maintenance BB therapy, especially for >36 months, was associated with better clinical outcomes. These findings might imply that a better prognosis can be expected if patients with AMI maintain BB therapy for ≥36 months after PCI.

Disclaimer:

Lupin makes no representation or warranty of any kind, expressed or implied, regarding the accuracy, adequacy, validity, reliability, availability, or completeness of any scientific information shared by the HCP on the STAR UPDATE podcast. You should not allow the contents of this to substitute for your own medical judgment, which you should exercise in evaluating the information on this website.

View Details

The new report of the ESH 2023 guideline includes a greater emphasis on out-of-office BP measurements, addition of potassium supplementation as a lifestyle recommendation, and gives more explicit advice for the use of beta blockers as initial antihypertensive drug therapy. Increased resting heart rate (>80 bpm) is common in hypertension, in which it reflects an increased sympathetic activity. A progressive increase in resting heart rate is accompanied by a progressive increase in the risk of AF, HF and mortality both in the general population and in hypertensive patients. Although in hypertension, the advantage of reducing heart rate is limited to post hoc analysis of RCTs, the available evidence makes treated hypertensive patients with an increased heart rate a clinical phenotype supporting the use of BBs. RCTs and meta-analyses have demonstrated that when compared with placebo, first-generation and second-generation BBs like propranolol, atenolol and metoprolol significantly reduce the risk of stroke, HF and major CV events in hypertensive patients. BBs are recommended in patients with HF, angina, post-MI, AF or in younger hypertensive women of child-bearing potential or planning pregnancy. RCTs with carvedilol, bisoprolol, metoprolol and nebivolol showed improved outcomes in patients with HFrEF.In addition to their compelling use as GDMT in specific diseases, BBs exhibit favourable effects in about 50 clinical conditions including various cardiac diseases less or not related to hypertension, other vascular conditions and non-CV diseases

Reference: 2023 ESH Guidelines for the management of arterial hypertension

View Details

P2Y12 Inhibitor or Aspirin Monotherapy for Secondary Prevention of Coronary Events

J Am Coll Cardiol. 2023 Jul, 82 (2) 89–105

Abstract

Background

Aspirin is the only antiplatelet agent with a Class I recommendation for long-term prevention of cardiovascular events in patients with coronary artery disease (CAD). There is inconsistent evidence on how it compares with alternative antiplatelet agents.

Objectives

This study compared P2Y12 inhibitor monotherapy vs aspirin in patients with CAD.

Methods

We conducted a patient-level meta-analysis of randomized trials comparing P2Y12 inhibitor monotherapy vs aspirin monotherapy for the prevention of cardiovascular events in patients with established CAD. The primary outcome was the composite of cardiovascular death, myocardial infarction, and stroke. Prespecified key secondary outcomes were major bleeding and net adverse clinical events (the composite of the primary outcome and major bleeding). Data were pooled in a 1-step meta-analysis.

Results

Patient-level data were obtained from 7 trials. Overall, 24,325 participants were available for analysis, including 12,178 patients assigned to receive P2Y12 inhibitor monotherapy (clopidogrel in 7,545 [62.0%], ticagrelor in 4,633 [38.0%]) and 12,147 assigned to receive aspirin. Risk of the primary outcome was lower with P2Y12 inhibitor monotherapy compared with aspirin over 2 years (HR: 0.88; 95% CI: 0.79-0.97; P = 0.012), mainly owing to less myocardial infarction (HR: 0.77; 95% CI: 0.66-0.90; P < 0.001). Major bleeding was similar (HR: 0.87; 95% CI: 0.70-1.09; P = 0.23) and net adverse clinical events were lower (HR: 0.89; 95% CI: 0.81-0.98; P = 0.020) with P2Y12 inhibitors. The treatment effect was consistent across prespecified subgroups and types of P2Y12 inhibitors.

Conclusions

Given its superior efficacy and similar overall safety, P2Y12 inhibitor monotherapy might be preferred over aspirin monotherapy for long-term secondary prevention in patients with established CAD. (P2Y12 Inhibitor or Aspirin Monotherapy as Secondary Prevention in Patients With Coronary Artery Disease: An Individual Patient Data Meta-Analysis of Randomized Trials [PANTHER collaborative initiative]; CRD42021290774

Disclaimer:

Lupin makes no representation or warranty of any kind, expressed or implied, regarding the accuracy, adequacy, validity, reliability, availability, or completeness of any scientific information shared by the HCP on the STAR UPDATE podcast. You should not allow the contents of this to substitute for your own medical judgment, which you should exercise in evaluating the information on this website.

View Details

Impact of Diabetes Mellitus on the Benefit of β-Blocker Therapy After Myocardial Infarction

Am JCardiol 2023 Jul 1;198:124-132. doi:10.1016/j.amjcard.2023.04.022.

Abstract

Beta blockers are uniformly recommended for all patients after myocardial infarction (MI), including those with diabetes mellitus (DM).

This study assesses the impact of β-blocker type and dosing on survival in patients with DM after MI. A cohort of 6,682 patients in the Outcomes of Beta-blocker Therapy After Myocardial Infarction registry were discharged after MI. In this cohort, 2,137 patients had DM (32%). Beta-blocker dose was indexed to the target daily dose used in randomized clinical trials and reported as percentage. Dosage groups were: no β blocker, >0% to 12.5%, >12.5% to 25%, >25% to 50%, and >50% of the target dose. The overall mean discharge β-blocker dose in patients with DM was 42.7 ± 34.1% versus 35.9 ± 27.4% in patients without DM (p <0.0001). Patients with DM were prescribed carvedilol at a higher rate than those without DM (27.8% vs 19.6%). The 3-year mortality estimates were 24.4% and 12.8% for patients with DM versus without DM (p <0.0001), respectively, with an unadjusted hazard ratio = 1.820 (confidence interval 1.587 to 2.086, p <0.0001). Patients with DM in the >12.5% to 25% dose category had the highest survival rates, whereas patients in the >50% dose had the lowest survival rate among patients discharged on β blockers (p <0.0001). In the multivariable analysis among patients with DM after MI, all β-blocker dose categories demonstrated lower mortality than no therapy; however, only the >12.5% to 25% dose had a statistically significant hazard ratio 0.450 (95% confidence interval 0.224 to 0.907, p = 0.025). In patients with DM, there was no statistically significant difference in 3-year mortality among those treated with metoprolol versus carvedilol.

In conclusion, our analysis in patients with DM after MI suggested a survival benefit from β-blocker therapy, with no apparent advantage to high- versus low-dose β-blocker therapy; although, physicians tended to prescribe higher doses in patients with DM. There was no survival benefit for carvedilol over metoprolol in patients with DM.

Disclaimer:

Lupin makes no representation or warranty of any kind, expressed or implied, regarding the accuracy, adequacy, validity, reliability, availability, or completeness of any scientific information shared by the HCP on the STAR UPDATE podcast. You should not allow the contents of this to substitute for your own medical judgment, which you should exercise in evaluating the information on this website.

View Details

Clinical risk factors and outcomes of young patients with acute ST-segment elevation myocardial infarction: a retrospective study

Liang et al. BMC Cardiovascular Disorders (2023), https://doi.org/10.1186/s12872-023-03392-8

Abstract

Background

This study aimed to analysis the clinical characteristics and prognosis of acute STEMI in patients aged ≤ 45 years.

Methods

Seven hundred and one patients with STEMI from Liaocheng People’s Hospital from January 2018 to March 2021 were included in this study. Clinical characteristics, management, and outcomes (average follow-up: 11.5 months) were compared between patients aged ≤ 45 years and those aged > 45 years.

Results

Of the patients with STEMI who underwent primary percutaneous coronary intervention, 108 (15.4%) were aged ≤ 45 years. Compared to the older group, the younger patient group included more males, current smokers, and those with alcohol use disorder (AUD) or a family history of ischaemic heart disease (IHD). The culprit vessel in young patients was the left anterior descending (LAD) artery (60% vs. 45.9%, P = 0.031), which may have been due to smoking (odds ratio, 3.5; 95% confidence interval: 1.12–10.98, P = 0.042). Additionally, young patients presented with higher low-density lipoprotein and lower high-density lipoprotein levels than older patients; uric acid levels were also significantly higher in younger patients than that in the older group. Diabetes showed a trend toward major adverse cardiovascular events (MACE) in both groups; age and sex were both independent predictors of MACE in older patients.

Conclusion

More patients who were smokers, had AUD, or a family history of IHD were present in the young patient group. Hyperuricaemia (but not dyslipidaemia) was a prevalent risk factor in patients aged ≤ 45 years. Diabetes should be controlled to reduce cardiovascular events in young patients.

View Details

Frequency of New Onset Atrial Fibrillation in Patients Presenting with ST-Segment Elevation Myocardial Infarction

DOI: https://doi.org/10.53350/pjmhs2023176112Abstract

Aim: To study the magnitude of atrial fibrillation in patients with ST segment elevation myocardial infarction.

Methodology: Two hundred and thirty-six patients were selected through non-probability, consecutive sampling technique. Patients were divided into Group 1 who did not develop AF while group 2 included the new cases of AF during in-hospital stay for STEMI. All patients underwent clinical examinations, echocardiography, angiography and percutaneous coronary intervention.

Results: Forty five cases with an average age of 71±14 years developed atrial fibrillation. Female population 25(60%) was at higher risk than male 17(40%). In AF group, 22(53.3%) cases of dyslipidemia, 11(26.1%) cases of chronic renal disease, 4(8.8%) cases of prior myocardial infarction, 14(33.3%) cases of diabetes and a single case (2.2%) of implantable cardiac-defibrillator were observed when compared with the non-AF group.

Practical Implication: In-hospital complications are also highly associated with AF which may result in high Incidents of mortality.

Conclusion: Aging, comorbidities and inferior wall MI are the independent predictors of AF. In-hospital complications are associated with AF which may result in high incidents of mortality. Early diagnosis of STEMI patients with a high risk of developing AF is necessary to reduce the morbidity and mortality.

Disclaimer:

Lupin makes no representation or warranty of any kind, expressed or implied, regarding the accuracy, adequacy, validity, reliability, availability, or completeness of any scientific information shared by the HCP on the STAR UPDATE podcast. You should not allow the contents of this to substitute for your own medical judgment, which you should exercise in evaluating the information on this website.

View Details

The prognostic value of myocardial salvage index by cardiac magnetic resonance in ST-segment elevation myocardial infarction patients: a systematic review and meta-analysis.

2023 Jun 16.doi: 10.1007/s00330-023-09739-1.

Abstract

Objective: To assess the prognostic value of myocardial salvage index (MSI) by cardiac magnetic resonance (CMR) in ST-segment elevation myocardial infarction (STEMI) patients.

Methods: We systematically searched PubMed, Embase, Web of Science, Cochrane Central, China National Knowledge Infrastructure, and Wanfang Data to identify primary studies reporting MSI in STEMI patients with major adverse cardiovascular events (MACE) comprised of death, myocardial reinfarction, and congestive heart failure. The MSI and MACE rates were pooled. The bias of risk was assessed using the Quality In Prognosis Studies tool. The evidence level was rated based on the meta-analysis of hazard ratio (HR) and 95% confidence interval (CI) of MSI for predicting MACE.

Results: Eighteen studies were included covering twelve unique cohorts. Eleven cohorts measured MSI using T2-weighted imaging and T1-weighted late gadolinium enhancement, while one cohort applied T2-mapping and T1-mapping. The pooled MSI (95% CI) was 44% (39 to 49%; 11 studies, 2946 patients), and the pooled MACE rate (95% CI) was 10% (7 to 14%; 12 studies, 311/3011 events/patients). Seven prognostic studies overall showed low risk of bias. The HR (95% CI) per 1% increase of MSI for MACE was 0.95 (0.92 to 0.98; 5 studies, 150/885 events/patients), and HR (95% CI) of MSI < median versus MSI > median for MACE was 5.62 (3.74 to 8.43; 6 studies, 166/1570 events/patients), both rated as weak evidence.

Conclusions: MSI presents potential in predicting MACE in STEMI patients. The prognostic value of MSI using advanced CMR techniques for adverse cardiovascular events needs further investigation.

Disclaimer:

Lupin makes no representation or warranty of any kind, expressed or implied, regarding the accuracy, adequacy, validity, reliability, availability, or completeness of any scientific information shared by the HCP on the STAR UPDATE podcast. You should not allow the contents of this to substitute for your own medical judgment, which you should exercise in evaluating the information on this website.

View Details

Association between the beta-blockers, calcium channel blockers, all-cause mortality and length of hospitalization in patients with heart failure with preserved ejection fraction: A meta-analysis of randomized controlled trials.

2023 Jun 4. doi: 10.1002/clc.24058.

Abstract Purpose: To establish an association between beta-blockers (BBs), calcium channel blockers (CCBs), all-cause mortality, and hospitalization in patients with Heart failure with preserved Ejection Fraction (HFpEF).

Methods: The present meta-analysis has been performed as per the guidelines of (PRISMA). An inclusive literature search was made without any limitations on language using the electronic databases Cochrane Library, EMBASE, and PubMed up to November 2022. The outcomes evaluated in this meta-analysis involved all-cause mortality and hospitalization due to heart failure. The number of patients with HFpEF and their positive outcomes was extracted and analyzed using RevMan software.

Results: In total, 10 articles were included in the present meta-analysis, with a pooled sample size of 12 940 HFpEF patients. In comparison with placebo, both BB and CCB substantially reduced the risk of all-cause mortality and hospitalization. However, BB are more effective because they provide a significant reduction in all-cause mortality (risk ratio (RR) = 0.60; 95% confidence interval [CI] = 0.43-0.83; p = .002] and hospitalization (RR = 0.54; 95% CI = 0.37-0.80; p =.002) as compared with CCB with a risk ratio of all-cause mortality (RR = 0.77; 95% CI = 0.60-0.98; p = .03) and hospitalization (RR = 0.63; 95% CI = 0.44-0.90; p < .00001). A random-effects model was used because of high heterogeneity between the studies (I2 > 70%).

Conclusions: The current meta-analysis suggests that BBs were more beneficial than CCB in reducing all-cause mortality and hospitalization duration in patients with HFpEF.

Disclaimer:

Lupin makes no representation or warranty of any kind, expressed or implied, regarding the accuracy, adequacy, validity, reliability, availability, or completeness of any scientific information shared by the HCP on the STAR UPDATE podcast. You should not allow the contents of this to substitute for your own medical judgment, which you should exercise in evaluating the information on this website.

View Details

Ticagrelor with or without aspirin in high-risk patients with anaemia undergoing percutaneous coronary intervention: a subgroup analysis of the TWILIGHT trial

2023 Jun 2;9(4):328-336. doi:10.1093/ehjcvp/pvad006.

Abstract

Aim: The aim of this study was to assess the effect of ticagrelor monotherapy among high-risk patients with anaemia undergoing percutaneous coronary intervention (PCI).

Methods and results: In the TWILIGHT (Ticagrelor with Aspirin or Alone in High-Risk Patients after Coronary Intervention) trial, after 3 months of ticagrelor plus aspirin, high-risk patients were maintained on ticagrelor and randomized to aspirin or placebo for 1 year. Anaemia was defined as haemoglobin <13 g/dL for men and <12 g/dL for women. The primary endpoint was Bleeding Academic Research Consortium (BARC) 2, 3, or 5 bleeding. The key secondary endpoint was a composite of all-cause death, myocardial infarction, or stroke.Out of 6828 patients, 1329 (19.5%) had anaemia and were more likely to have comorbidities, multivessel disease, and to experience bleeding or ischaemic complications than non-anaemic patients. Among anaemic patients, BARC 2, 3, or 5 bleeding occurred less frequently with ticagrelor monotherapy than with ticagrelor plus aspirin [6.4% vs. 10.7%; hazard ratio (HR) 0.60; 95% confidence interval (CI) 0.41-0.88; P =0.009]; the rate of the key secondary endpoint was similar in the two arms (5.2% vs. 4.8%; HR 1.07; 95% CI 0.66-1.74; P = 0.779). These effects were consistent in patients without anaemia (interaction P values 0.671 and 0.835, respectively).

Conclusion: In high-risk patients undergoing PCI, ticagrelor monotherapy after 3 months of ticagrelor-based dual antiplatelet therapy was associated with a reduced risk of clinically relevant bleeding without any increase in ischaemic events irrespective of anaemia status (TWILIGHT: NCT02270242).

Disclaimer: Lupin makes no representation or warranty of any kind, expressed or implied, regarding the accuracy, adequacy, validity, reliability, availability, or completeness of any scientific information shared by the HCP on the STAR UPDATE podcast. You should not allow the contents of this to substitute for your own medical judgment, which you should exercise in evaluating the information on this website.

View Details

Impact of Diabetes Mellitus on Benefit of β-Blocker Therapy AfterMyocardial Infarction

https://doi.org/10.1016/j.amjcard.2023.04.022

Abstract

Background:Beta blockers are uniformly recommended for all patients after myocardial infarction (MI), including thosewith diabetes mellitus (DM). This study assesses the impact of β-blocker typeand dosing on survival in patients with DM after MI. Methods:A cohort of 6,682 patients in theOutcomes of Beta-blocker Therapy After Myocardial Infarctionregistry were discharged after MI. In this cohort, 2,137 patients had DM (32%).Beta-blocker dose was indexed to the target daily dose used in randomizedclinical trials and reported as percentage. Dosage groups were: no β blocker,>0% to 12.5%, >12.5% to 25%, >25% to 50%, and >50% of the targetdose. The overall mean discharge β-blocker dose in patients with DM was 42.7 ±34.1% versus 35.9 ± 27.4% in patients without DM (p <0.0001). Results:Patients with DM were prescribed carvedilol ata higher rate than those without DM (27.8% vs 19.6%). The 3-year mortalityestimates were 24.4% and 12.8% for patients with DM versus without DM (p<0.0001), respectively, with an unadjusted hazard ratio = 1.820(confidence interval 1.587 to 2.086, p <0.0001). Patients with DM in the>12.5% to 25% dose category had the highest survival rates, whereas patientsin the >50% dose had the lowest survival rate among patients discharged on βblockers (p <0.0001). In the multivariable analysis among patients with DMafter MI, all β-blocker dose categories demonstrated lower mortality than notherapy; however, only the >12.5% to 25% dose had a statisticallysignificant hazard ratio 0.450 (95% confidence interval 0.224 to 0.907,p = 0.025). In patients with DM, there was no statisticallysignificant difference in 3-year mortality among those treated with metoprololversus carvedilol. Conclusions:In conclusion, our analysis inpatients with DM after MI suggested a survival benefit from β-blocker therapy,with no apparent advantage to high- versus low-dose β-blocker therapy;although, physicians tended to prescribe higher doses in patients with DM.There was no survival benefit for carvedilol over metoprolol in patients withDM.

Disclaimer: Lupin makes no representation or warranty of any kind, expressed or implied, regarding the accuracy, adequacy, validity, reliability, availability, or completeness of any scientific information shared by the HCP on the STAR UPDATE podcast. You should not allow the contents of this to substitute for your own medical judgment, which you should exercise in evaluating the information on this website.

View Details

Heart failure pharmacological treatments and outcomes in heart failure with mildly reducedejection fraction

https://doi.org/10.1093/ehjcvp/pvad036

Abstract

Background:

Guideline recommendations for thetreatment of heart failure with mildly reduced ejection fraction (HFmrEF)derive from small subgroups in post-hoc analyses of randomized trials.

Objectives:

We investigated predictors ofrenin-angiotensin system inhibitors/angiotensin receptor neprilysin inhibitors(RASI/ARNI) and beta-blockers use, and the associations between thesemedications and mortality/morbidity in a large real-world cohort with HFmrEF.

Methods:

Patients with HFmrEF (EF 40–49%) fromthe Swedish HF Registry were included. The associations between medications andcardiovascular (CV) mortality/HF hospitalization (HFH) and all-cause mortalitywere assessed through Cox regressions in a 1:1 propensity score-matched cohort.A positive control analysis was performed in patients withEF < 40%, while a negative control outcome analysis hadcancer-related hospitalization as endpoint.

Results:

Of 12 421 patients with HFmrEF,84% received RASI/ARNI and 88% beta-blockers. Shared independent predictors ofRASI/ARNI and beta-blockers use were younger age, being an outpatient,follow-up in specialty care, hypertension. In the matched cohorts, use of bothRASI/ARNI and beta-blocker use was separately associated with lower risk of CVmortality/HFH (HR = 0.90, 95%CI:0.83–0.98 and HR = 0.82,95%CI:0.74–0.90, respectively) and of all-cause mortality (HR = 0.75,95%CI:0.69–0.81 and HR = 0.79, 95%CI:0.72–0.87, respectively).Results were consistent at the positive control analysis, and there were noassociations between treatment use and the negative control outcome.

Conclusions:

RASI/ARNI and beta-blockers wereextensively used in this large real-world cohort with HFmrEF. Their use wassafe since associated with lower mortality and morbidity. Our findings confirmin the real world evidence from previous post-hoc analyses of trials, andrepresent a further call for implementing guideline recommendations.

Disclaimer: Lupin makes no representation or warranty of any kind, expressed or implied, regarding the accuracy, adequacy, validity, reliability, availability, or completeness of any scientific information shared by the HCP on the STAR UPDATE podcast. You should not allow the contents of this to substitute for your own medical judgment, which you should exercise in evaluating the information on this website.

View Details

Biomarkers of Thrombotic Status Predict Spontaneous Reperfusionin Patients With ST-Segment Elevation Myocardial Infarction https://doi.org/10.1016/j.jacc.2023.03.388

AbstractBackground:Spontaneous reperfusion, seen in ∼20% of patients withST-segment elevation myocardial infarction (STEMI), manifests as normalepicardial flow in the infarct-related artery, with or without ST-segmentresolution, before percutaneous coronary intervention (PCI). The drivers mediating this are unknown.

Objectives:

The authors sought to relate spontaneous reperfusion to thethrombotic profile.

Methods:

In a prospective study, blood from STEMI patients(n = 801) was tested pre-PCI to assess in vitro, point-of-care, occlusion times (OT) andendogenous lysis times (LT). Spontaneous reperfusion was defined as infarct-relatedartery Thrombolysis In MyocardialInfarction flow grade 3 before PCI. Patients were followed for majorcardiovascular events (death, myocardial infarction, or stroke).

Results:

Spontaneous reperfusion was associated with a longerOT (435 seconds vs 366 seconds; P < 0.001) and a shorter LT (1,257 seconds vs 1,616seconds; P < 0.001), lower troponin, and better left ventricular function. LT was superior toOT for predicting spontaneous reperfusion (area under the curve for LT: 0.707;95% CI: 0.661-0.753; area under the curve for OT: 0.629;95% CI: 0.581-0.677). Among patients with spontaneous reperfusion, thosewith complete, vs partial ST-segment resolution, had a longer OT (P = 0.002) and a shorter LT (P < 0.001). Spontaneous reperfusion wasunrelated to clinical characteristics or pain-to-angiography times. Over 4years, patients with spontaneous reperfusion experienced fewer major adversecardiovascular events than those without (4.1% vs 10.6%; P = 0.013), especially in those with bothspontaneous reperfusion and complete ST-segment resolution (1.5% vs10.1%; P = 0.029).

Conclusions:

We demonstrate a novel hematological signature inSTEMI patients with spontaneous reperfusion, namely, decreased platelet reactivity andfaster endogenous fibrinolysis, relating tosmaller infarcts and improved survival. This finding indicates a role formodulating thrombotic status early after STEMI onset, to facilitate spontaneousreperfusion and improve outcomes.

Disclaimer: Lupin makes no representation or warranty of any kind, expressed or implied, regarding the accuracy, adequacy, validity, reliability, availability, or completeness of any scientific information shared by the HCP on the STAR UPDATE podcast. You should not allow the contents of this to substitute for your own medical judgment, which you should exercise in evaluating the information on this website.

MethodsResultsConclusions

View Details

Ticagrelor for patients undergoing coronary artery bypass grafting: A meta-analysis ofrandomized controlled trials

2023 May;38(4):698-705. doi: 10.1177/02676591221076284.

Abstract

Objective: Ticagrelor may be an alternative to aspirin as it providesrobust and consistent platelet inhibition. However, the effect of ticagrelortreatment in patients undergoing coronary artery bypass grafting (CABG) has notbeen well confirmed. We conducted a meta-analysis to appraise whether ticagrelortherapy affects outcomes in CABG patients.

Methods: We searched PubMed, Embase, EBSCO, and Cochrane databases fromits inception up to 4 December 2020 for randomized controlled trials thatassessed ticagrelor versus non-ticagrelor in patients undergoing CABG. Theprimary outcome was the incidence of saphenous vein graft (SVG) occlusion at 1year after CABG. Secondary outcomes were SVG occlusion at 7 days, major adversecardiovascular events (MACE), and bleeding requiring reoperation.

Results: Seven trials including 4305 patients (2153 randomized toticagrelor therapy and 2152 to non-ticagrelor therapy) were included.One-hundred and thirty of 1140 patients (11.4%) randomized to the ticagrelorgroup versus 175 of 1220 patients (14.3%) randomized to the non-ticagrelorgroup experienced SVG occlusion at 1 year after CABG. Compared to the controlgroup, ticagrelor therapy yielded a significantly lower risk of SVG occlusion[RR 0.79 (0.64-0.97), p = 0.03]. In the subgroup analysis,ticagrelor plus aspirin compared with aspirin alone did not decrease the riskof SVG occlusion after 1 year [RR 0.65 (0.40-1.07), p = 0.09].There was no difference in the incidence of SVG occlusion at 7 days [RR 0.67(0.42-1.06), p = 0.09], MACE up to 1 year [RR 0.99 (0.81-1.21), p =0.90], or bleeding requiring reoperation [RR 1.16 (0.80-1.70), p =0.44].

Conclusions: Compared with non-ticagrelor therapy, ticagrelor decreased therisk of saphenous vein graft occlusion after 1 year in patients undergoingelective CABG with saphenous vein grafting.

Disclaimer: Lupin makes no representation or warranty of any kind, expressed or implied, regarding the accuracy, adequacy, validity, reliability, availability, or completeness of any scientific information shared by the HCP on the STAR UPDATE podcast. You should not allow the contents of this to substitute for your own medical judgment, which you should exercise in evaluating the information on this website.

