Cardiac myosin inhibitors mavacamten and aficamten demonstrate short-term safety and efficacy in reducing left ventricular outflow tract obstruction and improving functional capacity in HCM.
Do cardiac myosin inhibitors (mavacamten and aficamten) improve outcomes in patients with hypertrophic cardiomyopathy?
Cardiac myosin inhibitors (mavacamten and aficamten) represent a paradigm shift in HCM management with proven short-term safety and efficacy, though long-term data are still needed.
Hypertrophic cardiomyopathy (HCM) is the most common monogenic heart disease, with an estimated prevalence of 1:600 in the general population, and is associated with significant morbidity. HCM is characterized by left ventricular hypertrophy and interventricular septal thickening due to sarcomere protein gene mutations. The recent emergence of cardiac myosin inhibitors (CMIs), specifically mavacamten and aficamten, has introduced a paradigm shift in HCM management by directly targeting the hypercontractile state of the disease. This review comprehensively discusses the molecular mechanisms of mavacamten and aficamten, highlighting their biochemical similarities and differences from available data. It evaluates their reported efficacy in completed clinical trials, such as reducing left ventricular outflow tract (LVOT) obstruction, improving functional capacity, and enhancing quality of life in HCM. It further provides insight and updates to ongoing trials of both CMIs. Finally, it compares and elaborates on the safety profiles of mavacamten and aficamten, discussing their favorable safety profiles shown in completed studies. In current clinical practice, only mavacamten is approved for use, and clinical insights concerning both CMIs are limited, but encouraging. In summary, cardiac myosin inhibitors are a promising class of disease-modifying drugs for HCM with proven short-term safety and efficacy, but limited data are available to fully determine their long-term effects and efficacy in diverse patient populations. Ongoing research is necessary to further explore and define their role in HCM management.
Savsin et al. (Tue,) conducted a review in Hypertrophic cardiomyopathy (HCM). Cardiac myosin inhibitors (mavacamten and aficamten) was evaluated. Cardiac myosin inhibitors mavacamten and aficamten demonstrate short-term safety and efficacy in reducing left ventricular outflow tract obstruction and improving functional capacity in HCM.