SynthesisAmerican journal of cardiovascular drugs : drugs, devices, and other interventions2025
Cardiac Myosin Inhibitors for Obstructive Hypertrophic Cardiomyopathy: A Meta-analysis of Randomized Placebo-Controlled Trials.
Synthesis in American journal of cardiovascular drugs : drugs, devices, and other interventions, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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11 authors.
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Abstract
backgroundCardiac myosin inhibitors (CMI) have emerged as the first disease-specific, noninvasive therapy with promising results in patients with hypertrophic cardiomyopathy. However, its role in obstructive hypertrophic cardiomyopathy (oHCM) remains uncertain, especially in secondary endpoints of randomized controlled trials (RCTs).
methodsWe systematically searched PubMed, Embase, Web of Science, and Clinicaltrials.gov from inception to June 2024 for RCTs comparing CMI versus placebo in patients with oHCM. We applied a random-effects model to evaluate efficacy and safety outcomes and primary or secondary outcomes of RCTs.
resultsWe included five RCTs comprising 767 patients, of whom 402 (52.5%) were randomized to CMI. Relative to placebo, CMI were associated with a higher rate of improvement of at least one New York Heart Association (NYHA) functional class [risk ratio (RR) 2.33; 95% confidence interval (CI) 1.92-2.82]. In addition, CMI reduced resting left ventricular outflow tract (LVOT) [mean difference (MD) - 42.51 mmHg; 95% CI - 59.27 to - 25.75] and the provoked LVOT gradients (MD - 46.12 mmHg; 95% CI - 55.70 to - 36.54). However, CMI significantly increased the risk of reaching a left ventricular ejection fraction below 50% (RR 4.80; 95% CI 1.42-16.20), affecting 8% of patients during long-term follow-up of up to 120 weeks. There was no significant interaction across subgroups of class representatives, pointing to a class effect. The benefit-risk analysis indicated a larger benefit for NYHA class improvement than risk for systolic dysfunction.
conclusionIn patients with oHCM, mavacamten and aficamten as a class improve clinical and hemodynamic endpoints compared with placebo, albeit with a higher incidence of a reduction in left ventricular ejection fraction. REGISTRATION: PROSPERO CRD42023468079.
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