Efficacy and Safety of Mavacamten in Hypertrophic Cardiomyopathy: A Systematic Review and Meta-analysis of Randomized Controlled Trials

Abstract

Background and Purpose: Hypertrophic cardiomyopathy (HCM) is a genetic myocardial disease marked by sarcomeric hypercontractility, diastolic dysfunction, and, frequently, dynamic left-ventricular outflow tract (LVOT) obstruction. Mavacamten, a selective cardiac myosin inhibitor, directly targets excessive contractility and may improve functional capacity and quality of life. This meta-analysis quantitatively evaluated the efficacy and safety of mavacamten across randomized controlled trials in obstructive and non-obstructive HCM.

Methods: Electronic databases were searched for phase II–III randomized trials of mavacamten in adults with HCM. Data were pooled using random-effects meta-analysis (DerSimonian–Laird method). Continuous outcomes were expressed as standardized mean differences (SMDs) and categorical outcomes as odds ratios (ORs), each with 95% confidence intervals (CIs). Heterogeneity was assessed using I² and τ² statistics. Subgroup analyses were performed by disease phenotype.

Results: Five trials (n = 1,022) met inclusion criteria. Mavacamten significantly improved peak VO₂ versus placebo (SMD 0.33; 95% CI 0.09–0.57; P = 0.007), with greater benefit in obstructive HCM (SMD 0.49) than non-obstructive disease (SMD 0.20). Functional improvement (≥1 NYHA class) was more frequent with mavacamten (OR 2.51; 95% CI 1.08–5.86; P = 0.03), driven by the obstructive subgroup (OR 4.59). Quality-of-life scores (KCCQ-CSS) improved modestly overall (SMD 0.33; P = 0.04), and post-exercise LVOT gradient decreased markedly (SMD −1.07; P < 0.00001). Any adverse event was more common with mavacamten (OR 1.84; P = 0.02), but serious events and mortality were comparable to placebo.

Conclusions: Mavacamten provides meaningful improvements in exercise capacity, symptoms, and LVOT hemodynamics, particularly in obstructive HCM, with an acceptable safety profile. These findings support its role as a disease-specific therapy targeting sarcomeric hypercontractility in hypertrophic cardiomyopathy.