Aficamten vs Metoprolol for Obstructive Hypertrophic Cardiomyopathy

Beta-blockers and nondihydropyridine calcium-channel blockers have been standard-of-care (SOC) medications for patients with symptomatic obstructive hypertrophic cardiomyopathy (oHCM), even though these agents do not directly affect the underlying pathophysiology of the disease. Cardiac myosin inhibitors act by decreasing the number of myosin heads binding to actin, reducing the pathologic hypercontractility of HCM, and have been shown to improve exercise capacity and alleviate symptoms in oHCM when added to SOC medications. Cardiac myosin inhibitors are currently considered as second-line therapy in the absence of head-to-head comparison studies vs SOC medications. The aim of the ongoing phase 3 study MAPLE-HCM (Metoprolol vs Aficamten in Patients With LVOT Obstruction on Exercise Capacity in HCM) is to fill this evidence gap by evaluating aficamten as both first-line therapy for newly diagnosed oHCM and as a monotherapy alternative for patients currently on SOC drugs. The authors describe the rationale, design, and baseline characteristics of patients in this study. (Phase 3 Trial to Evaluate the Efficacy and Safety of Aficamten Compared to Metoprolol Succinate in Adults With Symptomatic oHCM [MAPLE-HCM]; NCT05767346).