Key result
Mavacamten yields ~5.5-fold higher odds of NYHA class improvement in oHCM vs control.
Why the study?
Traditional therapies for obstructive hypertrophic cardiomyopathy are symptomatic and septal reduction is invasive. Although mavacamten directly targets hypercontractility, its overall impact on functional capacity and safety across studies had not been systematically assessed.
Does mavacamten improve ≥1 NYHA functional class without increasing treatment-emergent serious adverse events in adults with obstructive hypertrophic cardiomyopathy?
Meta-Analysis (n=1,379)
Does mavacamten improve ≥1 NYHA functional class without increasing treatment-emergent serious adverse events in adults with obstructive hypertrophic cardiomyopathy?
This meta-analysis demonstrates that mavacamten significantly improves NYHA functional status in patients with obstructive hypertrophic cardiomyopathy without increasing serious adverse events across clinical trial and real-world settings.
Supports mavacamten use to improve functional class in oHCM without increasing serious adverse events; confirms and extends randomized trial evidence.
Background Obstructive hypertrophic cardiomyopathy (oHCM) is the most common inherited heart disease and a major cause of heart failure symptoms and sudden cardiac death. Functional limitation, often reflected by NYHA class, remains central to prognosis. Traditional therapies are symptomatic, and septal reduction is invasive. Mavacamten, the first selective cardiac myosin inhibitor, directly targets hypercontractility, but its overall impact on function and safety across studies has not been systematically assessed. Purpose To evaluate the effect of mavacamten on functional capacity and safety in patients with oHCM. Methods A systematic review and meta-analysis of clinical trials and observational studies evaluating mavacamten in adults with oHCM was performed. The primary outcome was ≥1 NYHA class improvement. Safety was assessed by treatment-emergent serious adverse events (TESAEs). Pooled odds ratios (OR) with 95% confidence intervals (CI) were calculated using a random-effects model. Results Nine studies were included: six clinical trials (n=939) and three observational studies (n=440). Among four randomized controlled trials (EXPLORER-HCM, EXPLORER-CN, VALOR-HCM, MAVERICK-HCM; n=503), mavacamten significantly increased the likelihood of ≥1 NYHA class improvement compared with control (177/273 vs 63/230; OR 5.55; 95% CI 1.94–15.87; p=0.001). Rates of TESAEs were similar between groups (37/218 vs 30/203; OR 1.16; 95% CI 0.67–2.01; p=0.59). Open-label extension studies (PIONEER-OLE, HORIZON-HCM; n=436) demonstrated sustained functional improvement. Observational studies further supported these findings in real-world populations, although they were not included in the quantitative synthesis. Conclusion Mavacamten significantly improves functional status in patients with oHCM without increasing serious adverse events. These findings support its role as a disease-targeted therapy with meaningful clinical benefit, with consistent effectiveness observed across both clinical trial and real-world settings.
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Franco et al. (2026) conducted a meta-analysis in Obstructive hypertrophic cardiomyopathy (oHCM) (n=1,379). Mavacamten vs. Control was evaluated on ≥1 NYHA class improvement (OR 5.55, 95% CI 1.94-15.87, p=0.001). Mavacamten significantly increased ≥1 NYHA class improvement vs control in oHCM (OR 5.55; 95% CI 1.94–15.87; p=0.001) without increasing serious adverse events.
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