Efficacy and safety of myosin inhibitors for symptomatic hypertrophic cardiomyopathy: systematic review and meta-analysis

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Introduction Hypertrophic cardiomyopathy (HCM) is a common genetic cardiac disorder associated with significant morbidity and mortality. Cardiac myosin inhibitors (MIs), including mavacamten and aficamten, offer a novel therapeutic approach for HCM. Material and methods An online database search was performed from inception to September 2024. We selected randomized controlled trials (RCTs) that compared mavacamten with placebo/guideline medical treatment for HCM. Results Six RCTs involving 1,081 participants were analyzed. Cardiac myosin inhibitors significantly reduced left ventricular outflow tract (LVOT) gradients at rest (–70.22 mm Hg, 95% CI: –85.42 to –55.03) and during the Valsalva maneuver (–61.44 mm Hg, 95% CI: –71.10 to –51.78). Patients experienced improved functional status, with a pooled risk ratio (RR) of 2.21 (95% CI: 1.75 to 2.80, p < 0.05) for at least one NYHA class improvement and an enhanced Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CSS) (+7.80 points, 95% CI: 4.58 to 11.02, p < 0.05). Biomarkers, including NT-proBNP (–69.41 pg/ml, 95% CI: –87.06 to –51.75, p < 0.05) and cardiac troponin I (cTnI) (–42.66 ng/l, 95% CI: –48.47 to –36.85, p < 0.05), showed significant reductions. Reductions in left ventricular ejection fraction (LVEF) were observed, with aficamten demonstrating a greater reduction (–10.35%, 95% CI: –13.48 to –7.21) compared to mavacamten (–2.50%, 95% CI: –6.21 to 1.20). Safety analyses showed no significant increase in treatment emergent adverse events (TEAEs) (RR = 1.02, 95% CI: 0.92 to 1.14), serious adverse events (SAEs) (RR = 0.69, 95% CI: 0.37 to 1.28), or atrial fibrillation (RR = 0.77, 95% CI: 0.27 to 2.23). Conclusions MIs significantly improve symptomatic, functional, and biomarker outcomes in symptomatic HCM while maintaining an acceptable safety profile, highlighting their potential as a transformative treatment option. Further studies are warranted to evaluate long-term efficacy and safety.

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