Aficamten Outperforms Metoprolol in increasing exercise performance in symptomatic Obstructive HCM: JAMA
A prespecified analysis of the MAPLE-HCM trial showed that aficamten monotherapy provided greater improvements in a wide range of exercise performance measures compared with metoprolol in patients with symptomatic obstructive hypertrophic cardiomyopathy (oHCM). Aficamten enhanced patients' ability to adapt to multiple phases of exercise, demonstrating superior functional benefits. These findings suggest that aficamten may be a promising first-line treatment option for symptomatic oHCM, offering better exercise capacity and symptom control than traditional beta-blocker therapy.
Patients with obstructive hypertrophic cardiomyopathy (oHCM) endure life-altering exercise limitations. Current treatment guidelines recommend β-blockers as first-line therapy primarily based on expert opinion. The Metoprolol vs Aficamten in Patients with Left Ventricular Outflow Tract Obstruction on Exercise Capacity in HCM (MAPLE-HCM) trial characterizes comprehensive exercise response to aficamten monotherapy vs β-blockade (metoprolol).
A study was done to determine the effect of aficamten compared with metoprolol across all stages of exercise using 16 quantitative measures in individuals with oHCM. This was a prespecified secondary analysis of the MAPLE-HCM study, a phase 3, randomized, active-control trial conducted from June 2023 to March 2025 with data analyzed between May and July 2025 at 71 sites in North America, South America, Europe, Israel, and China. Patients with symptomatic oHCM with objective evidence of exercise intolerance (peak oxygen uptake [pVO2] <100% of predicted) were included.
Those with a history of atrial fibrillation (paroxysmal or persistent), medical indication for β-blockers or calcium channel blockers prohibiting drug discontinuation, or intolerance or medical contraindication to β-blockers were excluded. The main outcomes were submaximal exercise minute ventilation (VE)/carbon dioxide output (VCO2) slope and anaerobic threshold; peak exercise duration, workload, heart rate and heart rate reserve; and postexercise oxygen recovery rates; and composite variables, such as circulatory power.
This prespecified analysis of MAPLE-HCM demonstrated monotherapy with aficamten was superior to metoprolol in promoting adaptation to multiple phases of exercise in patients with symptomatic oHCM and supports aficamten as first-line therapy for oHCM.
Reference:
Lewis GD, Garcia-Pavia P, Masri A, et al. Exercise Performance With Aficamten vs Metoprolol in Obstructive Hypertrophic Cardiomyopathy: The MAPLE-HCM Randomized Clinical Trial. JAMA Cardiol. Published online June 17, 2026. doi:10.1001/jamacardio.2026.1730
