To the Editor In a recent randomized clinical trial, Dr Nissen and colleagues found that lepodisiran, an extended-duration short interfering RNA targeting lipoprotein(a), demonstrated high tolerability while decreasing serum lipoprotein(a) concentrations in a dose-dependent way over an extended period. These results were unexpected, necessitating a cautious approach to their interpretation. A significant concern is the potential for long-term toxicities due to the persistent therapeutic effects after a single dose.