Comparative Efficacy of Mavacamten versus Aficamten in Hypertrophic Cardiomyopathy: A Systematic Review and Network Meta-Analysis

Abstract

Objectives: Sarcomere-targeted treatments improve functionality in individuals with Hypertrophic cardiomyopathy (HCM), which can be fatal with significant morbidity, by lowering LVOT gradients. Methodology: From the inception to October 2024, the Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, and ClinicalTrials.gov were the electronic databases that were searched. A frequentist framework was employed using R software for statistical analyses, and the random-effects model was used to pool study-specific effect sizes (mean difference and risk ratios). Results: Six RCTs were included in our meta-analysis. With a mean age ± SD of up to 59.8 ± 14.2 years in intervention against 60.9 ± 10.5 years in placebo, 826 individuals with hypertrophic cardiomyopathy were included; 443 of them received cardiac myosin inhibitor, while 383 received a placebo. When compared to Mavacamten through an indirect comparison, Aficamten (MD = 14.74, 95% CI [3.02; 26.47]) significantly altered the resting LVOT gradient, however Mavacamten ranked higher (P-score= 0.9966) than that of Aficamten (P-score=0.5034) in decreasing resting LVOT gradient. Aficamten significantly reduced LVEF in contrast to Mavacamten (MD = -5.59, 95% CI [-10.43; -0.75]). According to the P-score ranking, Mavacamten (0.5053) was superior to Aficamten (0.0059), while placebo (0.9887) ranked the highest when decrease in LVEF was considered undesirable. For 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). Conclusion: Mavacamten ranked superior to Aficamten as a treatment option in decreasing LVOT gradient, decreasing LVEF and NYHA class improvement when compared indirectly for HCM management. However, due to larger body of clinical evidence supporting Mavacamten, it has a clear advantage in terms of reliability, safety, and efficacy. Therefore, more direct trials comparing the two drugs would be required to confirm if one is better than the other.