Efficacy and safety of mavacamten in non-obstructive hypertrophic cardiomyopathy: A systematic review and meta-analysis of randomized trials.

BACKGROUND

Non-obstructive hypertrophic cardiomyopathy (nHCM) remains a therapeutic challenge, with limited pharmacological options beyond symptomatic management. Mavacamten, a selective allosteric cardiac myosin inhibitor, has shown benefit in obstructive HCM, but its role in nHCM is uncertain.

METHODS

A systematic search of PubMed, Embase, CENTRAL, and ClinicalTrials.gov was conducted up to November 2025 for placebo-controlled randomized controlled trials (RCTs) enrolling patients with nHCM. Outcomes included Kansas City Cardiomyopathy Questionnaire (KCCQ) score, peak oxygen consumption (pVO2), New York Heart Association (NYHA) functional class, and treatment-emergent adverse events (TEAEs). Pooled mean differences (MDs) and risk ratios (RRs) were estimated using random- or fixed-effects models based on heterogeneity.

RESULTS

Two RCTs (n = 639) met inclusion criteria. Mavacamten showed a nonsignificant improvement in KCCQ (MD: 2.12; 95% CI: -0.98 to 5.22; I2 = 0%) and peak oxygen consumption (MD: 0.36 mL/kg/min; 95% CI: -0.20 to 0.92; I2 = 0%). No significant difference was observed in NYHA class improvement (RR: 1.15; 95% CI: 0.93 to 1.43; I2 = 0%). TEAE incidence was similar between groups (RR: 1.11; 95% CI: 0.34 to 3.58; I2 = 40.8%). Atrial fibrillation occurred more frequently with mavacamten (RR: 1.41; 95% CI: 1.28 to 1.56), whereas palpitations and dizziness did not differ significantly.

CONCLUSIONS

Mavacamten does not significantly enhance symptoms, functional capacity, or health status in nHCM, though safety is comparable to placebo. Ongoing monitoring for arrhythmias and reduced ejection fraction is essential. Larger, longer-term studies are needed to clarify its role in this population.