N Engl J Med

ESC 2025: Cardiac myosin inhibitor outperforms metoprolol in hypertrophic cardiomyopathy

September 4, 2025

Aficamten demonstrated superior efficacy and comparable safety to metoprolol, suggesting cardiac myosin inhibition may be a more effective first-line therapy for obstructive hypertrophic cardiomyopathy (HCM) than traditional beta-blockade. These findings, shared at the annual congress of the European Society of Cardiology, may prompt guideline revisions favoring cardiac myosin inhibitors as initial therapy.

Study details: In the phase 3, double-blind, double-dummy MAPLE-HCM trial (NCT05767346), 175 patients (mean age, 58 years; 58% male) with symptomatic obstructive HCM and preserved ejection fraction (≥60%) were randomized across global centers. Patients received either aficamten (starting at 5 mg daily, titrated up to 20 mg) or metoprolol (starting at 50 mg, titrated up to 200 mg), with matching placebos in each arm. Primary endpoint: change in peak oxygen uptake (VO₂) at 24 weeks.

Results: Mean peak VO₂ rose steadily in the aficamten group (+1.1 mL/kg/min) and declined in the metoprolol group (–1.2 mL/kg/min), yielding a significant between-group difference of 2.3 mL/kg/min (P<.001). Improvements in NYHA class, KCCQ-CSS, LVOT gradient, NT-proBNP, and left atrial volume index also favored aficamten. No significant difference was observed in LV mass index. Adverse event rates were similar between groups.

Source:

Garcia-Pavia P, et al; MAPLE-HCM Investigators. (2025, August 30). N Engl J Med. Aficamten or Metoprolol Monotherapy for Obstructive Hypertrophic Cardiomyopathy. https://pubmed.ncbi.nlm.nih.gov/40888697/