View Details

Clinical Efficacy and Safety of Early IntravenousAdministration of Beta-Blockers in Patients Suffering from Acute ST-Segment ElevationMyocardial Infarction without Heart Failure Undergoing Primary PercutaneousCoronary Intervention: A Study-Level Meta-Analysis of Randomized ClinicalTrials

Cardiovasc Drugs Ther. 2023 Apr 1.doi: 10.1007

Background: Several clinical studies have produced diverse results regardingthe efficacy and safety of early intravenous beta-blockers in patients withacute ST-segment elevation myocardial infarction (STEMI). A study-levelmeta-analysis of randomized clinical trials (RCTs) comparing early intravenousbeta-blockers versus placebo or routine care in STEMI patients undergoingprimary percutaneous coronary intervention (PCI) was performed.

Methods: A database search was conducted using PubMed, EMBASE, theCochrane Library, and Clinicaltrials.gov for randomized clinical trials (RCTs)that compared intravenous beta-blockers versus placebo or routine care in STEMIpatients who underwent primary PCI. The efficacy outcomes were infarct size(IS, % of LV) and the myocardial salvage index (MSI) based on magneticresonance imaging, electrocardiographic findings, heart rate, ST-segmentreduction percent (STR%), and complete STR. Safety outcomes includedarrhythmias in the first 24 h (ventricular tachycardia and fibrillation[VT/VF], atrial fibrillation [AF], bradycardia, and advanced atrioventricular[AV] block), cardiogenic shock and hypotension during hospitalization, leftventricular ejection fraction (LVEF), and major adverse cardiovascular events(cardiac death, stroke, reinfarction, and heart failure readmission) atfollow-up.

Results: Seven RCTs with 1428 patients were included in this study, with709 patients in the intravenous beta-blockers and 719 in the control group.Intravenous beta-blockers improved MSI compared to the control group (weightedmean difference [WMD] 8.46, 95% confidence interval [CI] 3.12-13.80, P = 0.002,I2 = 0%), but no differences were observed in IS (% of LV)between groups. Compared to the control group, the intravenous beta-blockersgroup had a lower risk of VT/VF (relative risk [RR] 0.65, 95% CI 0.45-0.94, P =0.02, I2 = 35%) without an increase of AF, bradycardia, andAV-block and significantly decreased HR, hypotension. LVEF at 1 week ± 7 days(WMD 2.06, 95% CI 0.25-3.88, P = 0.03, I2 = 12%) and 6 months ±7 days (WMD 3.24, 95% CI 1.54-4.95, P = 0.0002, I2 = 0%) wasimproved in the intravenous beta-blockers group compared to the control group.Subgroup analysis showed that intravenous beta-blockers before PCI decreasedthe risk of VT/VF and improved LVEF compared to the control group. Furthermore,sensitivity analysis showed that patients with a left anterior descending (LAD)artery lesion had a smaller IS (% of LV) in the intravenous beta-blockers groupcompared to the control group.

Conclusion: Intravenous beta-blockers improved the MSI, decreased the riskof VT/VF in the first 24 h, and were associated with increased LVEF at 1 weekand 6 months following PCI. In particular, intravenous beta-blockers startedbefore PCI is beneficial for patients with LAD lesions

View Details

Safe and Effective Early Use of Betablockers afterPediatric Heart Transplantationhttps://doi.org/10.1016/j.healun.2023.02.1366 Purpose: Beta-blockers (BBs) have been increasinglyincorporated into the management of heart transplant recipients, with datasupporting decreased mortality in adult recipients. However, very few studieshave evaluated the use of BBs in pediatric recipients, and early use afterpediatric heart transplantation (HTx) is still associated with hesitancy amongproviders. We sought to evaluate the safety and effectiveness of early use ofBBs after pediatric HTx.Methods:We performed a single center retrospective review ofpediatric patients (< 18 years of age) who have undergone HTx (or heartre-transplantation) from 1991 to 2022. Patients were included if they receivedany oral BBs within the first 6 months after HTx. Patients who received onlyintravenous BBs were excluded.

Results:Out of 75 HTx performed, 22 patients (29.3%) wereidentified, with 25 courses of BB therapy. Median age at HTx was 11.2 years (28days - 17.9 years). The most common indication for HTx was cardiomyopathy in17/22 cases (77.3%). BBs were most frequently started for stable atrialtachyarrhythmias in 12 cases (48%), either as monotherapy or in combinationwith other medications. Other indications included arterial hypertension orafterload reduction, ventricular arrhythmias, and diastolic heart failure. In 2patients, more than one course of BBs was given. BBs were started at a mediantime after HTx of 21 days (5-180d). Metoprolol was the most frequently used(12/25, 48%) and other agents included propranolol, carvedilol, atenolol andsotalol. Median duration of therapy was 170 days (1-1444 d). Adverse effects(symptomatic bradycardia) occurred in 2 patients; treatment had to be stoppedin 1 patient due to profound bradycardia, with full recovery afterdiscontinuation. There were no other associated complications. Earlydiscontinuation also occurred in 4 patients due to unsuccessful BB therapy(16%). At median follow-up of 4.5 years after HTx (32d - 12.3 yrs), 7 patients(31.8%) continued to receive BB therapy. There were 2 deaths (9.1%) during thisfollow-up period, both unrelated to BB effects.

View Details

Sex-stratified differences in early antithrombotictreatment response in patients presenting with ST-segment elevation myocardialinfarction

AmHeart J 2023 Apr; 258:17-26 doi: 10.1016

Background: The mechanisms underlying the increased risk of bleeding thatfemale patients with ST-segment Elevation Myocardial Infarction (STEMI)exhibit, remains unclear. The present report assessed sex-related differencesin response to pre-hospital dual antiplatelet therapy (DAPT) initiation inpatients with STEMI.

Methods: The COMPARE CRUSH trial randomized patients presenting withSTEMI to receive a pre-hospital loading dose of crushed or integral prasugreltablets in the ambulance. In this substudy, we compared platelet reactivitylevels and the occurrence of high platelet reactivity (HPR; defined as plateletreactivity ≥208) between sexes at 4 prespecified time points after DAPTinitiation, and evaluated post-PCI bleeding between groups.

Results: Out of 633 STEMI patients, 147 (23%) were female. Femalescompared with males presented with significantly higher levels of plateletreactivity and higher HPR rates at baseline (232 [IQR, 209-256] vs 195 [IQR,171-220], P < .01, and 76% vs 41%, OR 4.58 [95%CI, 2.52-8.32], P < .01,respectively). Moreover, female sex was identified as the sole independentpredictor of HPR at baseline (OR 5.67 [95%CI, 2.56-12.53], P < .01).Following DAPT initiation, levels of platelet reactivity and the incidence ofHPR were similar between sexes. Post-PCI bleeding occurred more frequently infemales compared with males (10% vs 2%, OR 6.02 [95%CI, 2.61-11.87], P <.01). Female sex was an independent predictor of post-PCI bleeding (OR 3.25[95%CI, 1.09-9.72], P = .04).

Conclusions: In this contemporary STEMI cohort, female STEMI patients remainat risk of bleeding complications after primary PCI. However, this is notexplained by sex-specific differences in the pharmacodynamic response topre-hospital DAPT initiation.

Abstract

View Details

Ticagrelor Treatment is Associated With IncreasedCoronary Flow Reserve in Survivors of Myocardial Infarctionhttps://doi.org/10.1016/j.hlc.2023.03.010AbstractBackground: The pleiotropic action of ticagrelor, with effects in addition toplatelet inhibition, has been shown to improve endothelial function in patients with coronary artery disease. These positive effects arepossibly adenosine mediated. This study investigated the association ofticagrelor therapy and coronary artery flow reserve in survivors of myocardialinfarction (MI). Methods: This was an exploratory, cross-sectional, open substudyof PROFLOW. High-risk individuals with a history of MI were identified. Coronary flow reserve (CFR) was measurednon-invasively in the left anterior descending artery using transthoracic Doppler echocardiography. Coronary flow velocity wasmeasured at rest and at maximal flow after induction of hyperaemia by intravenous infusion of adenosine at 140μg/kg/min. Patients receiving ticagrelor (n=75) were compared with those notreceiving ticagrelor (n=506), using simple and multiple linear regression models. Most patients inboth groups were treated with aspirin (97% in the ticagrelorand 94% in the non-ticagrelor group). Adjustment for traditional risk factorswas conducted. Results: The mean age at study inclusion was 68.5±6.8 years, andmost patients were male (81.8%). The simple linear regression analysis showed ticagrelortreatment to be significantly associated with increased CFR: ticagrelor2.95±0.76 (mean±SD), non-ticagrelor 2.70±0.77, (coefficient 0.25; 95% CI0.063–0.438; p=0.009). This association was significant in two of the threemultiple linear regression models with increasing numbers of variables: Model 1(0.28; 0.06–0.50; p=0.014), Model 2 (0.26; 0.03–0.48; p=0.025), and borderlinesignificant in Model 3 (0.21; –0.01 to 0.43; p=0.058). Conclusions: Ticagrelor treatment was associated withincreased CFR in this high-risk population. Increased CFR may be a clinicallyimportant therapeutic effect of ticagrelor in addition to platelet inhibition.

View Details

Sex-related bleeding risk in acute coronary syndrome patients receiving dual antiplatelet therapy with aspirin and a P2Y12 inhibitor

Med Princ Pract. 2023 Mar 22.

Abstract

Aims To study sex differences in major bleeding in relation to dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS). Methods and results The Collective Cardiology Research registry was designed to evaluate the application and outcomes of DAPT after ACS/PCI in the Rijnmond region in the Netherlands. Overall, 1172 women (median age 67.5 years) and 3087 men (62.2 years) with ACS/PCI were enrolled between August 2011 and June 2013. Based on a tailored regional DAPT guideline aiming at bleeding risk minimization, 52.6% women and 66.9% men received prasugrel as first-choice P2Y12 inhibitor, additional to aspirin. Women more frequently had contraindications for the use of prasugrel (and therefore received clopidogrel) than men (47.9 vs. 26.9%, p<0.001). Femoral access was more common in women than in men (47.6 vs. 38.1%, p<0.001). Women had higher incidence of TIMI major bleeding at 1 year than men (2.6 vs. 1.6%, p=0.018). After adjustment for established bleeding risk factors, female sex was associated with over two-fold higher risk of TIMI major bleeding (adjusted hazard ratio 2.33; 95% confidence interval 1.26 to 4.32). This difference was already apparent at discharge, and appeared to be caused by access site bleedings (0.9 vs. 0.1%, p<0.001). No sex differences were found in non-access site related TIMI major bleeding up to 1 year. Conclusion Women with ACS/PCI receiving DAPT had higher TIMI major bleeding risk caused by an excess in access-site bleeds, mainly in relation to the femoral approach.

Disclaimer: Lupin makes no representation or warranty of any kind, expressed or implied, regarding the accuracy, adequacy, validity, reliability, availability, or completeness of any scientific information shared by the HCP on the ¬¬¬STAR UPDATE podcast. You should not allow the contents of this to substitute for your own medical judgment, which you should exercise in evaluating the information on this website.

View Details

Effect of early metoprolol before PCI in ST-segment elevation myocardial infarction on infarct size and left ventricular ejection fraction. A systematic review and meta-analysis of clinical trials

Clin Cardiol. 2022 Oct;45(10):1011-1028.

Abstract

Aim: This meta-analysis aims to look at the impact of early intravenous Metoprolol in ST-segment elevation myocardial infarction (STEMI) before percutaneous coronary intervention (PCI) on infarct size, as measured by cardio magnetic resonance (CMR) and left ventricular ejection fraction.

Methods: We searched the following databases: PubMed, Scopus, Cochrane library, and Web of Science. We included only randomized control trials that reported the use of early intravenous Metoprolol in STEMI before PCI on infarct size, as measured by CMR and left ventricular ejection fraction. RevMan software 5.4 was used for performing the analysis.

Results: Following a literature search, 340 publications were found. Finally, 18 studies were included for the systematic review, and 8 clinical trials were included in the meta-analysis after the full-text screening. At 6 months, the pooled effect revealed a statistically significant association between Metoprolol and increased left ventricular ejection fraction (LVEF) (%) compared to controls (mean difference [MD] = 3.57, [95% confidence interval [CI] = 2.22-4.92], p < .00001), as well as decreased infarcted myocardium(g) compared to controls (MD = -3.84, [95% [CI] = -5.75 to -1.93], p < .0001). At 1 week, the pooled effect revealed a statistically significant association between Metoprolol and increased LVEF (%) compared to controls (MD = 2.98, [95% CI = 1.26-4.69], p = .0007), as well as decreased infarcted myocardium(%) compared to controls (MD = -3.21, [95% CI = -5.24 to -1.18], p = .002).

Conclusion: A significant decrease in myocardial infarction and increase in LVEF (%) was linked to receiving Metoprolol at 1 week and 6-month follow-up.

Disclaimer: Lupin makes no representation or warranty of any kind, expressed or implied, regarding the accuracy, adequacy, validity, reliability, availability, or completeness of any scientific information shared by the HCP on the ¬¬¬STAR UPDATE podcast. You should not allow the contents of this to substitute for your own medical judgment, which you should exercise in evaluating the information on this website.

View Details

Beta-Blockers for Primary Prevention of Anthracycline-Induced Cardiac Toxicity: An Updated Meta-Analysis of Randomized Clinical Trials

Cardiovasc Ther. 2022 Dec 29;2022:8367444.

Abstract

Aim: Cardiotoxicity is a well-recognized complication of chemotherapy with Anthracyclines. However, results from trials evaluating beta-blockers for prevention are controversial. Therefore, we performed a meta-analysis to find whether prophylactic administration of beta-blockers can help prevent Anthracyclines-induced cardiotoxicity.

Methods: We assessed randomized trials and observational studies where a prophylactic intervention was compared with a control arm in patients with a normal left ventricular ejection fraction (LVEF) receiving Anthracyclines. The primary outcome was EF reduction. The secondary outcome was the development of Cancer Therapeutics-Related Cardiac Dysfunction (CTRCD), defined as a decrease in the LVEF of >10% to a value of <53%.

Results: We included 17 trials comprising 1291 patients (671 patients in the intervention arm and 620 in the control arm). Carvedilol was administered in eight studies, and others used bisoprolol, metoprolol, or nebivolol. Compared with baseline, LVEF reduced in both intervention and control groups after chemotherapy (MD = -1.93%, 95% CI: -2.94, -0.92, p = 0.001, I2 = 72.1% vs. MD = -4.78%, 95% CI: -6.51, -3.04, p = 0.001, I 2 = 91.6%, respectively). LVEF was less reduced among the beta-blocker receivers (MD = 3.44%, 95% CI: 1.41-5.46, p = 0.001, I2 = 94.0%). Among the eight studies reporting the incidence of CTRCD, 45 out of 370 participants in the intervention arm and 54 out of 341 in the control arm were reported to experience this complication (RR = 0.76; 95% CI: 0.53,1.09; I 2 = 24.4%; p = 0.235).

Conclusion: Treatment with beta-blockers prevents dilatation of the left ventricle, development of diastolic dysfunction, and reduction of LVEF. However, these hemodynamic effects do not translate into a significant reduction in CTRCD incidence and prevention of hospitalization for heart failure or cardiac death.

Disclaimer: Lupin makes no representation or warranty of any kind, expressed or implied, regarding the accuracy, adequacy, validity, reliability, availability, or completeness of any scientific information shared by the HCP on the ¬¬¬STAR UPDATE podcast. You should not allow the contents of this to substitute for your own medical judgment, which you should exercise in evaluating the information on this website.

View Details

Can platelet count be controlled with ticagrelor in patients with essential thrombocythaemia? A case series

Eur Heart J Case Rep. 2023 Feb 14;7(2):ytad051

Abstract

Background: Essential thrombocythaemia (ET) is defined as a myeloproliferative neoplasm with a tendency to haemorrhage and thrombosis. Acute coronary thrombosis can be observed in 1 out of 10 patients. The management of ET patients with acute coronary syndrome (ACS) is a complex clinical condition that requires close follow-up.

Case summary: Case-1: a 52-year-old female patient with a diagnosis of ET with Janus kinase (JAK)--2 mutation, despite using cytoreductive agents, platelet counts could not be controlled. Platelet counts started to follow a normal course with the ticagrelor treatment given after ACS. Case-2: a 49-year-old female patient who was given ticagrelor treatment after ACS was found to have JAK-2+ ET. The patient whose platelet count returned to normal after ticagrelor treatment was using a cytoreductive agent before the index event. Case-3: a 54-year-old female patient with ET without any genetic mutation. In the patient whose platelet count did not decrease despite ticagrelor treatment and cytoreductive agents given after ACS, platelet counts returned to normal with interferon therapy.

Discussion: Platelet counts returned to the normal range with ticagrelor treatment given after ACS in patients with JAK+ ET. Monitoring platelet reduction in JAK+ patients with P2Y12 inhibition is thought to be important for new treatment options.

Disclaimer: Lupin makes no representation or warranty of any kind, expressed or implied, regarding the accuracy, adequacy, validity, reliability, availability, or completeness of any scientific information shared by the HCP on the STAR UPDATE podcast. You should not allow the contents of this to substitute for your own medical judgment, which you should exercise in evaluating the information on this website.

View Details

Interventional therapy of acute coronary syndromes in very old patient population and results of 2 years follow-up

Egypt Heart J. 2023 Feb 22;75(1):14. doi: 10.1186/s43044-023-00340-x.

Abstract

Background:Research on cardiovascular treatment options and prognosis in very old age groups of patients is warranted. In our study, we evaluated and followed up on clinical conditions on admission and comorbidities of patients older than 80 years who were admitted to our hospital with acute myocardial infarction and shared our findings.

Results:A total of 144 patients were included in the study, with a mean age of 84.56 ± 5.01 years. No complications resulting in death or requiring surgery were observed in the patients. All-cause mortality was found to be related to heart failure, chronic pulmonary disease shock, and C-reactive protein levels. Cardiovascular mortality was correlated to heart failure, shock on admission, and C-reactive protein levels. No significant difference in mortality was observed between Non-ST elevated myocardial infarction and ST-elevation myocardial infarction.

Conclusions:Percutaneous coronary intervention is a safe treatment option with low complication and mortality rates in very old patients with acute coronary syndromes.

Disclaimer: Lupin makes no representation or warranty of any kind, expressed or implied, regarding the accuracy, adequacy, validity, reliability, availability, or completeness of any scientific information shared by the HCP on the STAR UPDATE podcast. You should not allow the contents of this to substitute for your own medical judgment, which you should exercise in evaluating the information on this website.

View Details

Blood pressure lowering effects of β-blockers as add-on or combination therapy: A meta-analysis of randomized controlled trials

J Clin Hypertens (Greenwich). 2023 Feb 8. doi: 10.1111/jch.14616. Online ahead of print.

Abstract:

The authors performed a meta-analysis to assess the efficacy of non-atenolol β-blockers as add-on to monotherapy or as a component of combination antihypertensive therapy in patients with hypertension. The authors searched and identified relevant randomized controlled trials from PubMed until November 2021. Studies comparing blood pressure lowering effects of β-blockers with diuretics, calcium channel blockers (CCBs), angiotensin-converting enzyme inhibitors (ACEIs), or angiotensin receptor blockers (ARBs) were included. The analysis included 20 studies with 5544 participants. β-blockers add-on to monotherapy significantly reduced systolic and diastolic blood pressure as compared with non-β-blocker monotherapy (weighted mean difference in mm Hg [95% confidence interval]: -4.1 [-6.0, -2.2] and -3.7 [-4.6, -2.8], respectively). These results were consistent across the comparisons with diuretics (systolic pressure, -10.2 [-14.2, -6.2]; diastolic pressure, -5.4 [-8.2, -2.6]), CCBs (systolic pressure, -4.1 [-7.1, -1.0]; diastolic pressure, -2.8 [-4.1, -1.5]), and ACEIs/ARBs (systolic pressure, -2.9 [-4.3, -1.5]; diastolic pressure, -4.2 [-5.0, -3.4]). There was no significant difference in blood pressure lowering effects between combinations with and without a β-blocker (systolic pressure, -1.3 mm Hg [-5.8, 3.2]; diastolic pressure, -.3 mm Hg [-2.7, 2.1]). Metoprolol add-on or combination therapy had a significantly greater blood pressure reduction than non-β-blocker therapy (systolic pressure, -3.6 mm Hg [-5.9, -1.3]; diastolic pressure, -2.1 mm Hg [-3.5, -.7]). In conclusion, non-atenolol β-blockers are effective in lowering blood pressure as add-on to monotherapy or as a component of combination antihypertensive therapy. In line with the current hypertension guideline recommendations, β-blockers can and should be used in combination with other antihypertensive drugs.

Disclaimer: Lupin makes no representation or warranty of any kind, expressed or implied, regarding the accuracy, adequacy, validity, reliability, availability, or completeness of any scientific information shared by the HCP on the STAR UPDATE podcast. You should not allow the contents of this to substitute for your own medical judgment, which you should exercise in evaluating the information on this website.

View Details

A predictive model of response to metoprolol in children and adolescents with postural tachycardia syndrome

World J Pediatr. 2023 Feb 13. doi: 10.1007/s12519-022-00677-4. Online ahead of print.

Abstract

Background:The present work was designed to explore whether electrocardiogram (ECG) index-based models could predict the effectiveness of metoprolol therapy in pediatric patients with postural tachycardia syndrome (POTS).

Methods:This study consisted of a training set and an external validation set. Children and adolescents with POTS who were given metoprolol treatment were enrolled, and after follow-up, they were grouped into non-responders and responders depending on the efficacy of metoprolol. The difference in pre-treatment baseline ECG indicators was analyzed between the two groups in the training set. Binary logistic regression analysis was further conducted on the association between significantly different baseline variables and therapeutic efficacy. Nomogram models were established to predict therapeutic response to metoprolol. The receiver-operating characteristic curve (ROC), calibration, and internal validation were used to evaluate the prediction model. The predictive ability of the model was validated in the external validation set.

Results:Of the 95 enrolled patients, 65 responded to metoprolol treatment, and 30 failed to respond. In the responders, the maximum value of the P wave after correction (Pcmax), P wave dispersion (Pd), Pd after correction (Pcd), QT interval dispersion (QTd), QTd after correction (QTcd), maximum T-peak-to-T-end interval (Tpemax), and T-peak-to-T-end interval dispersion (Tped) were prolonged (all P < 0.01), and the P wave amplitude was increased (P < 0.05) compared with those of the non-responders. In contrast, the minimum value of the P wave duration after correction (Pcmin), the minimum value of the QT interval after correction (QTcmin), and the minimum T-peak-to-T-end interval (Tpemin) in the responders were shorter (P < 0.01, < 0.01 and < 0.01, respectively) than those in the non-responders. The above indicators were screened based on the clinical significance and multicollinearity analysis to construct a binary logistic regression. As a result, pre-treatment Pcmax, QTcmin, and Tped were identified as significantly associated factors that could be combined to provide an accurate prediction of the therapeutic response to metoprolol among the study subjects, yielding good discrimination [area under curve (AUC) = 0.970, 95% confidence interval (CI) 0.942-0.998] with a predictive sensitivity of 93.8%, specificity of 90.0%, good calibration, and corrected C-index of 0.961. In addition, the calibration curve and standard curve had a good fit. The accuracy of internal validation with bootstrap repeated sampling was 0.902. In contrast, the kappa value was 0.769, indicating satisfactory agreement between the predictive model and the results from the actual observations. In the external validation set, the AUC for the prediction model was 0.895, and the sensitivity and specificity were 90.9% and 95.0%, respectively.

Conclusions: A high-precision predictive model was successfully developed and externally validated. It had an excellent predictive value of the therapeutic effect of metoprolol on POTS among children and adolescents.

Disclaimer: Lupin makes no representation or warranty of any kind, expressed or implied, regarding the accuracy, adequacy, validity, reliability, availability, or completeness of any scientific information shared by the HCP on the STAR UPDATE podcast. You should not allow the contents of this to substitute for your own medical judgment, which you should exercise in evaluating the information on this website.

View Details

Ticagrelor With or Without Aspirin in High-Risk Patients With Anemia Undergoing Percutaneous Coronary Intervention: a subgroup analysis of the TWILIGHT trial

Eur Heart J Cardiovasc Pharmacother. 2023 Jan 17;pvad006.

Abstract

Aim: The aim of this study was to assess the effect of ticagrelor monotherapy among high-risk patients with anemia undergoing percutaneous coronary intervention (PCI).

Methods and results:In the TWILIGHT trial (Ticagrelor With Aspirin or Alone in High-Risk Patients after Coronary Intervention), after 3 months of ticagrelor plus aspirin, high-risk patients were maintained on ticagrelor and randomized to aspirin or placebo for 1 year. Anemia was defined as hemoglobin <13 g/dL for men and <12 g/dL for women. The primary endpoint was Bleeding Academic Research Consortium (BARC) 2, 3, or 5 bleeding. The key secondary endpoint was a composite of all-cause death, myocardial infarction, or stroke.Out of 6 828 patients, 1 329 (19.5%) had anemia and were more likely to have comorbidities, multivessel disease, and to experience bleeding or ischemic complications than non-anemic patients. Among anemic patients, BARC 2, 3, or 5 bleeding occurred less frequently with ticagrelor monotherapy than with ticagrelor plus aspirin (6.4% vs. 10.7%; HR 0.60; 95% CI 0.41 to 0.88; p = 0.009); the rate of the key secondary endpoint was similar in the two arms (5.2% vs. 4.8%; HR 1.07; 95% CI 0.66 to 1.74; p = 0.779). These effects were consistent in patients without anemia (interaction p-value 0.671 and 0.835, respectively).

Conclusions:In high-risk patients undergoing PCI, ticagrelor monotherapy after 3 months of ticagrelor-based DAPT was associated with a reduced risk of clinically relevant bleeding without any increase in ischemic events irrespective of anemia status.

Disclaimer: Lupin makes no representation or warranty of any kind, expressed or implied, regarding the accuracy, adequacy, validity, reliability, availability, or completeness of any scientific information shared by the HCP on the STAR UPDATE podcast. You should not allow the contents of this to substitute for your own medical judgment, which you should exercise in evaluating the information on this website.

View Details

Stroke Recurrence and Antiplatelets in Posterior Versus Anterior Circulation Minor Stroke or Transient Ischemic Attack

Stroke. 2023 Feb 15. doi: 10.1161/STROKEAHA.122.041738.

