Mavacamten and Aficamten in Hypertrophic Cardiomyopathy: A Systematic Review and Meta-Analysis of Randomized Trials

Clinical Snapshot

Key Findings

• P Value: Not reported in abstract

• Effect Size: Generally larger effect magnitudes with mavacamten compared to aficamten

• Primary Outcome: Improvement in NYHA functional class and KCCQ-CSS for both agents

• Nnt Or Sensitivity: Not calculable from available data

• Confidence Interval: Not reported in abstract

Clinical Application

Both agents require specialist cardiology oversight and regular monitoring; mavacamten available through PBS Special Authority Mavacamten approved by TGA and available via PBS for eligible HCM patients; aficamten approval status unclear; specialist HCM centres available in major cities Adults with symptomatic hypertrophic cardiomyopathy and LVOT obstruction

Abstract

Myosin inhibitors represent a novel therapeutic class for hypertrophic cardiomyopathy (HCM). While both mavacamten and aficamten have been evaluated in randomized trials, comparative evidence across the 2 agents remains limited. We performed a systematic review and meta-analysis of 8 randomized controlled trials of myosin inhibitors in HCM. Outcomes included improvement in the New York Heart Association (NYHA) functional class, Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CSS), postexercise and resting left ventricular outflow tract (LVOT) gradients, mean rest LVOT peak gradient, mean Valsalva LVOT peak gradient, change in left ventricular ejection fraction (LVEF), peak oxygen uptake, N-terminal pro-B-type natriuretic peptide (NT-proBNP), treatment-emergent adverse events, and serious adverse events. Pooled effects were estimated twice using random-effects models, once stratified by drug and once pooled altogether. Results showed that myosin inhibitors improved clinical and hemodynamic outcomes versus placebo. Both mavacamten and aficamten yielded improvements in New York Heart Association functional class and KCCQ-CSS, while reducing LVOT gradients and proBNP levels. Effect magnitudes were generally larger with mavacamten; aficamten demonstrated concordant but smaller effects and was the only agent to increase peak oxygen uptake. Safety was favorable for both agents, with pooled estimates indicating a marginally more favorable safety profile for aficamten. In conclusion, myosin inhibitors improve functional status, quality of life, and hemodynamics in HCM with an acceptable safety profile. Mavacamten generally demonstrates more robust benefits, while aficamten appears to have a more favorable safety profile. Additional trials directly comparing these agents are warranted to better clarify relative efficacy and safety.

References

1. 1.Fahim, M. D., Eldawud, D., Wahadneh, O., Wang, R., Gorantla, A., Sharma, N., Khouri, P., & Salciccioli, L. (2026). Mavacamten and aficamten in hypertrophic cardiomyopathy: A systematic review and meta-analysis of randomized trials. The American Journal of Cardiology. https://doi.org/10.1016/j.amjcard.2026.02.018