The Efficacy and Safety of Cardiac Myosin Inhibitors Versus Placebo in Patients With Symptomatic Obstructive Hypertrophic Cardiomyopathy: A Meta-Analysis of Randomized Controlled Trials.

INTRODUCTION

Obstructive hypertrophic cardiomyopathy (oHCM) is a genetic disorder characterized by myocardial hypertrophy, which can obstruct left ventricular outflow. Cardiac myosin inhibitors (CMIs) have emerged as a novel therapeutic agent targeting cardiac muscle hypercontractility.

OBJECTIVE

To compare the efficacy and safety of CMIs mavacamten and aficamten vs. placebo in patients with oHCM.

METHODS

We systematically searched PubMed, Scopus, and Cochrane Central databases for randomized controlled trials (RCTs) comparing mavacamten or aficamten to placebo in patients with symptomatic oHCM. Efficacy outcomes included improvement in peak oxygen consumption (pVO2), New York Heart Association functional class (NYHA-FC) improvement of ≥1 class, change in Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CSS), peak left ventricular outflow tract gradient at rest (rLVOT) and with Valsalva maneuver (vLVOT). Safety outcomes included treatment-emergent adverse events (TEAE), serious adverse events (SAE), and atrial fibrillation (AF). Random effects models generated risk ratios (RRs) and mean differences (MDs) with 95% confidence intervals (CIs). Heterogeneity was assessed using I2 statistics.

RESULTS

The systematic search identified 5 RCTs including 767 patients (mavacamten 30.4%, aficamten 22.2%, placebo 47.4%) with a median follow-up of 24 weeks. Compared to placebo, CMIs were associated with improvement of ≥1 NYHA-FC (RR 2.33; 95% CI, 1.92-2.82), rLVOT (MD -38.70; 95% CI, [-46.30]-[-31.10]), vLVOT (MD -47.29; 95% CI, [-57.99]-[-36.58]), pVO2 (MD 1.66; 95% CI, 1.14-2.18), and KCCQ-CSS (MD 7.76; 95% CI, 5.63-9.90). Safety outcomes were similar between CMIs and placebo.

CONCLUSION

CMIs are an effective and safe short-term treatment for symptomatic oHCM. Long-term outcomes require further investigation.