Abstract

Background:It is unclear whether infarct location affects stroke recurrence after index ischemic stroke. We aimed to compare the risk of stroke recurrence and the responses to dual antiplatelets with ticagrelor-aspirin versus clopidogrel-aspirin between patients with posterior circulation infarct (PCI) and those with anterior circulation infarct (ACI) after minor stroke or transient ischemic attack.

Methods:Data were obtained from the double-blind CHANCE-2 trial (Ticagrelor or Clopidogrel With Aspirin in High-Risk Patients With Acute Nondisabling Cerebrovascular Events II), which was conducted across 202 centers in China from September 2019 to March 2021. Patients with positive diffusion-weighted imaging were included and classified into PCI and ACI groups according to the hyperintense lesions on diffusion-weighted imaging. The primary efficacy and safety outcomes were a new stroke and severe or moderate bleeding within 90 days, respectively.

Results: A total of 4168 patients were included in this substudy, with 1427 PCI and 2741 ACI. During the 90-day follow-up, the risk of stroke recurrence in patients with PCI was similar to that with ACI (7.4% versus 8.3%; adjusted hazard ratio, 1.01 [95% CI, 0.79-1.29]; P=0.94). In comparison with clopidogrel-aspirin, ticagrelor-aspirin significantly reduced the risk of stroke recurrence in both the PCI (hazard ratio, 0.59 [95% CI, 0.40-0.89]; P=0.01) and ACI groups (hazard ratio, 0.65 [95% CI, 0.50-0.85]; P=0.002). There was no treatment-by-infarct location interaction (P value for interaction, 0.92). The risk of severe or moderate bleeding was similar between PCI and ACI patients (P=0.19). However, the risk of any bleeding increased on ticagrelor-aspirin than clopidogrel-aspirin treatment in PCI and ACI patients (P=0.02 and 0.002, respectively).

Conclusions:Our study demonstrated that stroke recurrence was similar between PCI and ACI in patients with minor stroke or transient ischemic attack. Additionally, ticagrelor-aspirin was superior to clopidogrel-aspirin in reducing the risk of stroke within 90 days in both PCI and ACI patients.

Disclaimer: Lupin makes no representation or warranty of any kind, expressed or implied, regarding the accuracy, adequacy, validity, reliability, availability, or completeness of any scientific information shared by the HCP on the STAR UPDATE podcast. You should not allow the contents of this to substitute for your own medical judgment, which you should exercise in evaluating the information on this website.

View Details

Abstract

Background: Academic Research Consortium for High Bleeding Risk (ARC-HBR) criteria have been used to identify high-risk patients undergoing percutaneous coronary intervention (PCI) in current clinical practice. This study aimed to evaluate the association between the number of ARC-HBR criteria and clinical outcomes in patients with acute coronary syndrome (ACS) after an emergent PCI.

Methods: We assessed 338 consecutive patients with ACS who underwent successful emergent PCI between January 2017 and December 2020. The ARC-HBR score was calculated by assigning 1 point to each major criterion and 0.5 points to each minor criterion. The patients were classified into low (ARC-HBR score < 1), intermediate (1 ≤ ARC-HBR score < 2), and high (ARC-HBR score ≥ 2) bleeding risk groups. We investigated the association between the ARC-HBR score and major adverse cardiovascular events (MACEs), defined as a composite of all-cause death, non-fatal myocardial infarction, and non-fatal stroke. We also compared the diagnostic ability of the ARC-HBR score and Controlled Abciximab and Device Investigation and Lower Late Angiography Complications (CADILLAC) risk score.

Results: The mean age of the patients was 67.6 ± 12.4 years, and 78.4 % were men. During the median follow-up of 864 (557-1309) days, 70 patients developed MACEs. Kaplan-Meier curves showed that the cumulative incidence of MACE was significantly higher as the ARC-HBR score increased in a stepwise manner (log-rank p < 0.001). There were no significant differences in the area under the receiver operating characteristic curve (AUC) for predicting MACE within two years after an emergent PCI between the ARC-HBR and CADILLAC risk scores (AUC: 0.763 vs. 0.777).

Conclusions: ARC-HBR score was independently associated with an increased risk of MACE in patients with ACS after an emergent PCI. Moreover, it had a similar diagnostic ability for predicting MACE within two years compared to the CADILLAC risk score.

Disclaimer: Lupin makes no representation or warranty of any kind, expressed or implied, regarding the accuracy, adequacy, validity, reliability, availability, or completeness of any scientific information shared by the HCP on the STAR UPDATE podcast. You should not allow the contents of this to substitute for your own medical judgment, which you should exercise in evaluating the information on this website.

View Details

Abstract

β-blockers have been widely utilized as a part of acute myocardial infarction (AMI) treatment for the past 40 years. Patients receiving β-adrenergic blockers for an extended period following myocardial infarction have a higher chance of surviving. Although many patients benefited from β-blockers, many do not, including those with myocardial infarction, left ventricle dysfunction, chronic pulmonary disease, and elderly people. In individuals with post-acute coronary syndrome and normal left ventricular ejection fraction (LVEF), the appropriate duration of beta-blocker therapy is still unknown. There is also no time limit for those without cardiac angina and who do not need β-blockers for dysrhythmia or hypertension. Interestingly, β-blockers have been prescribed for more than four decades. The novel mechanism of action on cellular compartments has been found continually, which opens a new way for their potential application in cardiac failure and other cardiac events like post-myocardial infarction. Here, in this review, we studied β-blocker usage in these circumstances and the current recommendations for β-blocker use from clinical practice guidelines.

Disclaimer: Lupin makes no representation or warranty of any kind, expressed or implied, regarding the accuracy, adequacy, validity, reliability, availability, or completeness of any scientific information shared by the HCP on the STAR UPDATE podcast. You should not allow the contents of this to substitute for your own medical judgment, which you should exercise in evaluating the information on this website.

View Details

Abstract

Objective: To determine if the baseline baroreflex sensitivity (BRS) could be a useful predictor for the metoprolol therapeutic efficacy on postural orthostatic tachycardia syndrome (POTS) in children.

Methods: In this retrospective case-control study, 54 children suffering from POTS treated with metoprolol were recruited from the pediatric department of Peking University First Hospital. After 2-3 months of metoprolol treatment, all subjects were divided into responders and non-responders based on whether the symptom score (SS) was decreased by over 50% after metoprolol treatment at the follow-up. The baseline demographic parameters and the supine BRS during the head-up tilt test (HUTT) obtained by Finapres Medical System (FMS) were compared between the two groups. The value of BRS to predict the effectiveness of POTS was analyzed by a receiver-operating characteristic (ROC) curve.

Results: The age, sex, height, weight, body mass index (BMI), course of the disease, baseline SS, medication time, metoprolol dose, and follow-up time of the subjects were not statistically different between the responders and non-responders (P > 0.05). The decline in symptom scores (ΔSS) of the responders was more obvious than that of the non-responders (P < 0.01). The supine BRS, BRS at maximum HR, supine heart rate (HR), and maximum HR were different between responders and non-responders (P < 0.01, P = 0.022, P < 0.01, P = 0.047). The binary multivariable analysis showed that baseline supine BRS was significantly associated with the response to metoprolol therapy [OR: 2.079, 95% CI: (1.077, 4.015), P = 0.029]. According to the ROC curve, the area under the curve (AUC) of baseline BRS was 0.912 (95% CI, 0.840-0.984), with a cut-off value of 8.045 ms/mmHg, yielding a sensitivity and specificity of 75.8% and 95.2%, respectively, in predicting the effectiveness of POTS.

Conclusion: The baseline supine BRS level > 8.045 ms/mmHg can predict a good therapeutic response to metoprolol and the results would assist in guiding the individualized β-adrenoceptor blocker use in pediatric patients suffering from POTS.

Disclaimer: Lupin makes no representation or warranty of any kind, expressed or implied, regarding the accuracy, adequacy, validity, reliability, availability, or completeness of any scientific information shared by the HCP on the STAR UPDATE podcast. You should not allow the contents of this to substitute for your own medical judgment, which you should exercise in evaluating the information on this website.

View Details

Abstract

Background: No study has compared pharmacologic properties of ticagrelor and clopidogrel in non-dialysis patients with stage 4-5 chronic kidney disease (CKD).

Methods: We conducted a double-blind RCT to compare effects of ticagrelor and clopidogrel in 48 CKD, with the primary outcome of ADP-induced platelet aggregation (WBPA) after 2 weeks of DAPT. In a parallel arm, we compared effects of 2 weeks of ticagrelor plus aspirin on mean changes in WBPA and markers of thromboinflammation among non-CKD controls (n = 26) with that of CKD in the ticagrelor-arm.

Results: Average age of CKD was 53.7 years, with 62% women, 54% African American, and 42% with stage 5 CKD. Ticagrelor generated statistically lower WBPA values post treatment [median 0 Ω (IQR 0, 2)] vs. clopidogrel [median 0 Ω (IQR 0, 5)] (P = 0.002); percent inhibition of WBPA was greater (87 ± 22% vs. 63 ± 50%; P = 0.04; and plasma IL-6 levels were much lower (8.42 ± 1.73 pg/ml vs. 18.48 ± 26.56 pg/ml; P = 0.04). No differences in mean changes in WBPA between CKD-ticagrelor and control groups were observed. Ticagrelor- DAPT reduced levels of IL-1α and IL-1β in CKD-ticagrelor and control groups, attenuated lowering of TNFα and TRAIL levels in CKD-ticagrelor (vs controls), and had global changes in correlation between various cytokines in a subgroup of CKD-ticagrelor subjects not on statins (n = 10). Peak/trough levels of ticagrelor/metabolite were not different between CKD-ticagrelor and control groups.

Conclusions: We report significant differences in platelet aggregation and anti-inflammatory properties between ticagrelor- and clopidogrel-based DAPT in non-dialysis people with stage 4-5 CKD. These notable inflammatory responses suggest ticagrelor-based DAPT might lower inflammatory burden of asymptomatic patients with stage 4 or 5 CKD.

Disclaimer: Lupin makes no representation or warranty of any kind, expressed or implied, regarding the accuracy, adequacy, validity, reliability, availability, or completeness of any scientific information shared by the HCP on the STAR UPDATE podcast. You should not allow the contents of this to substitute for your own medical judgment, which you should exercise in evaluating the information on this website.

View Details

The prognostic effect of ST-elevation in lead aVR on coronary artery disease, and outcome in acute coronary syndrome patients: a systematic review and meta-analysis

Eur J Med Res. 2022 Dec 21;27(1):302.

Abstract

Background: Rapid diagnosis of coronary artery disease has an important role in saving patients. The aim of this study is to evaluate if aVR lead ST-elevation (STE) can predict LM/3VD, left main (LM) disease, and three-vessel disease (3VD), outcome in acute coronary syndrome (ACS) patients.

Methods: In this systematic review and meta-analysis, 45 qualified studies were entered. Scopus, Pub med, Google scholar, Web of science, Cochrane library were searched on 12 November 2021.

Results: This systematic review includes 52,175 participants. In patients with STE, the total odds ratios for LM, 3VD, and LM/3VD were 5.48 (95% CI 3.88, 7.76), 2.21 (95% CI 1.78, 3.27), and 6.21 (95% CI 3.49, 11,6), respectively. STE in lead aVR was linked with in-hospital death (OR = 2.99, CI 1.90, 4.72) and 90-day mortality (OR = 3.09, CI 2.17, 4.39), despite the fact that it could not predict 30-day mortality (OR = 1.11, CI 0.95, 1.31). The STE > 1 mm subgroup had the highest sensitivity for LM (0.9, 95% CI 0.82, 0.98), whereas the STE > 0.5 mm (0.76, 95% CI 0.61, 0.90) subgroup had the highest sensitivity for LM/3VD. The appropriate cut-off point with highest specificity for LM/3VD and LM was STE > 1.5 mm (0.80, 95% CI 0.75, 0.85) and STE > 0.5 mm, respectively (0.75, 95% CI 0.67, 0.84, I2 = 97%).

Conclusion: The odds of LM and LM/3VD were higher than 3VD in ACS patients with STE in lead aVR. Also, STE > 0.5 mm was the best cut-off point to screen LM/3VD, whereas for LM diagnosis, STE > 1 mm had the highest sensitivity. Furthermore, LM/3VD had a higher overall specificity than LM.

Disclaimer: Lupin makes no representation or warranty of any kind, expressed or implied, regarding the accuracy, adequacy, validity, reliability, availability, or completeness of any scientific information shared by the HCP on the STAR UPDATE podcast. You should not allow the contents of this to substitute for your own medical judgment, which you should exercise in evaluating the information on this website.

View Details

Cardio-selective versus non-selective β-blockers for cardiovascular events and mortality in long-term dialysis patients: A systematic review and meta-analysis

PLoS One. 2022 Dec 19;17(12):e0279171.

Abstract

Background: Trials in patients receiving dialysis have demonstrated that β-blockers reduce all-cause mortality and cardiovascular events. However, differences still exist within-class comparative effectiveness studies of the therapeutic benefits of β-blockers in dialysis patients.

Objective: The purpose of this systematic review is to examine whether cardiovascular events and all-cause mortality differed between dialysis patients receiving cardio-selective and non-selective agents.

Methods: A comprehensive search of relevant articles from the PubMed, EMBASE, Cochrane Central Register and ClinicalTrials.gov was performed up to September 4, 2022, we included adults receiving β-blockers to evaluate the effects of cardio-selective versus non-selective agents on mortality and cardiovascular events in the dialysis population. Hazard ratios (HRs) and 95% confidence intervals (CIs) were examined for the negative outcomes of cardiovascular events and death for any reason. The risk of bias in randomized controlled trials (RCTs) was assessed using Cochrane's risk of bias tool and the risk of bias in observational studies was assessed using a table designed according to the ROBINS-I tool, the evidence grade was assessed using the GRADE guideline. For all-cause mortality and cardiovascular events, the RevMan software (version 5.3) was used to calculate pooled HRs with 95% CI. The heterogeneity (I2) in statistics was used to examine the degree of heterogeneity among studies.

Results: Four observational studies, including 58, 652 long-term dialysis patients, were included in the meta-analysis. Compared to dialysis patients who took non-selective β-blockers, who took cardio-selective β-blockers was probably associated with fewer cardiovascular events (hazard ratio [HR] = 0.85, 95% confidence interval [CI] = 0.81, 0.89, heterogeneity [I2] = 0%, three trials, 52,077 participants, moderate-quality evidence) andmay have lower all-cause mortality (HR = 0.83, 95% CI = 0.69, 0.99, I2 = 91%, four trials, 54,115 participants, low-quality evidence).

Conclusions: This systematic review showed that cardio-selective β-blockers are probably associated with fewer cardiovascular events and may have lower all-cause mortality in long-term dialysis patients than non-selective β-blockers. The present study results need to be replicated using randomized controlled trials with longer observation durations.

Disclaimer: Lupin makes no representation or warranty of any kind, expressed or implied, regarding the accuracy, adequacy, validity, reliability, availability, or completeness of any scientific information shared by the HCP on the STAR UPDATE podcast. You should not allow the contents of this to substitute for your own medical judgment, which you should exercise in evaluating the information on this website.

View Details

Efficacy of metoprolol plus atorvastatin for carotid atherosclerosis and its influence on carotid intima-media thickness and homocysteine level

Abstract

Objective: To analyze the effects of metoprolol (MET) plus atorvastatin (ATO) on carotid intima-media thickness (IMT) and homocysteine (Hcy) level in carotid atherosclerosis (CAS) patients.

Methods: In this retrospective study, 90 patients with CAS admitted to the Hangzhou Ninth People's Hospital between January 2019 and July 2021 were enrolled, including 40 cases (control group, the Con) treated with MET and 50 cases treated with the combination therapy of MET plus ATO (Research group, the Res). The efficacy and related influencing factors were observed and compared. The clinical effects (IMT, plaque score), Hcy level, inflammatory cytokines (ICs; matrix metalloproteinase-9 [MMP-9], high-sensitivity C-reactive protein [hs-CRP]), blood lipid indices (low-/high- density lipoprotein cholesterol [LDL-C/HDL-C], total cholesterol [TC], triglyceride [TG]) and coagulation markers (thrombin time [TT], prothrombin time [PT], activated partial thromboplastin time [APTT], fibrinogen [FIB]) of the two groups were observed and compared.

Results: The results identified a statistically higher overall response rate in the Res group. Age, coronary heart disease, cerebral infarction and plaque score were confirmed to be closely related to the efficacy of CAS. In addition, statistically lower post-treatment IMT, plaque score, MMP-9, hs-CRP, LDL-C, TG, TC and FIB while higher PT, TT and APTT were determined in the Res group compared with the pre-treatment values and the Con group.

Conclusions: MET plus ATO can significantly improve efficacy, reduce IMT and plaque score of patients with CAS, as well as improve inflammatory factors, blood lipid indices and coagulation markers, for which it deserves clinical promotion.

Disclaimer: Lupin makes no representation or warranty of any kind, expressed or implied, regarding the accuracy, adequacy, validity, reliability, availability, or completeness of any scientific information shared by the HCP on the STAR UPDATE podcast. You should not allow the contents of this to substitute for your own medical judgment, which you should exercise in evaluating the information on this website.

View Details

Treatment of the New Era: Long-Term Ticagrelor Monotherapy for the Treatment of Patients with Type 2 Diabetes Mellitus following Percutaneous Coronary Intervention: A Meta-analysis

Abstract:

Introduction: Type 2 diabetes mellitus (T2DM) is a risk factor for the development of coronary artery disease (CAD). In patients with acute coronary syndrome (ACS), guidelines recommend a potent P2Y12 inhibitor in addition to aspirin. For those with complicated and advanced CAD requiring complex percutaneous coronary intervention (PCI), the risk for adverse ischemic events is even higher. Prolonged dual antiplatelet therapy (DAPT) use is controversial. A new antiplatelet regimen after PCI should be considered. In this analysis, we aimed to systematically show the impact of long-term ticagrelor monotherapy after a short course of DAPT use on the outcomes in patients with T2DM following PCI.

Methods: Electronic databases were searched for relevant publications. Studies that were based on patients with T2DM and that included patients with T2DM were selected on the basis of the inclusion and exclusion criteria. Statistical analysis was carried out with RevMan software. The data are presented as risk ratios (RR) with 95% confidence intervals (CI).

Results: A total of 8621 patients were included in this analysis, whereby 4357 participants with T2DM were assigned to ticagrelor monotherapy and 4264 were assigned to DAPT. Our results showed long-term ticagrelor monotherapy after a short course of DAPT use to be associated with a significantly lower risk of major adverse cardiac events (RR 0.86, 95% CI 0.77-0.98; P = 0.02) and all-cause mortality (RR 0.77, 95% CI 0.60-0.98; P = 0.03). However, no significant difference was observed in cardiac death, myocardial infarction, stroke, stent thrombosis, or repeated revascularization. Ticagrelor monotherapy was associated with significantly lower risk of thrombolysis in myocardial infarction (TIMI) defined minor or major bleeding (RR 0.71, 95% CI 0.54-0.93; P = 0.01) compared with the DAPT regimen.

Conclusion: Long-term ticagrelor monotherapy after a short course of DAPT use showed better results in patients with T2DM following PCI. Therefore, ticagrelor monotherapy after a short course of DAPT use could be considered an evolution in antiplatelet therapy of this decade for the treatment of patients with T2DM after PCI. However, newer studies with a larger population size and cost-effectiveness are factors that should further be considered.

Disclaimer: Lupin makes no representation or warranty of any kind, expressed or implied, regarding the accuracy, adequacy, validity, reliability, availability, or completeness of any scientific information shared by the HCP on the STAR UPDATE podcast. You should not allow the contents of this to substitute for your own medical judgment, which you should exercise in evaluating the information on this website.

View Details

Abstract

Background: This study aimed to investigate associations of serum high-sensitivity C-reactive protein (hsCRP) and social support (SS) levels with suicidal ideation (SI), and to evaluate potential modifying effects of SS on the associations between serum hsCRP levels and SI in two longitudinal cohorts with cardio-/cerebrovascular diseases.

Methods: 1152 acute coronary syndrome (ACS) and 423 stroke patients were recruited at baseline within 2 weeks of disease onset, and evaluated for: i) serum hsCRP levels; ii) SS by the Social Support Scale and Social Undermining Scale; iii) SI by the "suicidal thoughts" item of the Montgomery-Åsberg Depression Rating Scale; and iv) covariates including socio-demographics, depression, vascular risk factors, and index disease severity. At 12-month follow-up, SI was re-evaluated. Logistic regression models were used to adjust for potential covariates.

Results: In the ACS cohort, higher serum hsCRP and lower SS levels were significantly associated with SI at baseline; and only lower SS levels were significantly associated with SI at follow-up. In the stroke cohort, lower SS levels were significantly associated with SI at baseline; but no other association was found. Associations of serum hsCRP levels with SI at both baseline and follow-up were only significant at higher SS levels with significant interaction terms in both cohorts.

Conclusions: By considering SS evaluations with routine serum hsCRP levels in cardio-/cerebrovascular disease, clinical prediction of SI both at acute and chronic phases of the diseases might be improved.

Disclaimer: Lupin makes no representation or warranty of any kind, expressed or implied, regarding the accuracy, adequacy, validity, reliability, availability, or completeness of any scientific information shared by the HCP on the STAR UPDATE podcast. You should not allow the contents of this to substitute for your own medical judgment, which you should exercise in evaluating the information on this website.

View Details

Abstract

Background: Atrial fibrillation (AF) is the most prevalent cardiac arrhythmia. Previous studies showed that rhythm and rate control strategies are associated with similar rates of mortality and serious morbidity. Beta blockers (BB) and calcium channel blockers (CCB) are commonly used and the selection between these two medications depends on personal preference.

Objectives: To compare real-time capability of BB and CCB for the treatment of rapid AF and to estimate their efficacy in reducing hospitalization duration.

Methods: We conducted a retrospective cohort study of 306 patients hospitalized at Soroka Hospital during a 5-year period with new onset AF who were treated by a rate control strategy.

Results: A significant difference between the two groups regarding the time (in hours) until reaching a target heart rate below 100 beats/min was observed. BB were found to decrease the heart rate after 5 hours (range 4-14) vs. 8 hours (range 4-18) for CCB (P = 0.009). Patients diagnosed with new-onset AF exhibited shorter duration of hospitalization after therapy with BB compared to CCB (median 72 vs. 96 hours, P = 0.012) in the subgroup of patients discharged with persistent AF. There was no significant difference between CCB and BB regarding the duration of hospitalization (P = 0.4) in the total patient population.

Conclusions: BB therapy is more potent for rapid reduction of the heart rate compared to CCB and demonstrated better efficiency in shortening the duration of hospitalization in a subgroup of patients. This finding should be reevaluated in subsequent research.

Disclaimer: Lupin makes no representation or warranty of any kind, expressed or implied, regarding the accuracy, adequacy, validity, reliability, availability, or completeness of any scientific information shared by the HCP on the STAR UPDATE podcast. You should not allow the contents of this to substitute for your own medical judgment, which you should exercise in evaluating the information on this website.

View Details

Abstract

The harm of heart failure mainly causes patients to develop dyspnea, fatigue, fluid retention, and other symptoms, which impair patients' activity tolerance and lead to a dramatic decrease in patients' quality of life. The purpose of this study was to verify whether metoprolol regulates AKAP5 expression and test the role of AKAP5 postinjury in mitigating cardiac infarction-associated tissue remodeling and fibrosis. Sprague-Dawley (SD) rats underwent coronary artery ligation (CAL), which was followed immediately with metoprolol daily. And western blot and coimmunoprecipitation experiments were performed to detect the expression of related proteins in the sham-operated group, model group, and drug-treated group. HW/BW ratio and cardiac expression of COL1 and COL3 were increased in rats following CAL compared with shams. Treatment with metoprolol postinjury was associated with a decrease in HW/BW ratio and COL1/COL3 expression compared to uncontrolled rats. CAL resulted in decreased cardiac AKAP5 expression compared to the control group, while metoprolol treatment restored levels compared to baseline shams. Cardiac expression levels of NFATc3/p-NFATc3 and GATA4 were modest at baseline and increased with injury, whereas metoprolol suppressed gene expression to below injury-associated changes. Immunoprecipitation indicated that AKAP5 could bind and regulate PP2B. In summary, we know that metoprolol alleviates ischemic cardiac remodeling and fibrosis, and the mechanism of alleviating remodeling may improve cardiac AKAP5 expression and AKAP5-PP2B interaction.

Disclaimer: Lupin makes no representation or warranty of any kind, expressed or implied, regarding the accuracy, adequacy, validity, reliability, availability, or completeness of any scientific information shared by the HCP on the STAR UPDATE podcast. You should not allow the contents of this to substitute for your own medical judgment, which you should exercise in evaluating the information on this website.

View Details

Abstract

Background: Ticagrelor is one of the most recent antiplatelet drugs to be approved to treat ischemic heart disease. Its efficacy may exceed aspirin in improving clinical outcomes in patients with acute ischemic stroke who are ineligible for rt-PA.

Objectives: We evaluated the safety regarding hemorrhagic complications (as a primary endpoint) and the efficacy (as a secondary endpoint) of a 180-mg loading dose of ticagrelor given within 9 h from the onset of the first-ever non-cardioembolic ischemic stroke.

Methods: We conducted our study on patients aged 18-75 years who presented with their first clinically manifested non-cardioembolic ischemic stroke and were recruited from the emergency department OF Kafr El-Sheik University Hospitals, Egypt. Eligible patients randomly received ticagrelor or aspirin loading and maintenance doses. Screening, randomization, and initiation of treatment all occurred within the first 9 h of stroke onset.

Results: Eighty-five patients received ticagrelor, and 84 received aspirin. Patients who received ticagrelor had a better clinical outcome in terms of NIHSS improvement at 2 days and 1 week of discharge and a favorable mRS score after 1 week of discharge and at 90-day follow-up. There was no significant difference between the two groups regarding hemorrhagic adverse effects.

Conclusion: This pilot study found that ticagrelor had a better clinical outcome than aspirin based on NIHSS and mRS in acute ischemic stroke patients who received it within 9 h from symptom onset and had a shorter hospital stay duration. Ticagrelor was non-inferior to aspirin regarding haemorrhagic complications.

Disclaimer: Lupin makes no representation or warranty of any kind, expressed or implied, regarding the accuracy, adequacy, validity, reliability, availability, or completeness of any scientific information shared by the HCP on the STAR UPDATE podcast. You should not allow the contents of this to substitute for your own medical judgment, which you should exercise in evaluating the information on this website.

