Efficacy of Mavacamten on functional capacity in hypertrophic cardiomyopathy: a meta-analysis, meta-regression, and trial sequential analysis of randomized controlled trials.

内容摘要

Hypertrophic cardiomyopathy (HCM) is characterized by left ventricular hypertrophy, often leading to left ventricular outflow tract (LVOT) obstruction, heart failure, and sudden cardiac death. Mavacamten, a novel cardiac myosin inhibitor, targets the underlying mechanisms of HCM. We searched PubMed, Cochrane Library, and ClinicalTrials.gov up to 1 August 2025 and included six randomized controlled trials comparing Mavacamten to placebo in adults with HCM. The primary outcome was the change in LVOT gradients (post-exercise, post-Valsalva, and resting). Secondary outcomes included N-terminal pro-brain natriuretic peptide (NT-proBNP) levels, left ventricular ejection fraction, peak oxygen consumption (pVO2), and serious adverse events (SAEs). Data were analyzed using a random-effects model, with results reported as mean differences (MD) or risk ratios (RR) with 95% confidence intervals (CI). Meta-regression explored study-level moderators, and retrospective trial sequential analysis assessed the robustness of the findings. Among 632 patients, Mavacamten significantly reduced LVOT gradients: post-exercise (MD:&#xa0;-38.28&#xa0;mmHg, 95% CI:&#xa0;-45.92 to -30.63, P < 0.00001), post-Valsalva (MD:&#xa0;-59.02&#xa0;mmHg, 95% CI:&#xa0;-82.75 to -35.29, P < 0.00001), and resting (MD:&#xa0;-44.50&#xa0;mmHg, 95% CI:&#xa0;-66.49 to -22.51, P < 0.0001). NT-proBNP levels decreased significantly (MD:&#xa0;-617.26 ng/L, 95% CI:&#xa0;-772.43 to -462.09, P < 0.00001), but pVO2 showed no significant change (MD: 0.69 mL/kg/min, 95% CI:&#xa0;-1.12 to 2.50, P =&#xa0;0.45). SAEs were comparable (RR: 1.17, 95% CI: 0.58-2.36, P =&#xa0;0.66). Across primary outcomes, retrospective trial sequential analysis confirms that Mavacamten's reductions in LVOT gradients are conclusive, indicating robust evidence. Mavacamten effectively reduces LVOT gradients and NT-proBNP levels in HCM, but its impact on exercise capacity remains uncertain, with no increased risk of SAEs.