Cardiac myosin inhibitors for hypertrophic cardiomyopathy: a systematic review and meta-analysis of randomized controlled trials

Background/objective: HCM is a structural disorder of the myocardium that leads to sudden cardiac death in young adults. We synthesized an updated understanding of the role of Cardiac Myosin Inhibitors (CMIs) in HCM by pooling data from RCTs. Methods: We identified six published RCTs, involving 826 participants. Data were extracted pertaining to study characteristics; primary outcomes of interest-(1) change from baseline in resting left ventricular outflow tract (LVOT) peak gradient, (2) change from baseline in Valsalva LVOT peak gradient, and (3) improvement of ≥1 NYHA class-and secondary outcomes. These were pooled using Review Manager 5.4, employing a random-effects model, and reported as odds ratios (ORs) or mean differences (MDs). Results: We found statistically significant between-group difference favoring CMIs in change from baseline in LVOT peak gradient: at rest (MD -39.33; -53.01 to -25.64), post-Valsalva (MD -48.99; -53.96 to -44.03), and post-exercise (MD -37.11; -44.34 to -29.87); ≥1 NYHA class improvement (OR 4.10; 2.79-6.02), change from baseline in peak oxygen uptake (MD -37.11; -44.34 to -29.87), LVOT gradient ≤30 mm hg (RR 14.89; 7.47-29.67), participants eligible for septal reduction therapy (RR 0.26; 0.18-0.36), and change from baseline in KCCQ-CSS score (MD 8.54; 5.36-11.71). Subgrouping by intervention type (mavacamten vs. aficamten) revealed non-significant results for all primary outcomes. Conclusions: CMIs can contribute to improving key efficacy outcomes for patients with HCM while reducing incidence of SRT.