View Details

Efficacy and Safety of Sustained-Release Metoprolol with Dronedarone After Radiofrequency Ablation of Paroxysmal Atrial Fibrillation: A Propensity Matched Analysis

Am J Cardiol. 2022 Oct 15;S0002-9149(22)00898-0

Abstract

The high early recurrence (ER) rate after radiofrequency catheter ablation (RFCA) seriously affects the prognosis of patients with atrial fibrillation (AF), and there are still controversies regarding the best preventive drugs for postoperative recurrence. A single-center retrospective study was conducted on patients with paroxysmal atrial fibrillation (PAF) who received metoprolol sustained-release tablets combined with dronedarone (observation group) and dronedarone alone (control group) after the first RFCA. A matching cohort was established using a 1:1 propensity score matching method to compare the incidence of ER, cardiac function, inflammation level, quality of life (QoL), and antiarrhythmic drugs (AADs)-related adverse reactions between groups. A total of 56 pairs of patients were successfully matched. The incidence of ER in the observation group was significantly lower than that in the control group (32% vs 14%, p = 0.033); the left atrial diameter in the observation group was significantly lower than that in the control group on Day 90 after RFCA (38 ±4 vs 40 ± 5, p = 0.021), and the QoL of the observation group was significantly improved on the thirtieth and ninetieth days after RFCA compared with the control group (72 ± 5 vs 69 ± 9, p = 0.031; 73 ± 4 vs 70 ± 9, p = 0.025). Multifactorial Cox analysis showed that diabetes mellitus, left atrial diameter >45 mm, ventricular rate >110 beats/min, and postoperative AADs were independent risk factors for ER in patients with PAF. The incidence of sinus bradycardia in the observation group was significantly higher than that in the control group (18% vs 3.6%, p = 0.029), but there was no statistical difference in the overall incidence of AADs-related adverse reactions between groups. Compared with dronedarone alone, dronedarone combined with metoprolol sustained-release tablets can significantly reduce ER after RFCA in patients with PAF and improve cardiac function and QoL, without increasing the AADs-related adverse reactions.

Disclaimer: Lupin makes no representation or warranty of any kind, expressed or implied, regarding the accuracy, adequacy, validity, reliability, availability, or completeness of any scientific information shared by the HCP on the STAR UPDATE podcast. You should not allow the contents of this to substitute for your own medical judgment, which you should exercise in evaluating the information on this website.

View Details

Incidence and predictors of heart failure after acute coronary Syndrome: The CORALYS registry

Int J Cardiol. 2022 Oct 25;S0167-5273(22)01658-8

Abstract

Background: Previous studies investigating predictors of Heart Failure (HF) after acute coronary syndrome (ACS) were mostly conducted during fibrinolytic era or restricted to baseline characteristics and diagnoses prior to admission. We assessed the incidence and predictors of HF hospitalizations among patients treated with percutaneous coronary intervention (PCI) for ACS.

Methods and results: CORALYS is a multicenter, retrospective, observational registry including consecutive patients treated with PCI for ACS. Patients with known history of HF or reduced left ventricular ejection fraction (LVEF) were excluded. Incidence of HF hospitalizations was the primary endpoint. The composite of HF hospitalization or cardiovascular death, and cardiovascular and all-cause death were the secondary endpoints. Predictors of HF hospitalizations and the impact of HF hospitalization on cardiovascular and all-cause death were assessed by means of multivariable Cox proportional hazards model.14699 patients were included. After 2.9 ± 1.8 years, the incidence of HF hospitalizations was 12.7%. Multivariable analysis identified age, diabetes, chronic kidney disease, previous myocardial infarction, atrial fibrillation, pulmonary disease, GRACE risk-score ≥ 141, peripheral artery disease, cardiogenic shock at admission and LVEF ≤40% as independently associated with HF hospitalizations. Complete revascularization was associated with a lower risk of HF (HR 0.46,95%CI 0.39-0.55). HF hospitalization was associated with higher risk of CV and all-cause death (HR 1.89,95%CI 1.5-2.39 and HR 1.85,95%CI 1.6-2.14, respectively).

Conclusions: Incidence of HF hospitalizations among patients treated with PCI for ACS is not negligible and is associated with detrimental impact on patients' prognosis. Several variables may help to assess the risk of HF after ACS.

Disclaimer: Lupin makes no representation or warranty of any kind, expressed or implied, regarding the accuracy, adequacy, validity, reliability, availability, or completeness of any scientific information shared by the HCP on the STAR UPDATE podcast. You should not allow the contents of this to substitute for your own medical judgment, which you should exercise in evaluating the information on this website.

View Details

Effect of β-Blocker Therapy on the Level of Soluble ST2 Protein in Pediatric Dilated Cardiomyopathy

Medicina (Kaunas). 2022 Sep 23;58(10):1339

Abstract

Background and Objectives: A prognosis for kids with pediatric dilated cardiomyopathy (PDCM) is urgently needed to identify high-risk patients. This study aimed to determine the association of levels and soluble suppression of tumorigenicity 2 (sST2) and medical therapy of β-blocker inhibitors with the risk of adverse events in PDCM. Materials and Methods: A total of 124 patients with PDCM were enrolled after admission from 2 centers in China and followed up for adverse events (death, cardiac transplantation, and heart-failure-related rehospitalization). Based on a median sST2 level and the usage of β-blocker inhibitors, patients were divided into four groups. The Cox proportional hazard model was used to assess the risk of incident adverse events. Results: The median level of sST2 was 23.77 ng/mL, and 53 (42.7%) patients received β-blocker treatment. Over a median follow-up of 678 days, 37 (29.8%) adverse events occurred. Compared with patients with sST2 < median and without β-blocker, patients with sST2 ≥ median and without β-blocker (HR: 7.01; 95% CI: 1.21-40.45), followed by those with sST2 ≥ median and use of β-blocker had the highest risk of adverse events (hazard ratio (HR): 5.51; 95% confidence interval (CI): 1.17-25.84). However, a significant association was not observed in patients with sST2 < median and use of β-blocker. These associations were consistent across different subgroups. Conclusions: A higher level of sST2 was associated with a higher risk of adverse events in patients with PDCM, and β-blocker treatment for children with high levels of sST2 can effectively avoid adverse events.

Disclaimer: Lupin makes no representation or warranty of any kind, expressed or implied, regarding the accuracy, adequacy, validity, reliability, availability, or completeness of any scientific information shared by the HCP on the STAR UPDATE podcast. You should not allow the contents of this to substitute for your own medical judgment, which you should exercise in evaluating the information on this website.

View Details

Clopidogrel resistance and ticagrelor replacement in dual antiplatelet therapy for carotid artery stenting

Ann Vasc Surg. 2022 Oct 18;S0890-5096(22)00640-9

Abstract

Objective: Resistance to the pharmacological effect of clopidogrel in patients undergoing dual antiplatelet therapy for carotid stenting may increase the risk of periprocedural neurological events. The purpose of the study was to describe the phenomenon of clopidogrel resistance in a series of patients undergoing carotid stenting.

Methods: Data of patients who consecutively underwent carotid stenting from 11/2016 to 12/2020 for a significant stenosis and who underwent a dual antiplatelet therapy using acetyl-salicylic acid and clopidogrel were prospectively collected. Patients who were already taking a different thienopyridine were excluded. The effectiveness of antiplatelet drugs was assessed by the impedance aggregometry test. Primary endpoint was to evaluate the incidence of clopidogrel resistance and the effectiveness of ticagrelor as alternative therapy. P values <0.05 were considered statistically significant.

Results: Two-hundred patients (80 females, 40%;) underwent stenting for carotid stenosis (94% asymptomatic). The phenomenon of clopidogrel resistance was observed in 38 patients (19%), in whom clopidogrel was replaced by ticagrelor (90 mg/bis in die) with 100% effectiveness at aggregometry test. Platelet counts was associated to clopidogrel resistance (P=0.001). There was no stent thrombosis at 30 days, neither major hemorrhagic events; a total of 12/200 major adverse cardiovascular events occurred (6%), including 1 in the group of patients who took ticagrelor and 11 in group of patients under clopidogrel (2.6% vs 6.7%, P = 0.55).

Conclusions: Clopidogrel was ineffective in 19% of patients undergoing carotid stenting. Platelet count seemed to affect this phenomenon. In these patients, clopidogrel was effectively replaced by ticagrelor

Disclaimer: Lupin makes no representation or warranty of any kind, expressed or implied, regarding the accuracy, adequacy, validity, reliability, availability, or completeness of any scientific information shared by the HCP on the STAR UPDATE podcast. You should not allow the contents of this to substitute for your own medical judgment, which you should exercise in evaluating the information on this website.

View Details

Abstract

Results: Following a literature search, 340 publications were found. Finally, 18 studies were included for the systematic review, and 8 clinical trials were included in the meta-analysis after the full-text screening. At 6 months, the pooled effect revealed a statistically significant association between Metoprolol and increased left ventricular ejection fraction (LVEF) (%) compared to controls (mean difference [MD] = 3.57, [95% confidence interval [CI] = 2.22-4.92], p < .00001), as well as decreased infarcted myocardium(g) compared to controls (MD = -3.84, [95% [CI] = -5.75 to -1.93], p < .0001). At 1 week, the pooled effect revealed a statistically significant association between Metoprolol and increased LVEF (%) compared to controls (MD = 2.98, [95% CI = 1.26-4.69], p = .0007), as well as decreased infarcted myocardium (%) compared to controls (MD = -3.21, [95% CI = -5.24 to -1.18], p = .002).

Conclusion: A significant decrease in myocardial infarction and increase in LVEF (%) was linked to receiving Metoprolol at 1 week and 6-month follow-up.

Disclaimer: Lupin makes no representation or warranty of any kind, expressed or implied, regarding the accuracy, adequacy, validity, reliability, availability, or completeness of any scientific information shared by the HCP on the STAR UPDATE podcast. You should not allow the contents of this to substitute for your own medical judgment, which you should exercise in evaluating the information on this website.

View Details

Abstract

Background: Thromboembolic complications are one of the major periprocedural complications following neuroendovascular procedures. Dual antiplatelet therapy (DAPT) with aspirin and clopidogrel remain the principal agents for prevention of thromboembolic complications. However, clopidogrel resistance is associated with higher risk of thromboembolic complications. This study investigated the safety and efficacy of DAPT with ticagrelor and aspirin in patients undergoing intracranial stenting procedures.

Methods: This retrospective study was based on patients with intracranial aneurysms who undergoing intracranial stenting procedures at our institution between August 2017 and July 2020. These patients received DAPT with ticagrelor and aspirin were included. DAPT with 90 mg ticagrelor twice-daily and aspirin 100 mg daily was continued for 3 months after the intracranial stenting procedure and aspirin continued for 1 year.

Results: In this study, 151 patients were identified. The most common aneurysm location was the internal carotid artery with 127 (71.8%) patients. Of the 151 cases with 160 treated aneurysms, 30 (18.8%) patients were treated by flow diverters (FDs), and 130 (81.2%) by stent-assisted coiling. Five (3.3%) patients had thromboembolic complications. Intraprocedural aneurysmal rupture was observed in one patient as a result of coil extrusion during coil insertion. None of the patients showed a newly DAPT-related intracerebral hemorrhage. Two patients developed dyspnea, and the symptom resolved without intervention. Furthermore, ecchymoma and gastrointestinal bleeding occurred in one patient respectively. DAPT-related thromboembolic and hemorrhagic complications were not significantly different between the FD group and stent-assisted coiling group.

Conclusions: In our study, DAPT combining ticagrelor and aspirin seems to bea safe and efficient treatment for preventing thromboembolic complications in patients with intracranial aneurysms, without any increase in hemorrhagic complications. Ticagrelor may be an effective alternative for patients undergoing neurointervention.

Disclaimer: Lupin makes no representation or warranty of any kind, expressed or implied, regarding the accuracy, adequacy, validity, reliability, availability, or completeness of any scientific information shared by the HCP on the STAR UPDATE podcast. You should not allow the contents of this to substitute for your own medical judgment, which you should exercise in evaluating the information on this website.

View Details

The study is a double-blind, placebo-controlled, randomized TWILIGHT trial (Ticagrelor with Aspirin or Alone in High-Risk Patients After Coronary Intervention) that compared the use of ticagrelor with or without aspirin in the patients undergoing PCI. The study enrolled patients undergoing high-risk percutaneous coronary intervention. After 3 months of treatment with ticagrelor plus aspirin, event-free and adherent patients remained on ticagrelor and were randomly assigned to receive aspirin or placebo for 1 year. Out of 9006 enrolled and 7119 randomized patients in TWILIGHT, 1169 patients were enrolled at 27 Chinese sites in this prespecified sub study, of whom 1028 patients were randomized after 3 months. The incidence of the primary end point was 6.2% in the ticagrelor+aspirin group versus 3.5% in the ticagrelor + placebo group between randomization and 1 year. The key secondary end point occurred in 3.4% of patients in the ticagrelor+aspirin group versus 2.4% in the ticagrelor+placebo group. There was no interaction between the region of randomization (China versus the rest of the world) and randomized treatment assignment in terms of the primary or key secondary end points. The study concluded thatTicagrelor monotherapy significantly reduced clinically relevant bleeding without increasing ischemic events as compared with ticagrelor plus aspirin in Chinese patients undergoing high-risk percutaneous coronary intervention.

Disclaimer: Lupin makes no representation or warranty of any kind, expressed or implied, regarding the accuracy, adequacy, validity, reliability, availability, or completeness of any scientific information shared by the HCP on the STAR UPDATE podcast. You should not allow the contents of this to substitute for your own medical judgment, which you should exercise in evaluating the information on this website.

View Details

Ticagrelor provides more rapid, potent, and consistent anti-platelet efficacy than clopidogrel. This study is a randomized trial that aimed to evaluate the anti-inflammatory effects of ticagrelor on thrombus aspirated from the ST-elevation myocardial infarction (STEMI) patients. The results were compared against clopidogrel.

The study was conducted among 98 patients with STEMI and intended percutaneous coronary intervention (PCI). The patients were divided into two groups to receive clopidogrel (600-mg loading dose) or ticagrelor (180-mg loading dose).

As compared with the clopidogrel group, the number of total inflammatory cells per mm2 thrombus area in the ticagrelor group was decreased by 28%. The numbers of neutrophils and myeloperoxidase-positive cells per mm2 thrombus area in the ticagrelor group were decreased by 35% and 28% respectively, as compared with those in the clopidogrel group. Moreover, ticagrelor treatment reduced the ratio of monocytes number higher than 250 per mm2 thrombus area compared with clopidogrel treatment (4% versus 29%, P = 0.048).

The study concluded thatin patients with undergoing PCI for STEMI, the loading dose ticagrelor regimen was associated with a reduction in inflammatory cell infiltration within thrombus compared with the loading dose clopidogrel regimen.

Disclaimer: Lupin makes no representation or warranty of any kind, expressed or implied, regarding the accuracy, adequacy, validity, reliability, availability, or completeness of any scientific information shared by the HCP on the STAR UPDATE podcast. You should not allow the contents of this to substitute for your own medical judgment, which you should exercise in evaluating the information on this website.

View Details

Beta-blockers in acute coronary syndrome: does rhythm matter?

The study aimed to assess and compare the in-hospital and 1-year prognostic impact of BB prescription after acute coronary syndrome (ACS), in patients with previous or de novo AF, and in patients with sinus rhythm (SR). It has been already known that beta-blockers (BB) are recommended in patients with previous acute myocardial infarction (AMI), aiming to reduce morbidity and mortality. Their benefit is greater in patients with associated left ventricular dysfunction. However, in patients with atrial fibrillation (AF), its prognostic benefit is controversial.

The study was conducted as a multicentre retrospective trial conducted among 35279 patients hospitalized for ACS. The patients were divided into two groups according to the prescription or not of beta-blocker (BB). The impact of BB prescription on in-hospital and 1-year mortality rates, in patients with AF versus SR, was compared.

Out of 35279 patients, 14906 patients were selected. Around 82.5% of patients had a BB prescription and 17.5% were without a BB prescription. Patients without BB prescription were older and had more comorbidities, namely valvular disease and chronic pulmonary obstructive disease The mean left ventricular ejection fraction was 53±13% in patients without BB prescription and 52±11 in the group with BB prescription. In-hospital and after discharge BB prescription was less frequent in AF patients. BB prescription was associated with a lower in-hospital mortality rate regardless of the rhythm, with an 81% risk reduction in SR and 79% in AF patients.

To conclude,BB prescription was associated with reduced in-hospital and 1-year mortality rates. The prognostic benefit of BB therapy was equivalent in ACS patients in sinus rhythm and with previous or new-onset AF.

Disclaimer: Lupin makes no representation or warranty of any kind, expressed or implied, regarding the accuracy, adequacy, validity, reliability, availability, or completeness of any scientific information shared by the HCP on the STAR UPDATE podcast. You should not allow the contents of this to substitute for your own medical judgment, which you should exercise in evaluating the information on this website.

View Details

Metoprolol improves left ventricular longitudinal function at rest and during exercise in obstructive hypertrophic cardiomyopathy

The following study aimed to characterize left ventricular (LV) systolic function by segmental and global longitudinal strain echocardiography and to investigate changes in relation to exercise, and the effect of standard treatment with beta-blockers. What we already know is that hypertrophic cardiomyopathy (HCM) patients with outflow obstruction often experience symptoms of heart failure upon exertion.

A total of 29 with obstructive HCM and New York Heart Association (NYHA) class ≥ II symptoms were enrolled in a double-blind, placebo-controlled, randomized crossover trial. These patients received metoprolol 150 mg or placebo for two consecutive two-week periods in random order. Echocardiographic assessment with speckle-tracking derived longitudinal strain (LS) was performed at rest and during peak exercise at the end of each treatment period. Segmental LS was calculated as the mean of the six apical, mid, and basal segments.

Coming to the results,treatment with metoprolol improves the LS of the apical segment and mid-segment. The segmental improvement with metoprolol treatment was reflected in an increase in global longitudinal strain for LV function (LV GLS).Peak exercise was associated with a reduction in LV GLS, yet the improvement in LV GLS with metoprolol treatment was consistent upon exercise.

To conclude,systolic performance assessed by LV GLS showed impaired values at rest and during exercise, with severely depressed values of the mid and basal segments. Treatment with metoprolol improved segmental strain and LV GLS upon exercise, indicating a beneficial effect of beta-blocker therapy on LV systolic function.

Disclaimer: Lupin makes no representation or warranty of any kind, expressed or implied, regarding the accuracy, adequacy, validity, reliability, availability, or completeness of any scientific information shared by the HCP on the STAR UPDATE podcast. You should not allow the contents of this to substitute for your own medical judgment, which you should exercise in evaluating the information on this website.

View Details

Bleeding outcomes with ticagrelor versus clopidogrel in patients with the acute coronary syndrome; a focused analysis from the multicenter CREA ARIAM Andalucia registry

The question that usually arises is that, “What is the incidence, types, timing, and prognostic relevance of major bleeding events in ACS patients treated with ticagrelor or clopidogrel in contemporary practice”? What we already know is that with the use of various antithrombotic agents in acute coronary syndrome (ACS), bleeding has emerged as an important safety concern. Moreover, haemorrhagic complications have been strongly linked with subsequently mortality in this clinical scenario.

A total of 2070 patients with ACS were enrolled in the prospective, observational, multicentre trial. The participants received a 12-month DAPT course with clopidogrel or ticagrelor. Major bleeding was assessed using the Bleeding Academic Research Consortium (BARC). All bleeding episodes were analysed accounting for death. Among 2070 patients surviving hospital discharge, 5.3% (106) of them experienced a major bleeding event at the median time of 92 days and most events were classified as BARC type 3a with 2 fatal bleeds.

In 53% of the cases, the site was gastrointestinal bleeding followed by 12% cases of intracranial bleeding. Ticagrelor was associated with an increased but not statistically significant risk of major bleeding compared with clopidogrel. To conclude,the most common bleeding site was gastrointestinal site followed by intracranial haemorrhage and the ticagrelor use was not associated with a significantly increased risk of major bleeding.

Disclaimer: Lupin makes no representation or warranty of any kind, expressed or implied, regarding the accuracy, adequacy, validity, reliability, availability, or completeness of any scientific information shared by the HCP on the STAR UPDATE podcast. You should not allow the contents of this to substitute for your own medical judgment, which you should exercise in evaluating the information on this website.

View Details

Conservative management in a contemporary cohort of patients with acute coronary syndrome: Results from the FORCE-ACS registry

The study aimed to evaluate conservative management compared with revascularization therapy in ACS patients, focused on ischemic and bleeding outcomes and to provide insights into the physician’s rationale of choice for conservative management. Currently, the evidence for conservatively managed patients with the acute coronary syndrome (ACS) is scarce.

A total of5379 ACS patients were enrolled in the FORCE-ACS registry. Patients without coronary revascularization were identified and classified into three groups: patients where no coronary angiography (CAG) was performed, patients with documented obstructive coronary artery disease (CAD) on CAG, and patients with no documented obstructive CAD on CAG. The first two groups were established as conservatively managed ACS patients and were compared with those who received coronary revascularization.

Talking about the results,a total of 5379 patients were admitted with ACS, 93.8% of them underwent CAG and 19.9% of the patients did not receive coronary revascularization. The most frequent reasons for choosing conservative management in ACS patients included multi-comorbidity, complex coronary anatomy, or a "watchful waiting" strategy. 84.5% conservatively treated patients received dual or triple antithrombotic therapy less often than the revascularized group, i.e 94.6% patients

To conclude, conservatively managed patients are at higher mortality risk than revascularized patients. This heterogeneous group of conservatively managed patients less often received guideline-recommended therapy.

Disclaimer: Lupin makes no representation or warranty of any kind, expressed or implied, regarding the accuracy, adequacy, validity, reliability, availability, or completeness of any scientific information shared by the HCP on the STAR UPDATE podcast. You should not allow the contents of this to substitute for your own medical judgment, which you should exercise in evaluating the information on this website.

View Details

Abstract

The occurrence of coronary artery embolism (CE) has been associated with various clinical conditions, including aortic and mitral prosthetic heart valve implantation, atrial fibrillation (AF), dilated cardiomyopathy, neoplasia, infective endocarditis, atrial septal defect, cardiac tumors, and hypercoagulable states. CE is also a rare cause of myocardial infarction (MI), with a prevalence of about 5%, a figure probably underestimated. The purpose of this article was to determine the current state of knowledge on acute coronary syndrome (ACS) related to CE. We thus performed a comprehensive structured literature search of the MEDLINE database for articles published between 1 January 1990 and 31 December 2021. The diagnosis of CE remains difficult despite the currently used Shibata classification, which is based on major criteria, including angiographic characteristics: globular filling defects, saddle thrombi or multiple filling defects and absence of atherosclerosis in the coronary arteries. Suspected or confirmed CE requires the identification of an etiology. There are only two published series on CE, including about 50 cases each. The three main causes in these series were: 1) atrial fibrillation (73% vs 28.3%), 2) cardiomyopathy (9.4% vs 25%) and 3) malignancy (9.6% vs 15.1%). Finally, 26.3% of the MI patients with CE had no identifiable cause of CE. When anatomically possible, analyzing the thrombus after thrombectomy may help. MI due to CE requires systematic assessment of other locations, i.e., multiple coronaries and extracardiac locations. Simultaneous systemic embolization to the brain (67%), limbs (25%), kidneys (25%) or spleen (4%) is frequent, occurring in approximately 25% of CE-related MI. In the setting of acute MI, CE is associated with significant morbidity and mortality. Coronary artery thromboembolism is a rare, non-atherosclerotic, cause of ACS, and prospective studies are needed to evaluate a systematic diagnostic approach and personalized therapeutic strategies.

Cardiovasc Med. 2022 Jul 19;S1050-1738(22)00107-4.

Disclaimer: Lupin makes no representation or warranty of any kind, expressed or implied, regarding the accuracy, adequacy, validity, reliability, availability, or completeness of any scientific information shared by the HCP on the STAR UPDATE podcast. You should not allow the contents of this to substitute for your own medical judgment, which you should exercise in evaluating the information on this website.

View Details

Abstract

Introduction: Patients undergoing acute percutaneous coronary intervention receive dual antiplatelet therapy for secondary prevention. Recurrent myocardial infarction or bleedings are possibly due to under- or overdosing of antiplatelet therapy in relation to body size.

Methods: We correlated residual platelet aggregation with body mass index, body surface area, lean body mass and blood volume in 220 patients on prasugrel (n = 121) or ticagrelor (n = 99).

Results: Platelet aggregation outside the recommended window was recorded in 85 patients, but not correlated with any of the body indices.

Conclusion: Body size does not affect platelet response to prasugrel or ticagrelor at the guideline-recommended fixed dosages.

Vascul Pharmacol. 2022 Jul 20;107089.

Disclaimer: Lupin makes no representation or warranty of any kind, expressed or implied, regarding the accuracy, adequacy, validity, reliability, availability, or completeness of any scientific information shared by the HCP on the STAR UPDATE podcast. You should not allow the contents of this to substitute for your own medical judgment, which you should exercise in evaluating the information on this website.

View Details

Abstract

Objective: Beta-blockers are first-line anti-impulse therapy in patients presenting with acute type B aortic dissection (TBAD). However, little is understood about their impact after aortic repair. The aim of this study was to evaluate the role of postoperative beta-blocker use on outcomes of thoracic endovascular aortic repair (TEVAR) in TBAD.

Methods: The Vascular Quality Initiative database was queried for all patients undergoing TEVAR for TBAD from 2012 to 2020. Aortic-related reintervention, all-cause mortality and effect of TEVAR on false lumen thrombosis of the treated aortic segment were assessed and compared between patients treated with and without beta-blocker postoperatively. Cox proportional hazards models were used to estimate the effect of beta-blocker therapies on outcomes.

