CMIs are reshaping disease-specific treatment for obstructive hypertrophic cardiomyopathy. A systematic review and meta-analysis published in Progress in Cardiovascular Diseases analyzed four Phase 3 randomized placebo-controlled trials including 726 patients with oHCM, assessing the efficacy and safety of mavacamten and aficamten over 16–30 weeks.

CMIs produced significantly superior outcomes versus placebo. An additional 36% of patients achieved at least one New York Heart Association (NYHA) class improvement, alongside an 8.4-point rise in Kansas City Cardiomyopathy Questionnaire–Clinical Summary Score. Exercise performance improved with an increase in peak oxygen consumption by 1.6 mL/kg/min and reduced ventilatory inefficiency (VE/VCO₂: −2.0).

Biomarker analysis revealed marked reductions in NT-proBNP (−79%) and high-sensitivity troponin I (−50%). Echocardiography and cardiovascular magnetic resonance showed a mean LVOT gradient decrease of −40 mmHg and evidence of favorable cardiac remodeling. Although transient left ventricular ejection fraction (LVEF) reductions below 50% occurred, no patient developed heart failure.

These findings demonstrate a consistent class effect of CMIs, establishing mavacamten and aficamten as cornerstone therapies for improving hemodynamic and symptomatic outcomes in oHCM.