Efficacy and Safety of Mavacamten and Aficamten in Obstructive and Nonobstructive Hypertrophic Cardiomyopathy: A Systematic Review and Meta-Analysis.

Cardiac myosin inhibitors (CMIs) are novel, disease-modifying therapies for hypertrophic cardiomyopathy (HCM). This meta-analysis evaluates the efficacy of CMIs versus placebo in patients with HCM. A systematic review and meta-analysis of randomized controlled trials involving adults with obstructive and nonobstructive HCM was performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines and registered on PROSPERO. Databases including PubMed, Embase, the Cochrane Library, and ClinicalTrials.gov were searched through September 2025. Random-effects models were performed using standardized mean differences for biomarker and WMDs for echocardiographic parameters. Risk ratios (RRs) were calculated for dichotomous outcomes, with 95% confidence intervals. Seven randomized controlled trials, comprising 1406 patients (732 CMI; 674 placebo), were included. CMIs significantly improved resting [WMD: -57.27 mm Hg (-63.05, -51.49); P < 0.001] and post-Valsalva left ventricular outflow tract gradient [WMD: -55.87 mm Hg (-63.05, -51.49); P < 0.001]. Left ventricular ejection fraction decreased modestly [WMD: -4.74% (-7.22, -2.26); P = 0.0002]. CMIs increased the likelihood of ≥1 New York Heart Association class improvement [RR: 1.94 (1.37, 2.74); P < 0.001] and Kansas City Cardiomyopathy Questionnaire-Clinical Summary Score [WMD: +6.60 points (3.84, 9.35); P < 0.001]. N-terminal pro B-type natriuretic peptide [WMD: -13.35 (-18.04, -8.67); P < 0.001] and cardiac troponin I [WMD: -11.90 (-15.07, -8.73); P < 0.001] declined. Peak oxygen uptake showed no overall change [WMD: +0.64 mL/kg/min (-0.18, 1.47); P = 0.12]. CMIs increased adverse events [RR: 1.07 (1.02, 1.13); P = 0.008], particularly hypertension [RR: 2.19 (1.06, 4.53); P = 0.03]. CMIs improve hemodynamics, functional status, and biomarkers in HCM with an acceptable safety profile and hold promise as disease-modifying therapy, though long-term outcomes require confirmation.

Duke Scholars

Author Stephen Greene Medicine, Cardiology