Results:1,114 patients undergoing TEVAR for TBAD were identified with a mean follow-up of 18±12 months. The mean age was 61.1±11.9 years, and 791 (71%) were male. 935 (84%) patients were maintained on beta-blocker at discharge and follow-up. Patients on beta-blocker were more likely to have an entry tear originating in zones 1-2 (22% vs 13%; P=.022). The prevalence of acute, elective and symptomatic AD, concurrent aneurysm, number of endografts used, distribution of the proximal and distal zones of dissection and operative time were comparable between the two cohorts. At 18-months, significantly more complete false lumen thrombosis (58 vs 47%; log-rank P=.018) was observed in patients on beta-blocker while the rates of aortic-related reinterventions (13% vs 9%; log-rank P=.396) and mortality (0.2% vs 0.7%; log-rank P=.401) were similar in patients with and without beta-blocker, respectively. Even after adjusting for clinical and anatomic factors, postoperative beta-blocker use was associated with increased complete false lumen thrombosis (HR 1.56; 95% CI: 1.10-2.21; P=.012) but did not affect mortality or aortic-related reintervention. A secondary analysis of beta-blocker use in acute versus chronic TBAD showed a higher rate of complete false lumen thrombosis in patients on beta-blocker in chronic TBAD (59% vs 38%; log-rank P=.038). In contrast, there was no difference in the rate of complete false lumen thrombosis in acute TBAD between the two cohorts (58% vs 51%; log-rank P=.158). When analyzed separately, postoperative ACE inhibitor use did not affect the rates of complete false lumen thrombosis, mortality and aortic-related reintervention.

Conclusions: Beta-blocker use was associated with promotion of complete false lumen in patients undergoing TEVAR for TBAD. In addition to its role in acute setting, anti-impulse control with beta-blocker appears to confer favorable aortic remodeling.

and may improve outcomes after TEVAR, particularly for chronic TBAD.

J Vasc Surg. 2022 Jul 19;S0741-5214(22)01936-X.

Disclaimer: Lupin makes no representation or warranty of any kind, expressed or implied, regarding the accuracy, adequacy, validity, reliability, availability, or completeness of any scientific information shared by the HCP on the STAR UPDATE podcast. You should not allow the contents of this to substitute for your own medical judgment, which you should exercise in evaluating the information on this website.

View Details

Abstract

Background: This meta-analysis mainly aimed to compare the impact of prasugrel and ticagrelor on platelet reactivity (PR) in patients with acute coronary syndrome (ACS).

Methods: We searched four electronic databases to identify randomized controlled trials and cohort studies comparing the impact of prasugrel and ticagrelor on PR in patients with ACS. We performed group analyses according to three detection methods, drug dose [loading dose (LD) and maintenance dose (MTD)] and LD effect time, and assessed the robustness of the results through sensitivity analysis.

Results: Twenty-five studies with 5,098 patients were eligible. After LD, the incidence of high on-treatment platelet reactivity (HTPR) of ticagrelor was significantly lower than that of prasugrel within 6-18 h based on vasodilator-stimulated phosphoprotein (VASP) test [RR = 0.25 (0.07, 0.85), P = 0.03], there was no significant difference between ticagrelor and prasugrel in the following results: platelets inhibitory effect within 24-48 h based on VerifyNow P2Y12 (VN) assay (P = 0.11) and VASP test (P = 0.20), and the incidence of HTPR within 2-6 h based on VN assay (P = 0.57) and within 24-48 h based on VN assay (P = 0.46) and VASP test (P = 0.72), the incidence of low on-treatment platelet reactivity (LTPR) within 6-18 h based on VASP test (P = 0.46) and 48 h based on VN assay (P = 0.97) and VASP test (P = 0.73). After MTD, the platelet inhibitory effect of ticagrelor was stronger than that of prasugrel based on VN assay [WMD = -41.64 (-47.16, -36.11), P < 0.00001]and VASP test [WMD = -9.10 (-13.88, -4.32), P = 0.0002], the incidence of HTPR of ticagrelor was significantly lower than that of prasugrel based on VN assay [RR = 0.05 (0.02, 0.16), P < 0.00001], the incidence of LTPR of ticagrelor was significantly higher than prasugrel based on VN assay [RR = 6.54 (4.21, 10.14), P < 0.00001] and VASP test [RR = 2.65 (1.78, 3.96), P < 0.00001], the results of Multiple Electrode Aggregometry (MEA) test was inconsistent with the other two detection methods in platelet inhibitory effect and the incidence of HTPR and LTPR. There was no significant difference between ticagrelor and prasugrel in the following clinical outcomes: all-cause death (P = 0.86), cardiovascular death (P = 0.49), myocardial infarction (P = 0.67), stroke (P = 0.51), target vessel revascularization (P = 0.51), stent thrombosis (P = 0.90), TIMI major bleeding (P = 0.86) and bleeding BARC type ≥ 2 (P = 0.77). The risk of bleeding BARC type 1 of ticagrelor was significantly higher than prasugrel [RR = 1.44 (1.03, 2.02), P = 0.03].

Conclusions: Compared with prasugrel, ticagrelor might have a stronger platelet inhibition effect, with a lower incidence of HTPR and a higher incidence of LTPR and bleeding BARC type 1, while there might be no significant difference in the risk of thrombosis/ischemic, bleeding BARC Type ≥ 2 and TIMI major bleeding. A higher incidence of LTPR might indicate a higher risk of bleeding BARC type 1. The results of VN assay were consistent with that of VASP test, and not with the MEA test.

Front Cardiovasc Med. 2022 Jun 9; 9:905607

Disclaimer: Lupin makes no representation or warranty of any kind, expressed or implied, regarding the accuracy, adequacy, validity, reliability, availability, or completeness of any scientific information shared by the HCP on the STAR UPDATE podcast. You should not allow the contents of this to substitute for your own medical judgment, which you should exercise in evaluating the information on this website.

View Details

· ST-segment elevation myocardial infarction (STEMI) and non-ST-segment elevation acute (NSTE-ACS) coronary syndrome are referred to collectively as acute coronary syndrome (ACS)

· The latter includes non-ST-segment elevation myocardial infarction and unstable angina pectoris (NSTEMI). Cardiovascular catheterization must be immediately recommended in cases of STEMI.

· The management and diagnosis of NSTE-ACS are more difficult. The most recent ESC treatment guidelines for NSTE-ACS were released in 2020 which cover the areas of diagnosis, risk assessment, antithrombotic therapy, invasive or non-invasive coronary diagnostics, and long-term management.

· In order to enable a quick triage decision (rule-in as possible NSTEMI or rule-out as NSTEMI excluded) in the emergency room or the chest pain unit, the guidelines put a focus on the deployment of high-sensitivity cardiac troponin assays combined with established diagnostic algorithms.

Disclaimer: Lupin makes no representation or warranty of any kind, expressed or implied, regarding the accuracy, adequacy, validity, reliability, availability, or completeness of any scientific information shared by the HCP on the STAR UPDATE podcast. You should not allow the contents of this to substitute for your own medical judgment, which you should exercise in evaluating the information on this website.

View Details

The authors aimed to determine the efficacy of comprehensive pharmaceutical care intervention that included face-to-face education about the disease, healthy lifestyle, medication adherence, drug related problems management and goal setting which was added to cardiac rehabilitation program in improving echocardiographic parameters, nutritional status and High sensitivity C-Reactive Protein in patients with acute coronary syndrome. In this study, out of a total of 40 patients, 20 patients were randomized to the control group and 20 patients were randomized to the intervention group.

The following are key points to remember from this prospective study on the management of post ACS patients randomized to receive pharmaceutical care intervention:

· In comparison to the control group, the intervention group demonstrated significant decrease in left ventricular end systolic volume and left ventricular end diastolic volume

· Additionally, intervention group showed significant increase in nutritional status and also increased the patients’ knowledge about the disease and drugs

· However, no significant changes were observed in HS-CRP levels between intervention and the control group

· According to this study, CR regimens that integrated comprehensive pharmacological treatment dramatically improved cardiac metrics and nutritional health. The simplest way to explain this is through improving adherence to cardiovascular drugs and improving dosage and awareness of medications.

· Implementing Comprehensive pharmaceutical care intervention added to CR programs could improve the cardiac function and nutritional status of post-acute coronary syndrome patients.

Disclaimer: Lupin makes no representation or warranty of any kind, expressed or implied, regarding the accuracy, adequacy, validity, reliability, availability, or completeness of any scientific information shared by the HCP on the STAR UPDATE podcast. You should not allow the contents of this to substitute for your own medical judgment, which you should exercise in evaluating the information on this website.

View Details

The authors aimed to evaluate the effects of metoprolol succinate in combination with Entresto (Sacubitril Valsartan Sodium Tablets) on cardiac function and coagulation function in patients with congestive heart failure (CHF). A total of 120 patients were included in this study and patients were randomly assigned to control group and study group. In the control group, patients were prescribed with metoprolol succinate sustained-release tablets and the patients in the study group were prescribed with metoprolol succinate sustained-release tablets combined with Entresto.

The following are key points to remember from this study on the management of patients with CHF treated with metoprolol succinate sustained-release tablets combined with Entresto:

Take-Home Message No. 1

While comparing the clinical efficacy, the effective rates of study group and the control group were 98.33% and 90%, respectively.

Take-Home Message No. 2

Before the treatment, no significant differences in cardiac function indexes and vascular endothelial function were observed. After the treatment in the study group, LVESD and LVEDD decreased and LVEF increased.

Take-Home Message No. 3

In the study group, the levels of CGRP and ET increased but the levels of NO decreased after the treatment.

Take-Home Message No. 4

No significant difference was observed in oxidative stress indexes before the treatment. After the treatment, levels of GSH-Px and SOD increased and the levels of MDA decreased in the study group.

Take-Home Message No. 5

While comparing the indexes of blood coagulation function, no significant differences were observed before the treatment but after the treatment, levels of APTT, PT, and FIB in the study group decreased.

Take-Home Message No. 6

Clinical studies showed that in CHF patients receiving Entresto and metoprolol together, LVESD and LVEDD reduced and LVEF increased, effectively promoting heart function and vascular endothelial function and lowering oxidative stress, blood coagulation indices, indicating that Entresto in combination with Metoprolol has good safety when improving ventricular remodelling.

Disclaimer: Lupin makes no representation or warranty of any kind, expressed or implied, regarding the accuracy, adequacy, validity, reliability, availability, or completeness of any scientific information shared by the HCP on the STAR UPDATE podcast. You should not allow the contents of this to substitute for your own medical judgment, which you should exercise in evaluating the information on this website.

View Details

Observational studies that failed to take time-dependent confounders into account have lately called into doubt the net therapeutic advantage of ticagrelor over clopidogrel in acute coronary syndrome (ACS). The authors aimed to evaluate the comparative safety and efficacy of ticagrelor vs. clopidogrel in real-life setting by taking into account the non-adherence of the therapy.

The following are key points to remember from this prospective, multi-cohort study on the outcomes in ACS patients discharged on ticagrelor or clopidogrel:

Out of a total of 2070 patients, 1,035 patients were discharged on ticagrelor and clopidogrel, respectively.
When compared to clopidogrel users, patients on ticagrelor were younger and had fewer comorbidities, but had higher rates of drug non-compliance. In comparison to clopidogrel, ticagrelor did not increase the risk of severe bleeding after extensive multivariate adjustments.
In comparison to clopidogrel, Ticagrelor resulted in clinical net benefit by showing a superiority in reduction of MACE events, vascular death, and definite probable stent thrombosis.
The results of the sensitive analysis and primary analysis were consistent whereas results from the intention intention-to-treat (ITT) analysis were found in the opposite direction.
When compared to clopidogrel, ticagrelor produced a net therapeutic benefit among all-comers with ACS while not significantly raising the risk of severe haemorrhage.

Disclaimer: Lupin makes no representation or warranty of any kind, expressed or implied, regarding the accuracy, adequacy, validity, reliability, availability, or completeness of any scientific information shared by the HCP on the STAR UPDATE podcast. You should not allow the contents of this to substitute for your own medical judgment, which you should exercise in evaluating the information on this website.

View Details

Transcatheter aortic valve replacement (TAVR) has become a well-established therapy for patients with severe, symptomatic aortic stenosis who are at intermediate-to-high surgical risk over last decade. Aortic stenosis and coronary artery disease (CAD) have similar risk factors and pathogenic pathways, and 40% to 75% of TAVR patients had significant CAD.

In patients with severe CAD following aortic valve replacement, current recommendations advocate coronary revascularization (Class IIa, Level of Evidence: C). Patients who underwent TAVR at our facility on consecutive days between May 2007 and November 2017 were included. Patients were observed for one, six, and twelve months, and then once a year after that.

A total of 779 individuals were included in the study (, with 68% having a history of CAD. At the end of a median follow-up of 25 months, 78 patients (10%) had at least one episode of ACS, with half of the occurrences occurring within the first year after TAVR. Clinical presentation was type 2 non–ST-segment elevation myocardial infarction, unstable angina, type 1 non–ST-segment elevation myocardial infarction, and ST-segment elevation myocardial infarction. Male sex and nontransfemoral approach had an independent association with ACS. In-hospital death rate at the time of the ACS episode was 3.8%. At a median follow-up of 21 months post-ACS, all-cause and cardiovascular death rates were 37.3% and 25.3%, respectively.

After a median follow-up of 25 months, about one-tenth of patients who underwent TAVR were readmitted for an ACS. Male sex, prior CAD, and nontransfemoral method all predicted ACS independently. ACS was linked to a significant rate of midterm mortality.

Disclaimer: Lupin makes no representation or warranty of any kind, expressed or implied, regarding the accuracy, adequacy, validity, reliability, availability, or completeness of any scientific information shared by the HCP on the STAR UPDATE podcast. You should not allow the contents of this to substitute for your own medical judgment, which you should exercise in evaluating the information on this website.

View Details

Ticagrelor lowers ischemia risk in patients who have had a previous heart attack (MI). It's uncertain whether the risks of ischemic stroke and the advantages of long-term P2Y12 inhibition in this cohort are stable over time. The goal of the trial was to see how ischemia risk changed over time and if the efficacy and safety of ticagrelor were the same early and late after randomization.

The PEGASUS-TIMI (Prevention of Cardiovascular Events in Patients with Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin–Thrombolysis In Myocardial Infarction) 54 trial randomised patients with a prior MI (median 1.7 years prior) to ticagrelor 90 mg, ticagrelor 60 mg, or placebo on an aspirin background. At yearly checkpoints, the rates of CV death, MI, and stroke, as well as TIMI significant haemorrhage, were examined (years 1, 2, and 3).

A total of 21,162 individuals were randomised and observed for 33 months (median), with 28% of patients still suffering from MI five years after the trial ended. The risk of CV mortality, MI, or stroke in the placebo arm remained essentially stable at a 3% annualised rate throughout the trial. At each succeeding milestone, the benefit of ticagrelor 60 mg was consistent (year 1 hazard ratio [HR]: 0.82; 95 percent confidence interval [CI]: 0.67 to 0.99; year 2 HR: 0.90; 95 percent CI: 0.74 to 1.11; and year 3 HR: 0.79; 95 percent CI: 0.62 to 1.00). At each milestone, ticagrelor 60 mg increased TIMI major bleeding, with the greatest risk in the first year (year 1 HR: 3.22; year 2 HR: 2.07; year 3 HR: 1.65).

Even after more than 5 years, patients with past MI who are more than 1-year post-event are still at risk of repeat atherothrombotic events with no signs of declining risk. Ticagrelor reduced ischemia risk in patients who had previously had a MI, with consistent efficacy early and late and a trend toward less bleeding excess with time. These findings support the idea of continuing treatment in patients who tolerate the medicine well.

Disclaimer: Lupin makes no representation or warranty of any kind, expressed or implied, regarding the accuracy, adequacy, validity, reliability, availability, or completeness of any scientific information shared by the HCP on the STAR UPDATE podcast. You should not allow the contents of this to substitute for your own medical judgment, which you should exercise in evaluating the information on this website.

View Details

Patients at a high risk of bleeding (HBR) are a common subgroup of those receiving percutaneous coronary intervention (PCI). After a short period of dual antiplatelet treatment (DAPT), early aspirin discontinuation has emerged as a bleeding prevention technique. It has been demonstrated by TWILIGHT trial that ticagrelor monotherapy is an effective and safe bleeding prevention approach for high-risk PCI patients, following a short course of DAPT.

TWILIGHT-HBR was conducted with the pre-specified analysis of TWILIGHT trial to determine the treatment effects of ticagrelor monotherapy compared with ticagrelor plus aspirin in a contemporary high-bleeding risk group. In this trial, after 3 months of ticagrelor plus aspirin, event-free patients were randomized to 12 months of aspirin or placebo in addition to ticagrelor. The primary end point assessed was BARC type 2, 3, or 5 bleeding up to 1 year after randomization and the key secondary endpoint was the composite of all-cause death, MI, or stroke.

A total of 1064 (17.2%) patients were HBR. HBR patients were older, more frequently female and of non-white race compared with non-HBR patients. They had more cardiovascular risk factors such as hypertension, diabetes, and peripheral artery disease, and were less frequently active smokers. The results of the TWILIGHT-HBR group demonstrated that ticagrelor monotherapy reduced the incidence of the primary endpoint of BARC 2, 3 or 5 bleeding in comparison to ticagrelor plus aspirin in HBR. The results demonstrated that ticagrelor monotherapy did not increase ischaemic events, including death, MI or stroke, irrespective of HBR status.

In conclusion, aspirin discontinuation followed by aspirin monotherapy significantly reduced bleeding without increasing ischaemic events as compared to ticagrelor plus aspirin among HBR patients and absolute risk reduction in major bleeding was larger in HBR than non-HBR patients.

Disclaimer: Lupin makes no representation or warranty of any kind, expressed or implied, regarding the accuracy, adequacy, validity, reliability, availability, or completeness of any scientific information shared by the HCP on the STAR UPDATE podcast. You should not allow the contents of this to substitute for your own medical judgment, which you should exercise in evaluating the information on this website.

View Details

After a minimum term of dual antiplatelet medication, monotherapy with a P2Y12 inhibitor is an emerging strategy for reducing the risk of bleeding after percutaneous coronary intervention (PCI). This Ticagrelor with Aspirin or Alone in High-Risk Patients after Coronary Intervention (TWILIGHT) trial was designed to test the hypothesis that a 3-month course of dual antiplatelet therapy with ticagrelor plus aspirin followed by ticagrelor monotherapy is superior to ticagrelor plus aspirin in patients undergoing PCI who are at risk of ischemic or hemorrhagic complications.

In this double-blind trial, the effects of ticagrelor monotherapy vs. ticagrelor plus aspirin were examined with respect to clinically relevant bleeding among patients who were at high risk for bleeding or an ischemic event and had undergone PCI. A total of 7119 patients were randomized after 3 months.

Between the time span of randomization and 1 year, the primary endpoint incidence was found to 4% in patients who received ticagrelor plus placebo and 7.1% in patients who received ticagrelor plus aspirin with the hazard ratio of 0.56. Between the two groups, the difference in risk was found to be similar for BARC type 3 or 5 bleeding with 1% incidence in patients receiving ticagrelor plus placebo and 2% among patients receiving ticagrelor plus aspirin with the hazard ratio of 0.49.

The incidence of death from any cause nonfatal myocardial infarction, or nonfatal stroke was found to be 3.9% in both groups. In conclusion, this study demonstrates that ticagrelor monotherapy results in lower incidence of clinically relevant bleeding than ticagrelor plus aspirin with no evidence of death, myocardial infarction, or stroke among patients high-risk patients who underwent PCI and completed 3 months of dual antiplatelet therapy.

Disclaimer: Lupin makes no representation or warranty of any kind, expressed or implied, regarding the accuracy, adequacy, validity, reliability, availability, or completeness of any scientific information shared by the HCP on the STAR UPDATE podcast. You should not allow the contents of this to substitute for your own medical judgment, which you should exercise in evaluating the information on this website.

View Details

The optimal timing of oral P2Y12 inhibitors administration is not well-defined even though they remain the main-stay treatment in the management of patients with non–ST-segment elevation acute coronary syndrome. In the theoretical knowledge, administration of an oral P2Y12 inhibitor before defining coronary anatomy provides more ischemic protection while patients are waiting to undergo coronary angiography and reduces the risk of periprocedural thrombotic complications among those undergoing percutaneous coronary interventions.

A randomized, adaptive, open-label, multicentre clinical trial was conducted that included 1,449 patients. These patients were randomized to downstream or upstream oral P2Y12 inhibitor administration. The patients were randomly assigned to receive pre-treatment with ticagrelor before angiography (upstream group) or no pre-treatment (downstream group). In the downstream group, the patients were further randomized to receive ticagrelor or prasugrel. The authors of this study hypothesised that downstream strategy has an upper hand over upstream strategy on the combination of efficacy and safety events.

The results of this study demonstrates that there was no significant difference between downstream and upstream groups in terms of primary endpoint, a composite of death due to vascular causes; nonfatal myocardial infarction or nonfatal stroke. These results were confirmed w.r.t patients undergoing percutaneous coronary intervention and regardless of the timing of coronary angiography.

In conclusion, downstream and upstream oral P2Y12 inhibitor administration strategies were found to be associated with low incidence of ischemic and bleeding events and minimal difference in terms of numerical values were found between the groups.

Disclaimer: Lupin makes no representation or warranty of any kind, expressed or implied, regarding the accuracy, adequacy, validity, reliability, availability, or completeness of any scientific information shared by the HCP on the STAR UPDATE podcast. You should not allow the contents of this to substitute for your own medical judgment, which you should exercise in evaluating the information on this website.

View Details

In the TICO randomized clinical trial, stopping aspirin was tested as a bleeding reduction method after short-term dual anti-platelet treatment (DAPT). However, ticagrelor monotherapy has not been studied in patients with acute coronary syndromes solely (ACS). The objective of this study was to determine whether moving to ticagrelor monotherapy in patients with ACS treated with drug-eluting stents, after 3 months of DAPT lowers net adverse clinical events compared to ticagrelor-based 12-month DAPT.

This randomized controlled trial was conducted in 3056 patients with ACS treated with drug-eluting stents between August 2015 and October 2018 were included in this trial. The patients were randomized to receive ticagrelor monotherapy (90 mg twice daily) after 3-month DAPT (n = 1527) or ticagrelor-based 12-month DAPT (n = 1529). The primary outcomes assessed was a 1-year net adverse clinical event, defined as a composite of major bleeding and adverse cardiac and cerebrovascular events (death, myocardial infarction, stent thrombosis, stroke, or target-vessel revascularization).

Out of a total of 3056 patients who were randomized, only 2978 patients (97.4%) completed the trial. The occurrence of primary endpoint happened in 3.9% of patients receiving ticagrelor monotherapy after 3-month DAPT and in 5.9% of patients receiving ticagrelor-based 12-month DAPT with the and a hazard ratio of 0.66. After 3 months of DAPT therapy, major bleeding occurred in 1.7% of patients with ticagrelor monotherapy and in 3% of patients with ticagrelor-based 12-month DAPT with the hazard ration of 0.56. No major difference was observed between the incidence of major adverse cardiac and cerebrovascular events between the ticagrelor monotherapy after 3-month DAPT group and ticagrelor-based 12-month DAPT group.

The results of this study demonstrates that among patients with acute coronary syndrome treated with drug-eluting stents, in comparison to ticagrelor-based 12-month dual antiplatelet therapy, ticagrelor monotherapy after 3 months of dual antiplatelet therapy caused significant reduction in a composite outcome of major bleeding and cardiovascular events at 1 year.

Disclaimer: Lupin makes no representation or warranty of any kind, expressed or implied, regarding the accuracy, adequacy, validity, reliability, availability, or completeness of any scientific information shared by the HCP on the STAR UPDATE podcast. You should not allow the contents of this to substitute for your own medical judgment, which you should exercise in evaluating the information on this website.

View Details

This secondary analysis of an open-label randomized controlled clinical trial evaluated whether low-dose triple combination antihypertensive therapy helps patients with mild to moderate hypertension to stay at target blood pressure longer than usual care.

The triple therapy combination pill contained telmisartan 20 mg, amlodipine 2.5 mg, and chlorthalidone 12.5 mg. In this triple FDC therapy versus usual care, the main endpoints were between-group differences in time at target compared over 24 weeks of follow-up, with time at target defined as percentage of time at target BP.

Almost twice as many patients receiving triple pill therapy achieved more than 50% time at target during follow-up (64% vs 37%; P < .001),

Patients in the triple therapy group had a longer time at target blood pressure than those in the usual care group (64% vs 43%; P < .001). This held true at all follow-up periods.

Triple combination antihypertensive therapy may be an effective way to control hypertension over time, and this study introduces time at target blood pressure as a novel trial outcome.

Disclaimer: Lupin makes no representation or warranty of any kind, expressed or implied, regarding the accuracy, adequacy, validity, reliability, availability, or completeness of any scientific information shared by the HCP on the STAR UPDATE podcast. You should not allow the contents of this to substitute for your own medical judgment, which you should exercise in evaluating the information on this website.

View Details

In this post hoc analysis, the frequency of occurrence of an early decline ("dip") in estimated glomerular filtration rate (eGFR) after initiation of dapagliflozin, and its association with outcomes, was evaluated in heart failure patients participated in DAPA- HF trial.

The mean change in eGFR between day 0 and 14 was -1.1 with placebo and -4.2 with dapagliflozin, giving a intergroup difference of 3.1.

Overall, 38.2% of patients — with older age, lower baseline eGFR, higher LVEF, and type 2 diabetes — experienced a >10% early decline in eGFR with dapagliflozin compared with placebo (OR, 2.36).

In the dapagliflozin group, a >10% initial decline in eGFR was associated with a 27% reduced risk of the primary outcome compared with those with a ≤10% decline (HR, 0.73).

These findings highlight that an early decline in eGFR following dapagliflozin initiation is common, small, and associated with better clinical outcomes in HF patients with rEF.

Disclaimer: Lupin makes no representation or warranty of any kind, expressed or implied, regarding the accuracy, adequacy, validity, reliability, availability, or completeness of any scientific information shared by the HCP on the STAR UPDATE podcast. You should not allow the contents of this to substitute for your own medical judgment, which you should exercise in evaluating the information on this website.

View Details

As we know, Lipoprotein(a) [Lp(a)] is an established risk factor for coronary artery disease, large artery stroke, and aortic valve stenosis.

The authors measured and genetically predicted lipoprotein(a) [Lp(a)] levels of 4, 35,579 participants from the UK Biobank to investigate the role of Lp(a) in atrial fibrillation (AF) and whether its association is independent of atherosclerotic cardiovascular disease.

Interestingly, it was found that there was a 3% increased risk of AF for every 50 nmol/L increase in Lp(a) level.

