Mavacamten improved NYHA class in obstructive HCM (OR 4.94; 95% CI 3.25-7.49), but in non-obstructive HCM it showed no functional benefit and increased the risk of LVEF declining <50%.
Meta-Analysis (n=1,083)
Does mavacamten improve clinical, functional, and echocardiographic outcomes in adults with obstructive versus non-obstructive hypertrophic cardiomyopathy?
Mavacamten provides significant symptomatic and hemodynamic benefits in obstructive HCM, but lacks functional benefit and poses a high risk of systolic dysfunction in non-obstructive HCM.
Odds Ratio: 4.94 (95% CI 3.25–7.49)
Background Mavacamten, a selective cardiac myosin inhibitor, is a therapeutic option for hypertrophic cardiomyopathy (HCM). Its impact on exercise capacity, health-related quality of life and left ventricular outflow tract (LVOT) obstruction, alongside differential phenotype effects, remains incompletely characterised. This meta-analysis evaluates mavacamten’s efficacy and safety in adults with HCM. Methods We searched PubMed, Scopus and Web of Science through October 2025 for randomised controlled trials (RCTs) assessing mavacamten in HCM. Outcomes included New York Heart Association (NYHA) class, Kansas City Cardiomyopathy Questionnaire (KCCQ-CSS), peak VO₂, LVOT gradient, cardiac structure, biomarkers and adverse events. Data were pooled using random-effects models, stratified by phenotype (obstructive HCM (oHCM) vs non-obstructive HCM (nHCM)). Risk of bias was assessed via Cochrane risk-of-bias tool for randomised trials (RoB-2), alongside trial sequential analysis and Grading of Recommendations, Assessment, Development and Evaluation (GRADE). Results Five RCTs (1083 patients; 444 oHCM, 639 nHCM) were included. In oHCM, mavacamten markedly improved NYHA class (OR 4.94; 95% CI 3.25 to 7.49) and KCCQ-CSS (MD 8.99), with substantial LVOT gradient reductions. Serious adverse events did not increase overall in either phenotype. The risk of left ventricular ejection fraction declining <50% was considerably elevated in nHCM (OR 14.35; 95% CI 5.92 to 34.77)—though based on limited events, requiring cautious interpretation—but not elevated in oHCM (OR 2.08; 95% CI 0.79 to 5.48). Additionally, nHCM patients showed no functional benefit and a suggestive KCCQ-CSS worsening (MD −0.70, 95% CI −1.26 to −0.14). Biomarkers (NT-proBNP, hs-cTnI) decreased substantially across both phenotypes, confirming biological activity. Conclusion Mavacamten appears effective in oHCM, improving symptoms and obstruction with a reassuring safety profile. In nHCM, it drives biochemical and structural remodelling without conferring meaningful symptomatic benefit, while potentially posing a considerably elevated risk of clinically relevant systolic dysfunction. These findings support phenotype-guided precision therapy, urging stringent echocardiographic surveillance and caution regarding off-label use in non-obstructive disease. PROSPERO registration number CRD420251176149.
Alazzam et al. (Mon,) conducted a meta-analysis in Hypertrophic cardiomyopathy (HCM) (n=1,083). Mavacamten was evaluated on NYHA class improvement in obstructive HCM (OR 4.94, 95% CI 3.25 to 7.49). Mavacamten improved NYHA class in obstructive HCM (OR 4.94; 95% CI 3.25-7.49), but in non-obstructive HCM it showed no functional benefit and increased the risk of LVEF declining <50%.