Key result
Cardiac myosin inhibitors cut resting LVOT gradients by ~70 mm Hg vs placebo in symptomatic HCM.
Why the study?
Do cardiac myosin inhibitors (mavacamten and aficamten) improve symptomatic status, LVOT gradients, and cardiac biomarkers compared to placebo in adult patients with symptomatic hypertrophic cardiomyopathy?
Meta-Analysis (n=1,081)
Do cardiac myosin inhibitors (mavacamten and aficamten) improve symptomatic status, LVOT gradients, and cardiac biomarkers compared to placebo in adult patients with symptomatic hypertrophic cardiomyopathy?
This meta-analysis of 6 RCTs confirms that cardiac myosin inhibitors (mavacamten and aficamten) significantly reduce LVOT gradients, improve NYHA functional class and quality of life (KCCQ-CSS), and lower cardiac biomarkers in symptomatic HCM without increasing serious adverse events or atrial fibrillation.
Answers are grounded in this paper and cite their sources.
Supports myosin inhibitor use for obstruction relief in symptomatic HCM; confirms pooled efficacy across randomized trials.
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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Hazique et al. (2025) conducted a meta-analysis in Symptomatic hypertrophic cardiomyopathy (n=1,081). Cardiac myosin inhibitors vs. Placebo was evaluated on Left ventricular outflow tract (LVOT) gradient at rest (MD -70.22 mm Hg, 95% CI -85.42 to -55.03, p=<0.01). Cardiac myosin inhibitors reduced resting left ventricular outflow tract gradients compared to placebo in patients with symptomatic hypertrophic cardiomyopathy.
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