Is mavacamten superior to aficamten for hypertrophic cardiomyopathy? A frequentist network meta-analysis

Background: Myosin inhibitors have been shown to improve exercise capacity and symptoms, as well as reduce the left ventricular outflow tract (LVOT) gradient. This study explores the efficacy of mavacamten versus aficamten in hypertrophic cardiomyopathy (HCM) patients. Methods: From the inception to October 2024, the electronic databases [Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, and ClinicalTrials.gov] were searched. Using a random-effects model and a frequentist framework, specific effect sizes [mean difference (MD) and risk ratio (RR)] were pooled. Results: This network meta-analysis included six randomized controlled trials (RCTs). A total of 826 individuals with HCM were included; 443 of them received a cardiac myosin inhibitor, while 383 received placebo. Comparison of aficamten versus mavacamten through a common comparator, placebo, showed that aficamten caused a lesser decrease in resting LVOT gradient than that of mavacamten [MD = 14.74, 95% CI (3.02; 26.47)]. Therefore, mavacamten ranked higher (P-score = 0.9966) than aficamten (P-score = 0.5034) in decreasing resting LVOT gradient. Aficamten significantly reduced left ventricular ejection fraction (LVEF) in contrast to mavacamten [MD = –5.59, 95% CI (–10.43; –0.75)]. According to P-score ranking, mavacamten (0.5053) ranked higher than aficamten (0.0059). For New York Heart Association (NYHA) class improvement, there was no statistically significant difference between the two groups [MD = –0.37, 95% CI (–1.79; 1.06)]. But P-score ranked mavacamten (0.8466) higher than aficamten (0.6533). Discussion: Mavacamten ranked superior to aficamten in HCM management. However, this ranking is based not on the absolute clinical benefit but on the network point estimates. Additionally, due to a larger body of clinical evidence supporting mavacamten, it has a clear advantage in terms of reliability. Therefore, more direct trials comparing the two drugs would be required to confirm which one is better and provide conclusive evidence.