Mavacamten improves functional status in obstructive hypertrophic cardiomyopathy without increasing serious adverse events: a systematic review and meta-analysis
A Taveras Franco, L Cruz, I Figueroa, O RuizAbstract
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.