Efficacy and safety of cardiac myosin inhibitors in obstructive hypertrophic cardiomyopathy: Systematic review and comprehensive frequentist and Bayesian meta-analyses of Phase 3 randomized controlled trials

AIMS: Data on cardiac myosin inhibitors (CMIs) in obstructive hypertrophic cardiomyopathy (oHCM) are rapidly emerging. This systematic review and meta-analysis evaluated the efficacy and safety of CMIs in randomized placebo-controlled trials. METHODS: Phase 3 randomized placebo-controlled trials published up to 22-Apr-2025 were included. Outcomes extracted included symptoms, cardiopulmonary exercise testing (CPET), biomarkers, transthoracic echocardiography (TTE), cardiovascular magnetic resonance (CMR), and safety data. Frequentist (common/fixed effect, random) and Bayesian meta-analyses were performed using trial-level data to pool estimates of effects. RESULTS: -2.0 (-2.7, -1.3). CMIs significantly reduced NT-proBNP -79 % (-81 %, -77 %) and hs-cTnI -50 % (-54 %, -46 %). CMIs led to significant reductions in resting LVOT-G -40 (-45, -35) mmHg and favourable cardiac remodelling in other TTE and CMR parameters. Although CMIs increased the likelihood of LVEF <50 %, consistent with its known mechanism of action, none of these patients developed heart failure. No significant differences were seen in safety outcomes. CONCLUSIONS: Mavacamten and aficamten significantly improve symptoms, enhance exercise performance, improve cardiac biomarkers, reduce LVOT obstruction, and promote favourable cardiac remodelling. These findings suggest a class effect of CMIs. PROSPERO REGISTRATION: CRD42024582096.