In addition, there was no evidence of a risk-conferring effect from low-density lipoprotein cholesterol and 39% of the risk-conferring effect of genetically predicted Lp(a) on AF was mediated through ischemic heart disease and aortic valve stenosis.

The main implication of these observations is the possibility that Lp(a) inhibitors can prevent AF. It is also prudent to know that aside from the recently described protective effect of finerenone, there are currently no treatments to prevent AF.

These findings suggest that elevated Lp(a) levels increase the risk of AF independent of its association with ischemic heart disease and aortic valve stenosis, although the clinical magnitude of its effect needs further characterization and validation through RCT

Disclaimer: Lupin makes no representation or warranty of any kind, expressed or implied, regarding the accuracy, adequacy, validity, reliability, availability, or completeness of any scientific information shared by the HCP on the STAR UPDATE podcast. You should not allow the contents of this to substitute for your own medical judgment, which you should exercise in evaluating the information on this website.

View Details

This post hoc analysis of the ADAPT-DES study investigated the predictors of dual antiplatelet therapy (DAPT) discontinuation, associations between different types and timing of DAPT discontinuation with thrombotic events, and the impact of on-treatment high platelet reactivity in 8582 patients who were already receiving aspirin and clopidogrel after undergoing PCI.

In result it was seen that approximately 50% of patients discontinued DAPT within 2 years, with unplanned DAPT discontinuation occurring in 16.5% of patients and discontinuation of both aspirin and clopidogrel occurring in 29.8% of patients.

Also, unplanned discontinuation was associated with a significantly increased risk of a major adverse cardiac event, with the highest risk occurring in the first 7 days after DAPT discontinuation, within 90 days of PCI, and when both antiplatelet agents were discontinued.

In this large-scale all-comers registry, premature DAPT discontinuation for unplanned reasons occurred in approximately 1 of 6 patients after DES implantation and was associated with a markedly increased risk of MACEs.

These findings suggest that unplanned DAPT discontinuation after PCI leads to worse clinical outcomes. Strategies for better identification of patients at risk for premature DAPT discontinuation are warranted to mitigate adverse outcomes.

Disclaimer: Lupin makes no representation or warranty of any kind, expressed or implied, regarding the accuracy, adequacy, validity, reliability, availability, or completeness of any scientific information shared by the HCP on the STAR UPDATE podcast. You should not allow the contents of this to substitute for your own medical judgment, which you should exercise in evaluating the information on this website.

View Details

This study compared the dementia incidence rate between users and nonusers of oral anticoagulants (OACs) in a large Australian cohort of primary care patients with atrial fibrillation.

During the mean follow‐up time of 3.7 ± 2.0 years, 425 patients had a documented diagnosis of dementia.

After propensity matching, the incidence of dementia was significantly lower in OAC users (hazard ratio [HR], 0.59; compared with nonusers.

Direct‐acting oral anticoagulant users had a lower incidence of dementia than non‐OAC users (HR, 0.49; 95% CI, 0.33–0.73; P<0.001) or warfarin users (HR, 0.46; 95% CI, 0.28–0.74; P=0.002).

No significant difference was seen between warfarin users and non‐OAC users (HR, 1.08; 95% CI, 0.70–1.70; P=0.723).

The study concluded that in patients with atrial fibrillation, direct‐acting oral anticoagulant use may result in a lower incidence of dementia compared with treatment with either warfarin or no anticoagulant.

The risk of dementia in patients with atrial fibrillation was halved in those taking a direct‐acting oral anticoagulant compared with those on warfarin. Thus, use of direct‐acting oral anticoagulants instead of warfarin in patients with atrial fibrillation may provide additional benefits by lowering the risk of dementia.

Disclaimer: Lupin makes no representation or warranty of any kind, expressed or implied, regarding the accuracy, adequacy, validity, reliability, availability, or completeness of any scientific information shared by the HCP on the STAR UPDATE podcast. You should not allow the contents of this to substitute for your own medical judgment, which you should exercise in evaluating the information on this website.

View Details

Efpeglenatide, is a novel, exendin-4-based weekly GLP-1 Receptor agonist that is administered subcutaneously, it effectively lowers glucose levels in people with T2DM.

Recent guidelines have placed this class of agents as first-line glycemic-lowering therapy in people with baseline CVD, high risk for CVD, or chronic kidney disease (CKD)

The AMPLITUDE-O Trial enrolled 4,076 adults with T2DM who had an HbA1c >7.0% and either a baseline history of CVD (89.6%) or diabetic kidney disease (DKD) with an eGFR <60 ml/min (31.6%).

Baseline CVD was defined as a history of coronary artery disease (CAD), stroke, peripheral artery disease (PAD), or if they had at least one CVD risk factor and an eGFR between 25 to 59.9 ml/min per 1.73 m2 of body surface area in adults, men age ≥50 or women ≥55.12

Notably, 21.8% of the participants had both CVD and DKD. All participants were already treated with standard of care, and they were also stratified based on the use of an SGLT-2 inhibitor (15.2%).

The primary composite outcome was the first occurrence of a 3-point major adverse cardiovascular event (MACE), including nonfatal myocardial infarction, nonfatal stroke, or death from CV-related or undetermined causes.

The key secondary outcomes were an expanded MACE composite outcome to include coronary revascularization or hospitalization for unstable angina and a composite renal outcome defined as a new onset of proteinuria (UACR > 300 mg/g) and an increase in UACR ≥ 30% from baseline, a sustained decrease of eGFR ≥ 40% for at least 30 days, a sustained eGFR < 15 ml/min per 1.73 m2 for at least 30 days, or any need for renal replacement therapy for at least 90 days.

In this pivotal CVOT, there was a 27% reduction in the primary composite outcome in participants on efpeglenatide (4 or 6 mg weekly) (HR, 0.73; 95% CI, 0.58 - 0.92; p < 0.007 for superiority) compared to placebo among persons with T2DM with CVD history or existing kidney disease

Compared to the previous CVOTs of GLP-1 RAs, the AMPLITUDE-O Trial included participants who were at a higher risk for CVD and had more cases of kidney disease

The significant benefits were also observed in the expanded MACE composite outcome, a MACE or death from non-cardiovascular causes and composite renal outcome. Benefits were greater in those who had baseline CVD, were on baseline metformin, were obese with body mass index (BMI) > 31.9 kg/m2 and had a baseline eGFR < 71.5 ml/min per 1.73 m2

This trial, with an exendin-4-based, weekly GLP-1 RA, further reinforces the expanding and robust database beyond the GLP-1 RAs that have a similar structure to human GLP-1 as powerful glycemic-lowering and weight-loss agents as well as effective in reducing CV and renal adverse event risks.

Disclaimer: Lupin makes no representation or warranty of any kind, expressed or implied, regarding the accuracy, adequacy, validity, reliability, availability, or completeness of any scientific information shared by the HCP on the STAR UPDATE podcast. You should not allow the contents of this to substitute for your own medical judgment, which you should exercise in evaluating the information on this website.

View Details

Take-Home Message No. 1

Guideline-directed medical therapy (GDMT) for HF with reduced ejection fraction (HFrEF) now includes 4 medication classes 1) renin-angiotensin system inhibition with angiotensin receptor-neprilysin inhibitors (ARNi), angiotensin-converting enzyme inhibitors (ACEi), or angiotensin (II) receptor blockers (ARB) alone; 2) beta blockers; 3) mineralocorticoid receptor antagonists (MRAs); and 4) the new group, SGLT2i

Take-Home Message No. 2

Mildly reduced LVEF has new medication recommendations, including use of SGLT2i. Weaker recommendations (COR 2b) are made for ARNi, ACEi, ARB, MRA and beta blockers in this population.

Take-Home Message No. 3

Preserved LVEF has new medication recommendations, including use of SGLT2i. New recommendations for HF with preserved EF (HFpEF) are made for SGLT2i (COR 2a), while weaker recommendation for MRAs (COR 2b), and ARNi (COR 2b).

Several previous recommendations have been renewed, including treatment of hypertension (COR 1), treatment of AF (COR 2a), use of ARB (COR 2b), and avoidance of routine use of nitrates or phosphodiesterase-5 inhibitors (COR 3: No Benefit).

Take-Home Message No. 4

Improved LVEF is used to refer to those with previous HFrEF who now have an LVEF >40%. These patients should continue their HFrEF treatment.

Take-Home Message No. 5

Value statements have been created for many treatments. In accordance with ACC/AHA methodology.High-value therapies include ARNi, ACEi, ARB, beta blocker, MRA, implantable cardioverter-defibrillator, and cardiac resynchronization therapy. Intermediate-value therapies include SGLT2i and cardiac transplantation. The only therapy identified as low value was tafamidis for cardiac amyloidosis. The value of mechanical circulatory support and pulmonary pressure monitoring was considered uncertain.

Take-Home Message No. 6

Amyloid heart disease has new recommendations for treatment. In patients with a clinical suspicion for cardiac amyloidosis, screening for serum and urine monoclonal light chains with serum and urine immunofixation electrophoresis and serum free light chains are recommended. If there is no evidence of serum or urine monoclonal light chains, bone scintigraphy is recommended to confirm the presence of transthyretin cardiac amyloidosis

Transthyretin tetramer stabilizer therapy (tafamidis) is recommended in select patients with wild-type or variant transthyretin cardiac amyloidosis. Anticoagulation is a reasonable treatment strategy to reduce the risk of stroke in patients with cardiac amyloidosis and AF.

Take-Home Message No. 7

The signs and symptoms of HF are nonspecific and thus a diagnosis of HF requires supporting evidence. Increased cardiac filling pressure is a feature of HF, and this is assumed for patients with an LVEF ≤40%. However, if the LVEF is 41% to 49% (mildly reduced) or ≥50% (preserved), evidence of spontaneous or provokable increased LV filling pressures is needed to confirm a diagnosis of HF. In such cases evidence for increased filling pressures can be obtained from non-invasive (e.g., natriuretic peptide, diastolic function on imaging) or invasive testing (e.g., hemodynamic measurement).

Disclaimer: Lupin makes no representation or warranty of any kind, expressed or implied, regarding the accuracy, adequacy, validity, reliability, availability, or completeness of any scientific information shared by the HCP on the STAR UPDATE podcast. You should not allow the contents of this to substitute for your own medical judgment, which you should exercise in evaluating the information on this website.

View Details

There is a need to identify high-risk features that predict early-onset atherosclerotic cardiovascular disease (ASCVD). The authors provide insights to help clinicians identify and address high-risk conditions in 20- to 39-year age young adults. The authors update current thinking on lipid risk factors such as triglycerides, non-high-density lipoprotein cholesterol, apolipoprotein B, or lipoprotein (a). The authors review emerging strategies, such as coronary artery calcium and polygenic risk scores in this age group, Finally, the authors discuss both the obstacles and opportunities for addressing prevention in early adulthood.

Disclaimer: Lupin makes no representation or warranty of any kind, expressed or implied, regarding the accuracy, adequacy, validity, reliability, availability, or completeness of any scientific information shared by the HCP on the STAR UPDATE podcast. You should not allow the contents of this to substitute for your own medical judgment, which you should exercise in evaluating the information on this website.

View Details

It has been controversial regarding blood pressure (BP) levels at which antihypertensive drug therapy should be started, and the adequate Blood pressure goal to be achieved following antihypertensive drug therapy in women with hypertensive disorders of pregnancy (HDP), which includes chronic hypertension (CH) as well as hypertension occurring at or after 20 weeks of gestation.

The Japan Society for the Study of Hypertension in Pregnancy (JSSHP) committee previously recommended that

● antihypertensive drug therapy should be initiated for pregnant women with severe hypertension (more than 160/110 mmHg),

● and BP should be maintained at 140–160/90–110 mmHg

However, considering the recent recommendations of other guidelines like the International Society for Study of Hypertension in Pregnancy, and National Institute for Health and Care excellence, and landmark trials like Control of Hypertension in Pregnancy Study (CHIPS) study. The Japanese committee has changed the recommendation in 2021 to following

● antihypertensive drug therapy should be used in pregnant women with severe hypertension, for whom BP levels equal to or more than 160/110 mmHg are repeatedly observed; however, it is possible to start antihypertensive drug therapy in pregnant women with BP levels that are ≥140/90 mmHg at the discretion of attending physicians

● the BP goal following antihypertensive drug therapy in pregnant women with hypertension should be <130/85

Now there have been concerns that tight control of BP in pregnancy might be associated with the occurrence of non-reassuring fetal status (NRFS) and/or fetal growth restriction (FGR).

In a meta-analysis of 45 randomized controlled trials (RCTs) including 3773 women with mild-to-moderate pregnancy hypertension, in which either placebo or antihypertensive therapy was administered to controls, the antihypertensive therapy was associated with higher incidence rates of small-for-gestational-age (SGA) infants as well as lower mean birthweight.

In another meta-analysis of RCT including 63 trials with 5909 women, the use of antihypertensive drugs had no effect on the risk of small-for-gestational-age SGA, however, in the most recent guideline of the International Society for the Study of Hypertension in Pregnancy (ISSHP), it is recommended that the target BP for antihypertensive therapy should be a DBP of 85 mmHg, regardless of the SBP. Thus warranting further studies on tight control of BP in Pregnancy and its benefit.

Dear Doctors as I sign off with this podcast series, I hope you liked my topics and podcast. Thanks for listening and wish you all good health.

Disclaimer: Lupin makes no representation or warranty of any kind, expressed or implied, regarding the accuracy, adequacy, validity, reliability, availability, or completeness of any scientific information shared by the HCP on the STAR UPDATE podcast. You should not allow the contents of this to substitute for your own medical judgment, which you should exercise in evaluating the information on this website.

View Details

Chloride is among the major electrolytes that play a unique role in fluid homeostasis and is associated with cardiorenal and neurohormonal systems.

Various HF therapies may cause hypochloremia, and hypochloremia itself can initiate and exacerbate diuretic resistance in HF.

The increasing burden of heart failure (HF) and emerging knowledge regarding chloride as a prognostic marker in HF have increased the interest in the pathophysiology and interactions of chloride abnormalities with HF-related factors and treatments.

Despite the long-standing focus of guidelines/clinicians on sodium’s role in HF, chloride is recently shown to have a more prominent contribution to the pathophysiology and prognosis of HF.

Review study has, evaluated the effects of treatment on chloride (eg, diuretic agents cause higher urinary chloride excretion and consequently serum hypochloremia), and elucidated that there are evidence for the association between chloride levels and mortality.

Disclaimer: Lupin makes no representation or warranty of any kind, expressed or implied, regarding the accuracy, adequacy, validity, reliability, availability, or completeness of any scientific information shared by the HCP on the STAR UPDATE podcast. You should not allow the contents of this to substitute for your own medical judgment, which you should exercise in evaluating the information on this website.

View Details

Tirzepatide is a dual GIP and GLP-1 receptor agonist under development for the treatment of type 2 diabetes mellitus (T2DM), obesity, and nonalcoholic steatohepatitis. Early phase trials in T2DM indicate that tirzepatide improves clinical outcomes beyond those achieved by a selective GLP-1 receptor agonist like dulaglutide

Improved glycemic control was associated with lower circulating triglycerides and lipoprotein markers and improved markers of beta-cell function and insulin resistance (IR)

In this Phase 2b trial participants were randomly assigned to receive weekly subcutaneous tirzepatide, dulaglutide, or placebo for 26 weeks. Post hoc exploratory metabolomics and lipidomics analyses were performed.

At 26 weeks, tirzepatide modulated a cluster of metabolites and lipids associated with IR, and obesity.

The decrease in metabolites like branched-chain amino acids, glutamates, branched-chain ketoacids, and indirect byproducts such as 2-hydroxybutyrate compared to baseline and placebo. were significantly larger with tirzepatide compared with dulaglutide and directly proportional to reductions of HbA1c, HOMA 2-IR indices, and proinsulin levels.

Similarly, triglycerides and diglycerides were lowered significantly compared to baseline, dulaglutide, and placebo

The study thus concluded that Tirzepatide reduces body weight and improves glycemic control and uniquely modulates metabolites associated with T2D risk and metabolic dysregulation in a direction consistent with improved metabolic health.

Disclaimer: Lupin makes no representation or warranty of any kind, expressed or implied, regarding the accuracy, adequacy, validity, reliability, availability, or completeness of any scientific information shared by the HCP on the STAR UPDATE podcast. You should not allow the contents of this to substitute for your own medical judgment, which you should exercise in evaluating the information on this website.

View Details

Systematic review and meta-analysis of 10 real-world observational studies including patients with not valvular atrial fibrillation NVAF on apixaban and rivaroxaban was done to compare the efficacy and safety of apixaban and rivaroxaban for the prevention of stroke. Surprisingly, apixaban treatment showed significantly lower hazard of 0.8 or 20% Risk reduction in stroke/systemic embolism compared to rivaroxaban.

Also, meta-analysis for a major bleeding episode was significantly lower with 38% RR with apixaban compared with rivaroxaban

The risk of Gastrointestinal bleeding was 43% lower in Apixaban compared to Rivaroxaban.

In conclusion, this study suggests that CHA2DS2-VASc and HAS-BLED scores might be an important factor when selecting oral anticoagulants.

Apixaban is associated with lower rates of both major bleeding and gastrointestinal bleeding than rivaroxaban, with no loss of efficacy.

Disclaimer: Lupin makes no representation or warranty of any kind, expressed or implied, regarding the accuracy, adequacy, validity, reliability, availability, or completeness of any scientific information shared by the HCP on the STAR UPDATE podcast. You should not allow the contents of this to substitute for your own medical judgment, which you should exercise in evaluating the information on this website.

View Details

Patients who undergo percutaneous coronary intervention (PCI) with drug-eluting stents require dual antiplatelet therapy (DAPT) for at least 6 months for stable ischemic heart disease (SIHD) or 12 months for acute coronary syndromes (ACS) to prevent stent thrombosis and other cardiovascular events (1).

The rationale for using DAPT is that aspirin and a P2Y12 antagonist (such as clopidogrel, prasugrel, or ticagrelor) separately inhibit the c (COX-1) and the adenosine diphosphate–dependent pathways, and together confer greater protection against platelet activation and stent thrombosis than either antagonist alone. Unfortunately, DAPT approximately doubles the risk of gastrointestinal (GI) bleeding compared with single antiplatelet therapy (SAPT) (2).

Mounting evidence suggests that a short course of DAPT followed by SAPT reduces bleeding without increasing ischemic events in patients with either stable ischemic heart disease (SIHD) SIHD or acute coronary syndromes ACS (3), but it is uncertain whether using either aspirin or a P2Y12 antagonist alone reduces GI injury.

To compare the separate and combined GI effects of aspirin and clopidogrel, Han et al (4) performed serial capsule endoscopy (CE) after treatment with 3 different antiplatelet regimens in patients who underwent PCI predominantly for ACS

The 3 regimen are as follows - SAPT using low-dose aspirin alone (n = 168) or clopidogrel alone (n = 169) or to DAPT using low-dose aspirin plus clopidogrel (n = 168) for an additional 6 months.

In the study , almost every patient had erosions in the stomach or small intestine on every CE study (especially the last one), and 83% of patients had some evidence of GI injury at baseline despite the fact that 39% of patients were not on antiplatelet therapy before admission but were presumably on DAPT for the 30-120 hours from PCI to the time of CE.

When the analysis focused on the subgroup of 68 patients without erosions, ulcers, or bleeding on the prerandomization CE, the investigators found that SAPT caused less GI mucosal injury (68.1% vs 95.2%; P = 0.006), including fewer new ulcers (8.5% vs 38.1%; P = 0.009), than did DAPT

The investigators found that the secondary endpoint of any type of GI bleeding between 6 and 12 months was less with SAPT compared with DAPT (0.6% vs 5.4%; P = 0.001), without an increase in ischemic events . Moreover, overt GI bleeding was 90% lower with SAPT than with DAPT relative risk [RR]: 0.10.

The other secondary outcome of clinically overt bleeding at any site, which was primarily Bleeding Academic Research Consortium 1, was also lower with SAPT than with DAPT (RR: 0.50), which was similar to the treatment effect reported in most contemporary trials evaluating SAPT after a short course of DAPT.

Disclaimer: Lupin makes no representation or warranty of any kind, expressed or implied, regarding the accuracy, adequacy, validity, reliability, availability, or completeness of any scientific information shared by the HCP on the STAR UPDATE podcast. You should not allow the contents of this to substitute for your own medical judgment, which you should exercise in evaluating the information on this website.

View Details

The 3 topic is on the top 10 messages we should know about the American College of Cardiology (ACC)/American Heart Association (AHA)/Society for Cardiovascular Angiography and Interventions 2021 coronary artery revascularization guideline

Top 10 Take-Home Messages 1. Treatment decisions regarding coronary revascularization in patients with coronary artery disease (CAD) should be based on clinical indications, regardless of sex, race, or ethnicity,

In patients being considered for coronary revascularization for whom the optimal treatment strategy is unclear, a multidisciplinary Heart Team approach is recommended.
For patients with significant left main disease, surgical revascularization is indicated to improve survival relative to that likely to be achieved with medical therapy.
Updated evidence from contemporary trials supplement older evidence with regard to mortality benefit of revascularization in patients with stable ischemic heart disease, normal left ventricular ejection fraction, and triple-vessel CAD.
The use of a radial artery as a surgical revascularization conduit is preferred versus the use of a saphenous vein conduit to bypass the second most important target vessel with significant stenosis after the left anterior descending coronary artery. Benefits include superior patency, reduced adverse cardiac events, and improved survival.
Radial artery access is recommended in patients undergoing percutaneous intervention who have acute coronary syndromes or stable ischemic heart disease, to reduce bleeding and vascular complications compared with a femoral approach.
A short duration of dual antiplatelet therapy after percutaneous revascularization in patients with stable ischemic heart disease is reasonable to reduce the risk of bleeding events..
Staged percutaneous intervention of a significantly stenosed nonculprit artery in patients presenting with an ST-segment–elevation is recommended in select patients to improve outcomes. Percutaneous intervention of the nonculprit artery at the time of primary percutaneous coronary intervention is less clear and may be considered in stable patients with uncomplicated revascularization of the culprit artery, low-complexity nonculprit artery disease, and normal renal function. In contrast, percutaneous intervention of the nonculprit artery can be harmful in patients in cardiogenic shock.
Revascularization decisions in patients with diabetes and multivessel CAD are optimized by the use of a Heart Team approach. Patients with diabetes who have triple-vessel disease should undergo surgical revascularization; percutaneous coronary intervention may be considered if they are poor candidates for surgery.
Treatment decisions for patients undergoing surgical revascularization of CAD should include the calculation of a patient’s surgical risk with the Society of Thoracic Surgeons score.

View Details

As we have seen so far Real-world studies have evaluated the use of anticoagulants in obese patients with nonvalvular atrial fibrillation (NVAF), but they have been limited by sample size or the use of diagnosis codes on claims to define obesity.

In a retrospective study of 26,522 NVAF patients with body weight of ≥100 kg or a body mass index of ≥30 kg/m2 , were enrolled from Veterans Affairs and fee-for-service Medicare system.

The study evaluated the risk of stroke/systemic embolism (SE) and major bleeding (MB) in patients that were initiated on apixaban or warfarin.

After randomization 13,604 of NVAF population were on apixaban and 12,918 were on warfarin Their mean age was 75 years, 98% male, the mean CHA2DS2-VASc score was 3.8, and the mean HAS-BLED Score was ∼2.6

It was found that apixaban patients were associated with a similar risk of stroke/ systemic embolism (hazard ratio: 0.82) and a significantly lower risk of major bleeding MB (hazard ratio: 0.62) versus warfarin.

No significant interaction was observed between treatment and obesity status for stroke/SE (p value of interaction of 0.602) or major bleeding (p value of interaction of 0.385).

The study concluded that in obese patients with NVAF, apixaban was associated with a similar risk of stroke/ systemic embolism and a significantly lower risk of major bleeding versus warfarin.

View Details

Lipoprotein (a) [Lp (a)] is associated with an increased risk of myocardial infarction, although the mechanism for this observation remains uncertain.

Objectives

A study was conducted to investigate whether Lp(a) is associated with adverse plaque progression.

Methods

In this study Lp(a) was measured in patients with advanced stable coronary artery disease undergoing coronary CT angiography at baseline and 12 months to assess progression of total, calcific, noncalcific, and low-attenuation plaque (necrotic core) in particular. High Lp(a) was defined as Lp(a) ≥ 70 mg/dL.

The relationship of Lp(a) with plaque progression was assessed using linear regression analysis.

Results

A total of 191 patients (65.9 ± 8.3 years of age; 152 [80%] male) were included in the analysis, with median Lp(a) values of 100.

At baseline, there was no difference in coronary artery disease severity or plaque burden.

Patients with high Lp(a) showed accelerated progression compared with low Lp(a) patients (P = 0.020).

Multivariable linear regression analysis confirmed the relation between Lp(a) and low-attenuation plaque volume progression (10.5% increase for each 50 mg/dL of Lp(a), 95% CI: 0.7%-20.3%).

There was no difference in total, calcific, and non-calcific plaque volume progression.

The study thus Concluded that

Among patients with advanced stable coronary artery disease, Lp(a) is associated with accelerated progression of coronary low-attenuation plaque (necrotic core).

This also explain the association between Lp(a) and the high residual risk of myocardial infarction, providing support for Lp(a) as a treatment target in atherosclerosis.

View Details

Background: EXPLORER-HCM demonstrated that mavacamten, a cardiac myosin inhibitor, improves symptoms, exercise capacity, and left ventricular outflow tract (LVOT) obstruction in patients with obstructive hypertrophic cardiomyopathy (oHCM).

Objectives: The purpose of this study was to evaluate mavacamten's effect on measures of cardiac structure and function and its association with changes in other clinical measures.

Methods: Key echocardiographic parameters from serial echocardiograms over 30 weeks were analyzed from 251 symptomatic obstructive hypertrophic cardiomyopathy (oHCM). patients out of which 123 were on mavacamten and 128 were on placebo [n = 128])

Results: More patients on mavacamten (80.9%; n = 76 of 94) vs placebo (34.0%; n = 33 of 97) showed complete resolution of mitral valve systolic anterior motion after 30 weeks (difference, 46.8%; P < 0.0001).

Mavacamten also improved measures of diastolic function vs placebo, including left atrial volume index (LAVI) (mean change from baseline of -7.5 mL/m2 [P < 0.0001) and lateral E to e' (mean change of -3.8 vs 0.04 in placebo with P < 0.0001).

