Efficacy and Safety of Cardiac Myosin Inhibitors in Hypertrophic Cardiomyopathy: A Meta-Analysis of Randomized Controlled Trials

Hypertrophic cardiomyopathy (HCM) is a genetic cardiac disorder characterized by structural and functional abnormalities. Current management strategies, such as medications and septal reduction therapies, have significant limitations and risks. Recently, cardiac myosin inhibitors (CMIs) like mavacamten and aficamten have shown promise as noninvasive treatment options. This meta-analysis aims to evaluate the efficacy and safety of CMIs in HCM patients. PubMed/MEDLINE, Embase, the Cochrane Library, Ovid, and ClinicalTrials.gov were searched for randomized controlled trials (RCTs) that compared CMIs to control treatments in HCM patients from inception till June 15, 2024. A random-effects model was used to pool odds ratios (ORs) for dichotomous outcomes and mean differences (MDs) for continuous outcomes along with the corresponding 95% confidence intervals (CIs). Heterogeneity was assessed using the χ 2 test and Higgins I 2 statistic, and sensitivity and subgroup analyses were performed. Six RCTs involving 826 patients were included. CMI therapy significantly reduced resting left ventricular outflow tract (LVOT) gradient (MD, −37.64; 95% CI, −46.71 to −28.56), Valsalva LVOT gradient (MD, −46.04; 95% CI, −57.60 to −34.48), post-exercise LVOT peak gradient (MD, −48.64; 95% CI, −68.20 to −28.88), N-terminal pro-b-type natriuretic peptide levels (MD, −1.05; 95% CI, −1.64 to −0.47), and cardiac troponin I levels (MD, −7.96; 95% CI, −12.84 to −3.07). Improvements were observed in peak oxygen consumption (MD, 1.20; 95% CI, 0.23–2.17) and patient-reported outcomes (Kansas City Cardiomyopathy Questionnaire Clinical Summary Score: MD, 6.44; 95% CI, 3.50–9.37), with more patients achieving New York Heart Association class improvement >1 (OR, 4.05; 95% CI, 2.61–6.30). Treatment-emergent adverse events were higher with CMI therapy (OR, 1.45; 95% CI, 1.02–2.05), but serious adverse events and other safety outcomes were comparable in both groups. CMIs, including mavacamten and aficamten, significantly improve clinical outcomes in HCM patients with a manageable safety profile. These results indicate that CMIs offer a promising noninvasive alternative to septal reduction therapies.