Aficamten or Metoprolol Monotherapy for Obstructive Hypertrophic Cardiomyopathy
Pablo Garcia-Pavia1,2, Martin S Maron3, Ahmad Masri4
1Hospital Universitario Puerta de Hierro de Majadahonda, Instituto Investigación Sanitaria Puerta de Hierro-Segovia de Arana, Centro de Investigación Biomédica en Red Enfermedades Cardiovaculares (CIBERCV), Madrid.
The New England Journal of Medicine
|September 1, 2025
Summary
Aficamten monotherapy significantly improved exercise capacity and reduced symptoms in obstructive hypertrophic cardiomyopathy (HCM) patients compared to metoprolol. This cardiac myosin inhibitor offers a superior treatment option for HCM.
Area of Science:
- Cardiology
- Pharmacology
- Clinical Trials
Background:
- Obstructive hypertrophic cardiomyopathy (HCM) is often treated with beta-blockers, but evidence for their efficacy is limited.
- Aficamten, a cardiac myosin inhibitor, has shown promise in improving HCM symptoms and exercise capacity when used with standard medications.
Purpose of the Study:
- To compare the efficacy of aficamten monotherapy versus metoprolol monotherapy in patients with symptomatic obstructive HCM.
- To evaluate the impact of aficamten on exercise capacity, functional status, and hemodynamic parameters.
Main Methods:
- An international, double-blind, double-dummy trial randomized 175 adults with symptomatic obstructive HCM to receive either aficamten or metoprolol.
- The primary endpoint was the change in peak oxygen uptake at 24 weeks. Secondary endpoints included improvements in NYHA functional class, KCCQ-CSS, and hemodynamic measures.
Main Results:
- Aficamten monotherapy significantly increased peak oxygen uptake compared to metoprolol (2.3 ml/kg/min difference, P<0.001).
- Patients receiving aficamten showed greater improvements in NYHA class, KCCQ-CSS, left ventricular outflow tract gradient, NT-proBNP, and left atrial volume index.
- Adverse events were similar between the aficamten and metoprolol groups.
Conclusions:
- Aficamten monotherapy is superior to metoprolol monotherapy for improving exercise capacity and hemodynamics in symptomatic obstructive HCM.
- Aficamten demonstrates significant clinical benefits in reducing symptoms and improving quality of life for HCM patients.
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