Among mavacamten-treated patients, improvement in resting, Valsalva, and post-exercise LVOT gradients, Left Atrial Volume Index (LAVI), and lateral E to e' ratio was associated with reduction in N-terminal pro-B-type natriuretic peptide (P ≤ 0.03 for all). Reduction in Left Atrial Volume Index was associated with improved peak exercise oxygen consumption (P = 0.04).

Conclusions: Mavacamten significantly improved measures of left ventricular diastolic function and systolic anterior motion. Improvement in left ventricular outflow tract obstruction, Left Atrial Volume Index, and E to e' ratio was associated with reduction in a biomarker of myocardial wall stress (N-terminal pro-B-type natriuretic peptide). These findings demonstrate improvement in important markers of the pathophysiology of obstructive hypertrophic cardiomyopathy oHCM with mavacamten.

View Details

Background: The use of β-adrenergic receptor blocking agents in symptomatic patients with obstructive hypertrophic cardiomyopathy (HCM) rests on clinical experience and observational cohort studies.

Objectives: This study aimed to investigate the effects of metoprolol on left ventricular outflow tract (LVOT) obstruction, symptoms, and exercise capacity in patients with obstructive hypertrophic cardiomyopathy.

In this double-blind, placebo-controlled, randomized crossover trial 29 patients with obstructive HCM and New York Heart Association (NYHA) functional class II or higher symptoms from May 2018 to September 2020 were enrolled.

Patients received metoprolol or placebo for 2 consecutive 2-week periods in random order. The effect parameters were LVOT gradients, NYHA functional class, Canadian Cardiovascular Society (CCS) angina class, Kansas City Cardiomyopathy Questionnaire Overall Summary Score (KCCQ-OSS), and cardiopulmonary exercise testing.

Results: Compared with placebo, the LVOT gradient during metoprolol was lower at rest (25 mm Hg vs 72 mm Hg [P = 0.007),

at peak exercise it was 28 mm Hg vs 62 mm Hg [P < 0.001),

and postexercise (45 mm Hg vs 115 mm Hg [P < 0.0001).

During metoprolol treatment, 14% of patients were in NYHA functional class III or higher compared with 38% of patients receiving placebo (P < 0.01). Similarly, no patients were in Canadian Cardiovascular Society (CCS) angina class III or higher during metoprolol treatment compared with 10% during placebo treatment (P < 0.01). These findings were confirmed by higher Kansas City Cardiomyopathy Questionnaire Overall Summary Score during metoprolol treatment (P = 0.039). Measures of exercise capacity, peak oxygen consumption, and N-terminal pro-B-type natriuretic peptide did not differ between the study arms.

Conclusions: Compared with placebo, metoprolol reduced LVOT obstruction at rest and during exercise, provided symptom relief, and improved quality of life in patients with obstructive hypertrophic cardiomyopathy, while Maximum exercise capacity remained unchanged.

View Details

GIRAF trial was created with a multicenter, randomized, prospective parallel, active-controlled blinded design and conducted in 6 centers in Brazil., the trial assessed multiple cognitive outcomes in a cohort of patients randomized to 110 or 150 mg of dabigatran twice daily or once-daily warfarin.
The trial enrolled and randomized 200 patients. For inclusion in the trial, patients needed to have confirmed atrial fibrillation or atrial flutter, a CHA2DS2-VASc Score greater than 1, and be aged 70 years or older.
Exclusion criteria for the trial included a history of valvular heart disease, previous stroke, dementia or any severe neurological or psychiatric disease, major recent surgery, recent bleeding events, active cancer, warfarin contraindication, a creatinine clearance less than 30 mL/min, active liver disease, and a LVEF below 35%.
Cognitive function assessments occurred at 1- and 2-year follow-up visits. Specific function assessments used in the study included MoCA, MMSE, Geriatric Depression Scale, semantics verbal fluency, phonemic verbal fluency, Digit Symbol Substitution Test (DSST), Boston Naming Test short version, and clock-drawing test. Participants also underwent brain MRI at baseline and after 2 years to identify potential cerebrovascular events.
Upon analysis, 2-year results suggested there was less than half a point difference between the warfarin and dabigatran groups in assessments of memory, executive functions, language, and attention from baseline, but investigators noted these differences were not statistically significant. A statistically significant difference was observed for differences in MoCA score between the 2 groups, with a mean difference in change of -0.96 (with 0.02 p value of significance) favoring warfarin. Investigators also pointed out no participants were diagnosed with dementia during the follow-up period.
Thus, there was no significant difference in the majority of cognitive outcomes with warfarin or dabigatran at 2 years
Doctors, as we know Cognitive aspects are important for patients with atrial fibrillation, and these results could help guide the decision about which oral anticoagulation medication should be prescribed,”
Further studies are needed to explore new concepts on potential prevention of cognitive decline and the possible benefits of treatment for patients with atrial fibrillation and their families.”

View Details

The study randomized 1,242 patients undergoing knee arthroplasty to one of seven postoperative regimens of milvexian (25 mg, 50 mg, 100 mg, or 200 mg twice daily or 25 mg, 50 mg, or 200 mg once daily) or the anticoagulant enoxaparin (40 mg once daily). The primary efficacy outcome was venous thromboembolism, and the primary safety outcome was bleeding.
Results found that in those patients taking milvexian twice daily, venous thromboembolism developed in 21% population taking 25 mg, in 11% of the population taking 50 mg, in 9% population taking 100 mg, and in 8% of the population taking 200 mg.
Among those on the milvexian once-daily regimen, venous thromboembolism developed in 25% population taking 25 mg, in 24% population taking 50 mg, and in 7% population taking 200 mg. While in those assigned enoxaparin, venous thromboembolism occurred in 21%.
According to researchers, the dose-response relationship with twice-daily milvexian was significant (one-sided P<0.001), and the 12% incidence of venous thromboembolism with twice-daily milvexian was significantly lower than the prespecified benchmark of 30%. They also noted that bleeding rates of any severity were similar (4%) in those taking milvexian and enoxaparin. Serious adverse events were reported in 2% of patients in the milvexian group compared with 4% in the enoxaparin group.
Thus the use of the oral factor eleven (a )inhibitor, milvexian, reduced the risk of postoperative thromboembolism in patients undergoing knee arthroplasty in a dose-dependent manner without increasing bleeding risks compared with the use of a more conventional anticoagulant.

View Details

The goal of the trial was to evaluate empagliflozin compared with placebo among patients with acute decompensated heart failure. Empagliflozin is a sodium-glucose cotransporter-2 (SGLT2) inhibitor, which has been shown to reduce the risk of cardiovascular death or heart failure hospitalization among patients with chronic heart failure.

530 participants with acute heart failure were randomized to empagliflozin 10 mg daily versus placebo. Their mean age was 71 years, 47% were diabetics, and were followed for 90 days.

The participants had N-terminal pro–B-type natriuretic peptide (NT-proBNP) ≥1600 pg/ml or BNP ≥400 pg/ml during hospitalization or within 72 hours prior to admission, and the median left ventricular ejection fraction was 31%

The primary analysis showed that among patients with acute decompensated heart failure, empagliflozin versus placebo was associated with significant clinical benefit at 90 days

Empagliflozin versus placebo was also associated with fewer deaths, improvement in quality of life, and greater reduction in body weight.

Thus The EMPULSE trial showed that empagliflozin was beneficial at reducing adverse events among acute decompensated heart failure patients

View Details

The investigational PCSK9 inhibitor of Merck, MK-0616 — comes in pill form, in contrast to the three currently available PCSK9-lowering drugs that must be given in injections separated by weeks to months.

In two phase-1 studies with a total of 100 participants, MK-0616 was given daily for 2 weeks on a background of statin therapy for 14 days

The drug exhibited a dose-dependent increase in plasma exposure and > 90% mean maximum reduction of free plasma PCSK9 levels from baseline at all dose levels studied

At 14 days of treatment, participants receiving MK-0616 exhibited 65% reduction in the low-density-lipoprotein cholesterol (LDL-C)

MK-0616 was well tolerated at doses up to 300 mg with no deaths, serious adverse events, or clinically meaningful trends in laboratory safety tests, vital signs, or ECGs as a function of the study intervention.

MK-0616 represents the first oral PCSK9i with clinical data supporting its potential to be a powerful oral cholesterol-lowering agent for the treatment of hypercholesterolemia and coronary heart disease.

An oral PCSK9i would provide greater convenience and patient access and these data support further development of MK-0616 in a range of hypercholesterolemic patients.

View Details

Prolonged use of dual antiplatelet therapy (DAPT) following PCI may be associated with reduced benefits and greater harms in “real-world” clinical practice in contrast to outcomes of the DAPT Study

The study included 8,864 patients from the DAPT study and 568,540 registry patients. Longer-duration P2Y12 inhibitor therapy in the DAPT cohort was associated with a 1.01% decrease in-stent thrombosis, 1.9% decrease in major adverse cardiac and cerebrovascular events and a 2.27 decrease in MI but a 0.89% increase in moderate or severe bleeding.

The study concludes that longer-duration DAPT may have more limited benefits and greater harms when applied broadly in a contemporary real-world population, thus highlighting the need to evaluate the applicability of cardiovascular clinical trials to contemporary real-world populations more broadly.

View Details

In this trial, the safety and efficacy of bentracimab was assessed in reversing the antiplatelet effect of ticagrelor among patients needing urgent surgery or a procedure, or with major bleeding.

150 patients with a mean age of 65 years who either needed urgent surgery or a procedure or with major bleeding were enrolled in an open-label single-arm study.

On day 1, patients received an intravenous (IV) infusion of an initial IV bolus of 6 g infused over 10 minutes for rapid reversal, followed immediately by a 6 g IV loading infusion over 4 hours and then a 6 g IV maintenance infusion over 12 hours (total 18 g).

After 48 hours of follow-up, the primary reversal endpoint - minimum % inhibition of VerifyNow P2Y12 Response Unit or PRU within 4 hours of bentracimab initiation, was successfully met (p-value of significant was < 0.001).

PRUs increased from a baseline of <100 to >200 within 5-10 minutes with a steady increase by 4 hours and appeared to be sustained for 24 hours (with p-value of significance < 0.001 for all time points studied).

The results of this phase III trial indicate that bentracimab, a recombinant IgG1 monoclonal antibody antigen-binding fragment that binds with high affinity to ticagrelor and its active metabolite, is safe and effective in reversing the antiplatelet effect of ticagrelor. This drug is not expected to work against clopidogrel and prasugrel, which are irreversible P2Y12 receptor inhibitors.

Reversal was noted within 5 minutes, and the duration of reversal was infusion-time dependent. Effective haemostasis was achieved in most cases and no rebound increase in platelet activity was noted.

View Details

Direct oral anticoagulants have been evaluated in the general population, but proper evidence for their safe use in the geriatric population is lacking.

This study compared the bleeding risk of a direct oral anticoagulant (rivaroxaban) and vitamin K antagonists (VKAs) among French geriatric patients aged 80 years and above with non-valvular atrial fibrillation (AF)

In this sequential observational prospective cohort study, data from 33 geriatric centres comprised of 908 patients newly initiated on VKAs and 995 patients newly initiated on rivaroxaban.

They were followed up for up to 12 months, and risks of major, intracerebral, gastrointestinal bleedings, ischaemic stroke and all-cause mortality were compared between rivaroxaban-treated and VKA-treated patients

The study showed that 47 % RR in major bleeding and 74% RR in intracerebral bleeding in rivaroxaban-treated patients compared to VKA-treated patients

In conclusion the study indicates that bleeding risk, is lower with rivaroxaban than with VKA therapy, thus helping in stroke prevention in patients 80 years and above with non-valvular AF.

View Details

The role of diuretics in patients with intermediate-risk pulmonary embolism (PE) is controversial.

In this multicentre, double-blind trial, normotensive patients with intermediate-risk Pulmonary Embolism were randomized to receive either a single 80 mg bolus of furosemide or a placebo.

Eligible patients had at least a simplified PE Severity Index (sPESI) ≥1 with right ventricular dysfunction.

The primary efficacy endpoint assessed 24 h after randomization included (i) absence of oligo-anuria and (ii) normalization of all simplified PE Severity Index.

Safety outcomes were worsening renal function and major adverse outcomes at 48 hours defined by death, cardiac arrest, mechanical ventilation, or need of catecholamine

It was observed that the primary outcome occurred in 68/132 patients (51.5%) in the diuretic and in 49/132 (37.1%) in the placebo group with relative risk = 1.30, and significance of 0.021.

Major adverse outcome at 48 h occurred in 1 patient in the diuretic group and 4 patients in the placebo group which was non-significant.

Significant Increase in serum creatinine level was seen in diuretic than placebo group

Thus, the study concluded that in normotensive patients with intermediate-risk PE, a single bolus of furosemide improved the primary efficacy outcome at 24 h and maintained stable renal function.

In the furosemide group, urine output increased, without a demonstrable improvement in heart rate, systolic blood pressure, or arterial oxygenation.

View Details

Patients at high bleeding risk represent a prevalent subgroup among those undergoing percutaneous coronary intervention. Early aspirin discontinuation after a short course of dual antiplatelet therapy (DAPT) has emerged as a bleeding avoidance strategy.

The aim of this study was to assess the effects of ticagrelor monotherapy in reducing the incidence of primary endpoint of 2, 3, or 5 BARC bleeding after 3-month dual antiplatelet therapy in a contemporary high bleeding risk population.

Event-free patients were randomized to 12 months of aspirin or placebo in addition to ticagrelor, after 3 months of ticagrelor plus aspirin.

At the end of the study, it was observed that Ticagrelor monotherapy had reduced incidence of the primary endpoint compared with ticagrelor plus aspirin i.e. (6.3% vs. 11.4% with hazard ratio (HR) 0.53, with absolute risk differences of−2.8%.

A similar pattern was observed for more severe BARC 3 or 5 bleeding with a larger absolute risk reduction in high bleeding risk patients i. e−3.5% vs. −0.5% with significance of 0.008.

There was no significant difference in the key secondary endpoint of death, myocardial infarction, or stroke between treatment arms, irrespective of HBR status.

Thus, the study concluded that among high bleeding risk patients undergoing Percutaneous Coronary Intervention who completed 3-month DAPT without experiencing major adverse events, aspirin discontinuation followed by ticagrelor monotherapy significantly reduced bleeding without increasing ischaemic events, compared with ticagrelor plus aspirin.

The absolute risk reduction in major bleeding was larger in high bleeding risk patients than non-high bleeding risk patients.

View Details

Statin therapy has been associated with increased insulin resistance; however, its clinical implications for diabetes control among patients with diabetes is unknown.

To assess this, a large retrospective cohort study was conducted with 12 years data of 83, 022 propensity-scored matched pairs of statin users and nonusers covered by the US Department of Veterans Affairs from fiscal years 2003 to 2015.

Patients included were 30 years or older; diagnosed with diabetes during the study period; and were regular users of the Veterans Affairs health system, with records of demographic information, clinical encounters, vital signs, laboratory data, and medication usage.

Diabetes progression composite outcome comprised the following: new insulin initiation, increase in the number of glucose-lowering medication classes, incidence of 5 or more measurements of blood glucose of 200 mg/dL or greater, or a new diagnosis of ketoacidosis or uncontrolled diabetes.

Diabetes progression outcome occurred in 55.9% of statin users vs 48.0% of active comparators with odds ratio of 1.37 and significance of less than < .001.

Each individual component of the composite outcome was significantly higher among statin users. Secondary analysis demonstrated a dose-response relationship with a higher intensity of LDL-cholesterol lowering associated with greater diabetes progression.

To conclude, this retrospective matched-cohort study found that statin use was associated with diabetes progression, including greater likelihood of insulin treatment initiation, significant hyperglycaemia, acute glycaemic complications, and an increased number of prescriptions for glucose-lowering medication classes.

The risk-benefit ratio of statin use in patients with diabetes should be take into consideration by the health care professionals.

View Details

Severe coronavirus disease-2019 (COVID-19) can progress to an acute respiratory distress syndrome (ARDS), which involves alveolar infiltration by activated neutrophils. The beta-blocker metoprolol has been shown to ameliorate exacerbated inflammation in the myocardial infarction setting.

The purpose of this study was to evaluate the effects of metoprolol on alveolar inflammation and on respiratory function in patients with COVID-19-associated ARDS.

Methods:

A total of 20 COVID-19 patients with ARDS on invasive mechanical ventilation were randomized to metoprolol (15 mg daily for 3 days) or control (no treatment). All patients underwent bronchoalveolar lavage (BAL) before and after metoprolol/control. The safety of metoprolol administration was evaluated by invasive hemodynamic and electrocardiogram monitoring and echocardiography.

Results:

It was found that patients randomized to metoprolol had significantly fewer neutrophils in bronchoalveolar lavage on day 4

reduced neutrophil extracellular traps content and other markers of lung inflammation.

Oxygenation significantly improved after 3 days

And patients spent fewer days on invasive mechanical ventilation with Metoprolol therapy when compared to the control group

Thus, intravenous metoprolol administration to patients with COVID-19-associated ARDS was safe, reduced exacerbated lung inflammation, and improved oxygenation. Repurposing metoprolol for COVID-19-associated ARDS appears to be a safe and inexpensive strategy that can alleviate the burden of the COVID-19 pandemic.

•Disclaimer: Lupin makes no representation or warranty of any kind, expressed or implied, regarding the accuracy, adequacy, validity, reliability, availability, or completeness of any scientific information shared by the HCP on the STAR UPDATE podcast. You should not allow the contents of this to substitute for your own medical judgment, which you should exercise in evaluating the information on this website.

View Details

Finerenone, a selective nonsteroidal mineralocorticoid receptor antagonist, has favorable effects on cardiorenal outcomes in patients with predominantly stage 3 or 4 chronic kidney disease (CKD) with severely elevated albuminuria and type 2 diabetes.

The use of finerenone in patients with type 2 diabetes and a wider range of CKD is unclear.

In this double-blind trial, patients with CKD and type 2 diabetes were randomized to receive finerenone or placebo.

Eligible patients of stage 2 to 4 CKD had a urinary albumin-to-creatinine ratio (with albumin measured in milligrams and creatinine measured in grams) of 30 to less than 300 and an estimated glomerular filtration rate (eGFR) of 25 to 90 ml per minute per 1.73 m2 of the body-surface area or a

Eligible patients of stage 1 or 2 CKD had a urinary albumin-to-creatinine ratio of 300 to 5000 and an eGFR of at least 60 ml per minute per 1.73 m2 (stage 1 or 2 CKD).

The primary outcome, assessed in a time-to-event analysis, was a composite of death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. The first secondary outcome was a composite of kidney failure, a sustained decrease from baseline of at least 40% in the eGFR, or death from renal causes.

Results

Among 7437 patients with type 2 diabetes and stage 2 to 4 CKD with moderately elevated albuminuria or stage 1 or 2 CKD with severely elevated albuminuria, finerenone therapy improved cardiovascular outcomes by 13% with the benefit-driven primarily by a lower incidence of hospitalization for heart failure.

The first secondary outcome of kidney failure, a sustained decrease from baseline of at least 40% in the eGFR, or death from renal causes was seen numerically less with Finerenone therapy.

View Details

Background:

Even when low-density lipoprotein-cholesterol (LDL-C) levels are lower than guideline thresholds, a residual risk of atherosclerosis remains. It is unknown whether triglyceride (TG) levels are associated with subclinical atherosclerosis and vascular inflammation regardless of LDL-C.

Objectives:

This study sought to assess the association between serum TG levels and early atherosclerosis and vascular inflammation in apparently healthy individuals.

Methods:

An observational, longitudinal, and prospective cohort study, was conducted in 3,754 middle-aged individuals with low to moderate cardiovascular risk from the study group called Progression of Early Subclinical Atherosclerosis who were consecutively recruited between June 2010 and February 2014.

Peripheral atherosclerotic plaques were assessed by 2-dimensional vascular ultrasound, and coronary artery calcification (CAC) was assessed by non-contrast computed tomography, whereas vascular inflammation was assessed by fluorine-18 fluorodeoxyglucose uptake on positron emission tomography.

Results:

Atherosclerotic plaques and Coronary Artery Calcification were observed in 58.0% and 16.8% of participants, respectively, whereas vascular inflammation was evident in 46.7% of evaluated participants.

After multivariate adjustment, TG levels ≥150 mg/dl showed significant association with subclinical noncoronary atherosclerosis. This association was significant for groups with high LDL-C and normal LDL-C. No association was found between TG level and CAC score.

TG levels ≥150 mg/dl were significantly associated with the presence of arterial inflammation

Conclusions:

In individuals with low to moderate cardiovascular risk, hypertriglyceridemia was associated with subclinical atherosclerosis and vascular inflammation, even in participants with normal LDL-C levels.

View Details

Intro:

The HOPE-3 trial (Heart Outcomes Prevention Evaluation–3) found that antihypertensive therapy combined with a statin reduced the first stroke among people at intermediate cardiovascular risk.

In this study, secondary analyses of predefined stroke outcomes for each randomized intervention, was reported by stroke subtype, independent predictors, treatment effects in key subgroups, and absolute risk reductions.

Methods:

Using a 2-by-2 factorial design, 12 705 participants from 21 countries with vascular risk factors but without overt cardiovascular disease were randomized to candesartan 16 mg plus hydrochlorothiazide 12.5 mg daily or placebo and to rosuvastatin 10 mg daily or placebo. The effect of the interventions on stroke subtypes was assessed.

Results:

During 5.6 years of follow-up,

Baseline Systolic & Diastolic blood pressure (138/82 mm Hg) was reduced by 6.0 & 3.0 mm Hg and

LDL-C (low-density lipoprotein cholesterol; 3.3 mmol/L) was reduced by more than 26.5 % with Rosuvastatin.

169 strokes occurred (117 ischemic, 29 hemorrhagic, 23 undetermined).

Blood pressure-lowering by Candesartan did not significantly reduce stroke

Rosuvastatin significantly reduced the risk of the first stroke by 30% (HR, 0.70 [95% CI, 0.52–0.95]),

but did not significantly affect hemorrhagic (HR, 1.22 [95% CI, 0.59–2.54]) or

strokes of undetermined origin (HR, 1.29 [95% CI, 0.57–2.95]).

However, the combination of statin and BP-lowering lead to a substantial and significant 44% risk reduction in strokes indicating that this combination will have a large impact on the primary prevention of strokes in an average-risk population.

Results

Among people at intermediate cardiovascular risk but without overt cardiovascular disease, a low dose of rosuvastatin 10 mg daily significantly reduced the first stroke. Blood pressure-lowering combined with rosuvastatin reduced ischemic stroke by 59%.

the combination of BP lowering and statins should be considered for CVD prevention including strokes in individuals at intermediate risk. Globally this could lead to the avoidance of millions of strokes per year if these treatments were widely used.

View Details

In a Hot Line session today, Professor Steffen (Germany) presented results from the large randomized, open-label TOMAHAWK trial, which undertook to provide a definitive position on the use of early angiography in patients with shockable or non-shockable rhythm.

The trial randomized 554 patients with return of spontaneous circulation after OUT OF HOSPITAL CARDIAC ARREST with no obvious extracardiac origin of cardiac arrest and no ST-segment elevation/left bundle-branch block on post-resuscitation electrocardiogram to either immediate coronary angiography or initial intensive care unit (ICU) assessment with delayed/selective angiography in a 1:1 ratio.

The primary endpoint was all-cause mortality at 30 days.

Immediate coronary angiography did not reduce all-cause mortality, with a 30-day rate of 54% compared with 46% for delayed/selective angiography with a hazard ratio [HR] 1.28

There were no differences in the primary endpoint between the different approaches in any prespecified subgroups, including patients with shockable vs. non-shockable rhythm.

The composite secondary endpoint of all-cause death or severe neurological deficit at 30 days occurred more frequently in the immediate angiography group compared with the delayed/selective group with a relative risk of 1.16

There were no differences between immediate and delayed/selective angiography in other secondary endpoints, such as length of ICU stay, peak troponin release or myocardial infarction, or in safety endpoints, including moderate or severe bleeding, stroke, and acute renal failure requiring renal replacement therapy.

COACT was restricted to patients with shockable rhythm and TOMAHAWK extends the findings to patients with non-shockable rhythm, but both trials showed that early angiography was not superior to a delayed/selective approach.

View Details

STEP study, presented by Professor Jun Cai (Chinese Academy of Medical Sciences, Beijing, China) in a Hot Line session on 30th August.

The STEP study investigated whether intensive treatment (systolic blood pressure [SBP] target below 130 mmHg but no lower than 110 mmHg) could reduce the risk of cardiovascular (CV) events compared with standard treatment (SBP target 130–150 mmHg).

In total, 8,511 patients aged 60–80 years with SBP 140–190 mmHg during three screening visits or who were taking antihypertensive medication were randomized

The primary outcome was a composite of stroke, acute coronary syndrome (ACS), acute decompensated heart failure, coronary revascularization, atrial fibrillation, or death from CV causes.

Secondary outcomes included the individual components of the primary endpoint, death from any cause, major adverse cardiac events, and renal outcomes (a decrease in renal function or the development of end-stage renal disease)

Over a median follow-up period of 3.34 years, the mean reduction in SBP from baseline was 19.4 mmHg with intensive treatment and 10.1 mmHg with standard treatment.

Intensive treatment was associated with a 26% relative risk reduction in the number of primary outcome events compared with standard treatment

Intensive treatment was also associated with a 33% lower relative risk of stroke and a 33% lower relative risk of ACS

The incidence of safety outcomes and renal outcomes did not differ between the groups, except for hypotension, which occurred in 3.4% of patients in the intensive group and 2.6% in the standard group (p=0.03).

Thus, Active control of SBP to below 130 mmHg in older hypertensive patients, as compared with below 150 mmHg, resulted in a lower incidence of major CV events, with no increase in renal injuries.

View Details

In a Hot Line session of 28th August, Professor Marco from Switzerland presented results from the investigator-initiated, open-label MASTER DAPT trial comparing an abbreviated vs. a standard duration of antiplatelet therapy after bioresorbable polymer-coated sirolimus-eluting stent implantation in patients with acute or chronic coronary syndrome who fulfilled one or more high bleeding-risk criteria.

Following a mandatory 30-day DAPT run-in phase after percutaneous coronary intervention (PCI), eligible patients who were free from ischaemic and bleeding events were randomized 1:1 to receive abbreviated or standard DAPT.

