- Question
- Is monotherapy with aficamten, a cardiac myosin inhibitor, superior to monotherapy with metoprolol, the usual beta-blocker, in patients with symptomatic obstructive hypertrophic cardiomyopathy?
- Design
- International, randomized 1:1, double-blind, double-dummy trial enrolling 175 patients (88 on aficamten and 87 on metoprolol), with the main assessment at 24 weeks.
- Population
- Adults with symptomatic obstructive hypertrophic cardiomyopathy; mean age 58 years, 58.3% men, with a mean left ventricular outflow tract gradient of 47 mm Hg at rest and 74 mm Hg after Valsalva.
- Intervention
- Aficamten at a daily dose of 5 to 20 mg plus metoprolol placebo, as monotherapy.
- Control
- Metoprolol succinate at a daily dose of 50 to 200 mg plus aficamten placebo, as monotherapy.
- Primary outcome
- Change in peak oxygen uptake (pVO2) measured by cardiopulmonary exercise testing from baseline to week 24.
- Results
- Peak oxygen uptake changed by +1.1 ml/kg/min with aficamten and −1.2 ml/kg/min with metoprolol (least-squares mean between-group difference 2.3 ml/kg/min; 95% CI 1.5 to 3.1; P<0.001). Aficamten also significantly improved NYHA class, KCCQ-CSS, outflow tract gradient, NT-proBNP and left atrial volume index; there was no significant difference in left ventricular mass index.
- Safety
- Adverse events appeared similar in the two treatment groups.
- Conclusion
- In symptomatic obstructive hypertrophic cardiomyopathy, aficamten monotherapy was superior to metoprolol monotherapy in improving exercise capacity and hemodynamics and reducing symptoms.
- Why it matters
- It challenges the role of beta-blockers as first-line initial therapy and supports cardiac myosin inhibitors as an initial option in this population.
Card generated automatically with AI from the abstract of the original publication and the trial registry; every figure was checked against those sources. It may contain errors: verify the data at the source before using it for clinical decisions.
Generated on October 14, 2026