Abbreviated treatment comprised single antiplatelet therapy until study completion, except for patients receiving clinically indicated oral anticoagulation, who continued single antiplatelet therapy up to 6 months after PCI.

Standard treatment comprised DAPT continuation for at least 5 additional months (6 months after PCI) or, for those receiving clinically indicated oral anticoagulation, for at least 2 additional months (3 months after PCI) and with continuation thereafter of single antiplatelet therapy.

The three ranked coprimary outcomes were:

1) net adverse clinical events (the composite of all-cause death, myocardial infarction [MI], stroke, and major or clinically relevant non-major bleeding);

2) major adverse cardiac and cerebrovascular events (MACCE), the composite of all-cause death, MI, and stroke)

3) major or clinically relevant non-major bleeding occurring between randomization and 335 days, defined as Bleeding Academic Research Consortium type 2, 3, or 5 bleeding.

A total of 4,579 patients from 30 countries were randomized at a median of 34 days after PCI. The mean age was 76 years, 69.3% were men, 36.2% were receiving concomitant oral anticoagulation, and 48.3% underwent PCI for the acute coronary syndrome (ACS). There was a mean of 2.1 high bleeding-risk criteria per patient.

The Abbreviated DAPT was found to be non-inferior to standard DAPT in terms of net adverse clinical events and major adverse cardiac and cerebrovascular events with. [HR] 0.97 & HR 1.02 respectively with risk difference of 0.11 percentage points

Abbreviated DAPT was superior to standard DAPT in terms of major or clinically relevant non-major bleeding events (6.5% vs. 9.4%, respectively; HR 0.68; 95% CI 0.55 to 0.84; p<0.001 for superiority), with a risk difference of −2.82 percentage points (95% CI −4.40 to –1.24).

After PCI in patients at high risk for bleeding & clinical or angiographic high ischaemic risk DAPT of 1 month can reduce bleeding risk and provide similar low post-procedural ischaemic events as standard DAPT

View Details

Results from the EMPEROR-Preserved trial were presented by Professor Stefan from Berlin in a Hot Line session on 27th August. This international double-blind trial enrolled 5,988 symptomatic HFpEF patients (LVEF >40%) with and without T2DM who had elevated N-terminal pro-BNP concentrations (>300 pg/mL in patients without and >900 pg/mL in patients with atrial fibrillation) along with evidence of structural changes in the heart or documented history of HF hospitalization.

Participants were randomized 1:1 to receive empagliflozin 10 mg daily or placebo

The primary endpoint was a composite of CV death or hospitalization for HF.

The first secondary outcome was HF hospitalizations, including first and recurrent events, while the second secondary outcome assessed the rate of decline in the estimated glomerular filtration rate (eGFR) during study treatment.

The average age of participants was 72 years, 45% were women and the average LVEF was 54%

During a median follow-up of 26 months, a primary outcome event occurred in 13.8 % of patients in the empagliflozin group and in 17.1% patients in the placebo group the hazard ratio [HR] 0.79 indicating a significant RR of 21%;

The effects on the primary outcome were observed across all prespecified subgroups, including patients with or without T2DM and those with LVEF <50%, 50 to <60%, or >=60%.

The secondary outcomes, the total number of HF hospitalizations was lower with empagliflozin than with placebo (HR 0.73; indicating significant RR of 27 %. Furthermore, the rate of eGFR decline was slower with empagliflozin than placebo

Regarding safety, serious adverse events occurred in 47.9% of patients in the empagliflozin group and 51.6% in the placebo group. Adverse events leading to discontinuation of treatment occurred in 19.1% of patients in the empagliflozin group and 18.4% in the placebo group. Uncomplicated genital and urinary tract infections and hypotension were more common in patients treated with empagliflozin.

Empagliflozin convincingly reduced the combined risk of CV death or hospitalization for HF in patients with HFpEF with and without T2DM.

EMPEROR-Pooled analysis, which pooled individual patient data from EMPEROR-Reduced and EMPEROR-Preserved found that in 9,718 patients included in the analysis, empagliflozin reduced the risk of HF hospitalization to a similar degree (about 30% risk reduction) in EMPEROR-Preserved and in EMPEROR-Reduced. The magnitude of the effect on HF hospitalizations was similar across a broad range of ejection fractions lower than 65%, with attenuation of the drug effect at higher ejection fractions (≥65%).

The analysis also found that empagliflozin reduced the risk of major renal outcomes in EMPEROR-Reduced, but not in EMPEROR-Preserved

View Details

This is a post hoc analysis of the ARIC study, with the objective to assess the association of diabetes duration with incident heart failure (HF).

In this study, 9,734 participants from the ARIC study with mean age of 63 years without HF or coronary heart disease were included and their diabetes duration at Visit 4 was taken as baseline.

After 22.5 years of follow up, it was found that,

Each 5-year increase in diabetes duration was associated with a 17% (95% CI: 11-22) relative increase in HF risk.
The HF and diabetes duration associations were stronger among those aged <65 years, those with HbA1C ≥7%, those with a body mass index ≥30 kg/m2, women, and Blacks (all P interactions <0.05).
Among the 168 study subjects (2% of the total study group) who had diabetes for at least 15 years, the subsequent incidence of heart failure was nearly threefold higher than among the 4,802 subjects (49% of the total study group) who never had diabetes or prediabetes.
People with prediabetes (32% of the study population) had a significant but modest increased rate of incident heart failure that was 16% higher than in control subjects who never developed diabetes.
People with diabetes for durations of 0-4.9 years, 5.0-9.9 years, or 10-14.9 years, had steadily increasing relative incident heart failure rates of 29%, 97%, and 210%, respectively, compared with controls.
The rate of incident heart failure with reduced ejection fraction (HFrEF) roughly matched the rate of incident heart failure with preserved ejection fraction (HFpEF).

Thus this analysis concluded that,

Delaying diabetes onset may augment HF prevention efforts, and therapies to improve HF outcomes might target those with long diabetes duration.

View Details

This study was aimed to evaluate if a shorter course of Dual Anti-Platelet Therapy followed by P2Y12 inhibitor monotherapy is as effective as a 12-month course with fewer bleeding events.

Five randomized clinical trials were included, with a total of 18,046 participants.

Antiplatelet strategies compared were

· aspirin and P2Y12 inhibitor for 12 months

· aspirin and P2Y12 inhibitor for 1 to 3 months followed by P2Y12 inhibitor alone.

In the end of the study it was found that Patients randomized to 1 to 3 months of DAPT followed by P2Y12 inhibitor monotherapy had statistically significant lower rates of major bleeding (1.42% vs 2.53%; OR 0.53; 95% CI 0.42-0.67; p < 0.001; I2 = 0%) and

Also significant reduction in all-cause mortality (1.00% vs 1.42%; OR 0.71; 95% CI 0.53-0.95; p = 0.02; I2=0%) with similar major adverse cardiac events (MACE) (2.66% vs 3.11%; OR 0.86; 95% CI 0.71 – 1.03; p = 0.10; I2 = 0 %) compared to 12 months of DAPT.

The study concluded, that a shorter course of DAPT for 1 to 3 months followed by P2Y12 inhibitor monotherapy reduces major bleeding and all course mortality without increasing major adverse cardiac events compared with traditional DAPT for 12 months.

View Details

Background: Patients with peripheral artery disease (PAD) undergoing Lower extremity revascularization (LER) are at high risk of major adverse limb and cardiovascular events.

The VOYAGER PAD trial demonstrated that rivaroxaban 2.5 mg twice daily reduced first events by 15%. The benefit of rivaroxaban on total (first and subsequent) events in this population are unknown.

The Objectives: of this study sought to evaluate the total burden of vascular events in patients with PAD after Lower extremity revascularization and the efficacy of low-dose rivaroxaban on total events.

Methods: In this study patients with PAD undergoing Lower extremity revascularization were randomized to rivaroxaban 2.5 mg twice daily plus aspirin or aspirin alone.

The primary endpoint was time to the first event of acute limb ischemia, major amputation of a vascular cause, myocardial infarction, ischemic stroke, or cardiovascular death.

The current analysis considered all events (first and subsequent) for components of the primary endpoint as well as additional vascular events including peripheral revascularizations and venous thromboembolism.

As Results: Rivaroxaban significantly reduced total primary endpoint events and total vascular events by (HR: 0.86; 95% CI: 0.75-0.98; P = 0.02) & (HR: 0.86; 95% CI: 0.79-0.95; P = 0.003) respectively.

An estimated 4.4 primary and 12.5 vascular events per 100 participants were avoided with rivaroxaban over 3 years.

Conclusions: Patients with PAD undergoing Lower extremity revascularization are at high risk of adverse limb and cardiovascular events, with a particularly high burden when considering total events in spite of standard available medical therapy.

The risk profile in patients with symptomatic PAD is dominantly driven by adverse limb outcomes, particularly after Lower extremity revascularization, including acute limb ischemia, major vascular amputation, and recurrent revascularization.

Rivaroxaban 2.5 mg twice daily with aspirin versus aspirin alone reduces first and subsequent adverse limb and cardiovascular events with an even greater total benefit when considering all events.

View Details

Efficacy and Safety of Antithrombotic Strategies in Patients with Atrial Fibrillation and Recent ACS or PCI With and Without A History of Heart Failure: Insights From the AUGUSTUS Trial

The Augustus trial was done in AF patients with recent ACS or PCI, and Apixaban on the background of P2Y12 without aspirin resulted in less bleeding, few hospitalization,s and no significant difference in ischemic events compared to a regimen that included a Vitamin K Antagonist, aspirin or both.

Heart Failure is frequent in this population due to a prothrombotic state and is associated with high mortality and morbidity.

In this study, they evaluated the safety and efficacy of 2 different antithrombotic regimens in patients with or without Heart Failure irrespective of ejection fraction. 4614 patients with background P2Y12 therapy were randomized to either Apixaban or VKA regimen and each group was re-randomized to aspirin or placebo.

At end of 6 months, the results showed that the patient group with Heart Failure had higher Cardiovascular death and All-cause death events compared to the group without Heart Failure, while the risk of major bleeding, all-cause death or hospitalization, or all-cause death or ischemic event remained fairly same between the group.

Comparison between Apixaban and VKA therapy in patients with HF showed no significant difference in terms of major bleeding, all-cause mortality or hospitalization, or all-cause death or ischemic event. Similarly, Aspirin therapy in patients with Heart failure increases major bleeding events but remained statistically non-significant like the rest of the adverse events.

Thus the study concluded that a history of Heart Failure is common in patients with AF and in recent ACS or PCI and also associated with an increased risk for all-cause and CV mortality.

Irrespective of history of HF, treatment with P2Y12 and an antithrombotic regimen that included apixaban without aspirin resulted in less major or clinically relevant non-major bleeding and fewer death and hospitalizations than regimen that included a vitamin K antagonist, aspirin, or both.

View Details

AFFIRM-AHF-based multinational cost-effectiveness analysis of intravenous ferric carboxymaltose for the treatment of iron deficiency in an acute heart failure setting

Heart Failure utilizes major resources and is an economic burden on healthcare systems.

Iron deficiency is prevalent in 50% of patients with chronic HF and in 80% of patients hospitalized for acute HF. It is associated with poor functional status and increased risk of adverse outcomes in HF patients, thus Iron deficiency in HF is an area of significant unmet need.

In the AFFIRM-AHF trial, patients hospitalized for acute HF with LVEF <50%, having iron deficiency and Hb level between 8-15g/dl were randomized to either placebo or Ferric Carboxy maltose (FCM) and followed periodically for 52 weeks. The primary outcome was a composite of HHF and CV death, and Secondary outcomes were total HF hospitalization, CV death, and most importantly change from baseline in Kansas City Cardiomyopathy Questionnaire – Clinical Summary Score (KCCQ-CSS).

The outcome analysis showed that the Primary composite Endpoint was not met with a significance value of less than 5%.

But the total HF hospitalization events were significantly reduced with p-value of 0.013 and a risk reduction of 11 events per 100 patient years.

The KCCQ-CSS score at baseline was 40, and significant improvement was seen between the 4th and 24 weeks compared to the placebo.

View Details

Vericiguat in patients with atrial fibrillation and heart failure with reduced ejection fraction: Insights from the VICTORIA (VerICiguaT global study in subjects with HFrEF)

As we know, Heart failure is associated with impaired synthesis of Nitric Oxide and decreased activity of soluble Guanylate Cyclase (sGC), which may contribute to myocardial and vascular dysfunction. By directly stimulating soluble Guanylate Cyclase, independently of and synergistically with Nitric Oxide, Vericiguat augments levels of intracellular cGMP, leading to smooth muscle relaxation and vasodilation.

AF is a common arrhythmia involved with Heart Failure and complicating factor for HF with reduced ejection fraction. The effect of some guideline-based treatments may differ according to whether AF is present or not. In the VICTORIA trial, 45% had HF with Atrial fibrillation and the objective was to determine the relationship of AF with outcomes of Vericiguat treatment.

The trial also assessed the occurrence of new-onset AF post-randomization

The result showed that there was no association of AF with Primary outcomes, CV death, and Hospitalization for Heart Failure in patients on Vericiguat treatment.

Over median follow-up of 10 months, new-onset AF was seen in 10%, among them, 6% has no prior AF and 18% has intermittent AF. The incidence of new-onset AF did not differ among patients receiving placebo and Vericiguat.

Thus the study concluded that nearly half of patients with HF with reduced ejection fraction and decompensated Heart Failure had Atrial Fibrillation. Patients with intermittent AF had worse outcomes with new onset of AF in less than a year. The beneficial effect of Vericiguat was unaffected by any of AF at baseline.

View Details

Efficacy of Omecamtiv mecabril in heart failure with reduced ejection fraction according to N-terminal pro-B-type natriuretic peptide level: Insights from the GALACTIC-HF trial.

The primary outcome of this trial was the time to first heart failure event or cardiovascular death, which occurred significantly less in patients randomized to Omecamtiv mecabril group.

In sub-analysis, the effect of Omecamtiv mecarbril on NT-pro BNP level, and pre-specified outcomes based on NT-pro BNP level i.e. < or > median value i.e. 1675 pg/ml, and on continuous NT-pro BNP level were also evaluated

The result showed that Omecamtiv Mecarbril reduced NT-pro BNP levels more in patient with NT-pro BNP above-median than those with levels below the median

The pre-specified outcome results showed that those with NT-pro BNP level above the median had higher event rates compared to those below the median. Those who were randomized to Omecamtiv Mecarbril had lower event rate compared to placebo, with higher risk reduction in those with NT-pro BNP level above the median, compared to those below median.

If we look at continuous NT-pro BNP levels, the Omecamtiv Mecarbril arm had significant risk reduction at higher NT-pro BNP levels

With this, the study concluded that baseline NT-pro BNP level modifies the treatment outcomes with Omecamtiv Mecarbril in HF patients without AF/F. The investigated drug greatly reduced NT-pro BNP level in those with above-median level of the marker, thus consistent to other analysis from Galactic-HF, this study suggests that Omecamtiv Mecabril has a greater benefit in patients with more severe Heart Failure with reduced ejection fraction.

Disclaimer: Lupin makes no representation or warranty of any kind, expressed or implied, regarding the accuracy, adequacy, validity, reliability, availability or completeness of any scientific information shared by the HCP on the STAR UPDATE podcast. You should not allow the contents of this to substitute for your own medical judgment, which you should exercise in evaluating the information on this website.

View Details

What is the evidence and which beta-blocker should a patient with HFmrEF receive?

Till Copernicus trial ejection fraction were used to define outcome of a trial, but now this clinical parameter is used to group individuals with Heart Failure that will yield different outcome to a given treatment.

In 2016, ESC Heart Failure guidelines classified and defined HF with reduced ejection fraction, HF with preserved ejection fraction, and HF with mid-range ejection fraction.

Studies like CHARM, I PRESERVE & TOPCAT were disappointment as they showed results with ARNI or RAAS inhibitors close to placebo in patients with HF with preserved ejection fraction, only PRAGON-HF trial with Sacubitril/Valsartan showed a positive response.

In post hoc analysis of CHARM study, Candesartan treatment showed effectiveness in HF with reserved and mid-range ejection fraction and not in preserved ejection fraction.

If we consider retrospective studies with Beta Blockers, in SENIORS trial among all type of HF patient, individuals with mid-range ejection fraction were also fairly represented, and the outcomes showed less mortality & CV hospitalization in patients with LVEF >35%. When further analysis were made with LVEF in quintiles, it was revealed that those in >40-60% had significant mortality and hospitality benefit compared to other quintiles.

A meta-analysis of Beta Blockers in Heart Failure showed significant survival from all-cause mortality & CV mortality in patients with LVEF 40-49% with sinus rhythm.

Thus it was concluded that post ESC HF guidelines we have more knowledge of outcomes of HF with mid-range ejection fraction, more retrospective evidence, the best evidence of outcome is with Beta Blockers and with Sacubitril + Valsartan from studies with particular data on mid-range Heart failure.

Thus we can treat mid-range HF effectively.

View Details

The goal of the trial was to assess the efficacy and safety of sacubitril/valsartan compared with ramipril in a contemporary acute myocardial infarction (AMI)

IN THIS,

5,660 PATIENTS FROM 43 COUNTRIES

WITH MEAN AGE OF 64 YEARS

WITH PRIOR MI

WITH Left ventricular ejection fraction ≤40% with or without pulmonary congestion

WERE RANDOMIZED TO RECEIVE EITHER sacubitril/valsartan OR RAMIPRIL AND WERE FOLLOWED UP FOR 23 MONTHS.

THE RESULT OF THE TRIAL SHOWED THAT,

The primary outcomes of CV death or HF hospitalization were not statistically different between the groups.

In the secondary outcomes, the composite endpoint of all Heart Failure events & mortality showed a significance of 0.02

No major adverse events were seen either in both arms.

Interestingly, although the events were numerically lower, the trial did not reach its statistical target to show the clinical benefit of sacubitril/valsartan over standard Ramipril in post-MI patients.

View Details

In this trial, 15,000 patients from 40 centers across the U.S. were self-enrolled and self-randomized between 2016 & 2019.

The Participants were of median age of 67 years

With 35.3% had a history of myocardial infarction (MI) and

53% had coronary revascularization within the previous five years.

The Results showed after median 26 months of follow-up were as follows

No significant difference in the primary effective outcome of all-cause death, MI, or stroke OR

Primary safety outcome of major bleeding requiring blood transfusion at 12 months.

But there was a high rate of dose switching and discontinuation in patients on a higher dose of Aspirin.

Thus this study is very illustrative of fact that low dose Aspirin is equally effective as high dose, and the switch over and discontinuation may be due to GI.

View Details

The goal of the trial was to assess the efficacy and safety of Apixaban 5 mg BID compared with standard of care (antiplatelet therapy [APT] or oral anticoagulant [OAC]) among patients undergoing transcatheter aortic valve replacement commonly known as (TAVR).

In this study 1500 patients of mean age of 82 years, with 53% having a Self-expanding valve; 47% with balloon-expandable valve and 3% with valve-in-valve were included.

The trial was divided into 2 layers, in one stratum Apixaban was compared to standard Vitamin K Antagonist requiring Oral Anti-Coagulant therapy and in other stratum Apixaban was compared to standard Antiplatelet therapy (Single or Dual) not requiring an Anti-Coagulant therapy.

The results after a median follow up of 1 year showed that

The composite primary endpoint of time to death, stroke, myocardial infarction (MI), systemic emboli, intracardiac or valve thrombosis, deep vein thrombosis/pulmonary embolism, or major bleeding between Apixaban and standard of care with Vitamin K Antagonist or DAPT/SAPT was not statistically significant. Similar results were also seen with Primary safety outcomes.

In the secondary outcome of all-cause mortality, death, MI and stroke was higher in the Apixaban group

The major bleeding events were more in Apixaban compared to standard of care

Non-cardiovascular death was higher with Apixaban in patients that did not require anti-coagulation therapy.

The venous thromboembolism was significantly lower in the Apixaban treatment arm compared to standard of care, this was also confirmed with subset 4D-CT imaging analysis

The results of this trial indicate that apixaban is not superior to the standard of care among patients undergoing TAVR.

Valve leaflet thrombosis was lower with apixaban compared with Anti-Platelet Therapy, but this did not translate into an improvement in clinical outcomes.

In fact, among patients without an indication for OAC, apixaban use resulted in higher noncardiovascular mortality compared with APT use.

Results are similar to the GALILEO trial with low-dose rivaroxaban. These data do, however, support the use of apixaban instead of VKA if needed among patients requiring long-term OAC.

View Details

The goal of the trial was to evaluate surgical left atrial appendage occlusion compared with no occlusion among patients with atrial fibrillation undergoing open-heart surgery.

In this trial, 4770 patients on anticoagulation therapy for over 3 years with atrial fibrillation with CHA2DS2-VASc ≥2, were randomized to undergo open-heart surgery with or without left atrial appendage occlusion

In results:

The primary outcome of ischemic stroke or systemic embolism after 3.8 years occurred in 4.8% of the occlusion group compared with 7.0% of the no occlusion group with a significance of 0.001

In the Secondary outcomes, the event of Ischemic stroke was also significantly lesser to the non-occlusion arm.

Among patients with atrial fibrillation undergoing cardiac surgery, left atrial appendage occlusion was found to be superior to no occlusion.

More benefit was observed when the results were landmarked at 30 days versus <30 days.

Major bleeding was similar between the treatment groups.

Thus to conclude the benefit of surgical left atrial appendage occlusion appeared to be additive to anticoagulation therapy; therefore, this trial does not support surgical left atrial appendage occlusion as a replacement to anticoagulation therapy.

View Details

Studies have shown that patient with COVID-19 and underlying Cardiovascular disease were more likely to show raised cardiac Troponin-T and have a 70% risk of poor prognosis or early mortality, further data suggest that level of cardio biomarkers like myoglobin, NT-pro BNP was significantly higher in severe & critical cases versus mild cases. It was known that in Covid infections, cardiac morbidities like Myocarditis, Hypertensive crisis, CHF, and Myocardial infarction can cause marked elevation of Troponin T.

Thus it is can be concluded that Level of Troponin-T can help us in risk stratification, prognostication, and categorization of Covid cases.

In March 2020, the European Society of Cardiology and American College of Cardiology has recommended measuring cTnT only if the diagnosis of MI is being considered on clinical grounds or if there is new onset of LV dysfunction.

View Details

Recently a meta-analysis was conducted on 7 randomized controlled trials of PCI or CABG plus Optimal Medical Therapy (OMT) versus OMT alone involving 10797 patients with chronic coronary syndromes

This is the first meta‐analysis to include patients with CCS and severely reduced left ventricular ejection fraction as well as those with CKD. This is the only meta‐analysis with documented myocardial ischemia and in which revascularization included both PCI and CABG.

After a follow-up of 5 years, it was found that initial revascularization with PCI or CABG plus OMT did not reduce long‐term mortality compared with OMT alone. In subgroup analysis, CABG plus OMT reduced non-fatal MI and not PCI plus OMT, in comparison to OMT alone therapy.

Thus it can be concluded that in patients with only chronic coronary syndrome, the decision of revascularization should be based on discussions of symptom relief and quality of life and not about a reduction in mortality. Secondly, for patients in whom reduction in MI is an overarching goal, such as those with severely reduced left ventricular ejection fraction, CABG plus optimal medical therapy is superior to OMT and PCI plus OMT.

View Details

Triple combination therapy, either initial or sequential is part of the recommendation in the ESC/ERS guidelines for the treatment of Pulmonary Arterial Hypertension (PAH). OPUS is a prospective, multicenter, observational drug registry of PAH patients newly initiated on macitentan. Recently, analysis was done on treatment patterns, outcomes, and safety for PAH patients receiving triple combination therapy comprising of macitentan plus a phosphodiesterase type 5 inhibitor (PDE5i) plus a prostacyclin pathway agent (any route) in OPUS from April 2014 to 2020.

In the study triple therapy was either initial (i.e. with no PAH therapy for over 60 days before the start of triple therapy) or sequential (i.e. with ≥1 PAH therapy for over 60 days from the start of triple therapy). In the registry 51 (12.6%) patients were on initial triple therapy and 353 (87.4%) patients were in sequential therapy.

Change in clinical characteristics was seen better in the initial triple therapy group with improvement in 6min walking distance, Functional Class, NT pro-BNP, and BNP compared to sequential therapy group. From a safety point of view, no change in the Hepatic adverse event was seen among the triple therapies with Macitentan, but drug discontinuation (Prostacyclin) was seen more with initial triple therapy than with sequential.

Kaplan-Meier (KM) estimates (95% CI) patients in Macitentan initiation showed that 69% (for mono), 62% (double) and 61% (triple) therapy were free from hospitalization at 12 months. Survival after 1 year was seen in 91% (sequential), 78% (initial) triple therapy patients.

Thus to conclude, there is a steady increase in triple therapy for patients with PAH, and a large improvement in clinical status was seen. The observed safety profile indicates that the majority of patients tolerate this triple regimen with Macitentan.

View Details

Aspirin is an affordable, familiar, and most widely prescribed drug for acute and post cardiovascular events or revascularization procedures. It is also an essential member of dual antiplatelet therapy or DAPT (a P2Y12 inhibitor plus ASA) and dual pathway inhibition or DPI (Rivaroxaban plus ASA), and data for both combinations are increasing.

Gastrointestinal bleeding is the most common adverse event associated with Aspirin therapy, the COGENT trial has shown that prophylactic PPI agents reduced this risk in Clopidogrel plus Aspirin DAPT therapy. Recently, phospholipid-coated formulation of ASA has been studied in comparison to regular uncoated ASA, the analysis suggests a faster antiplatelet effect, and the endoscopic evaluation has shown decreased ulceration. Further studies are necessary for fewer GI bleeding events and better adherence.

Other novel formulations of ASA as inhaled nanoparticle was developed to enhance the speed of platelet inhibition and avoid gastric effects by evading GI and hepatic metabolism. In its Phase 1 study, the nanoparticle ASA formulation showed good sustained-release kinetics, increased anti-inflammatory properties, and faster platelet inhibition compared to regular chewing and swallowing of ASA.

Thus, it is evident that as the role of Aspirin as monotherapy or DAP / DPI therapy is reappraised, newer formulations are developed to enhance the utility of this drug for its bright future.

Star Update Podcast - Cardiology News Summaries: Recent Episodes

ImagicaHealth