Aficamten Outperforms Metoprolol in Obstructive Hypertrophic Cardiomyopathy, With Pablo Garcia-Pavia, MD, PhD

Aficamten demonstrated superior clinical and functional benefits compared with metoprolol in patients with symptomatic obstructive hypertrophic cardiomyopathy (HCM), according to results from the MAPLE-HCM trial presented at the European Society of Cardiology (ESC) Congress 2025.

The international, double-blind study randomized 175 adults with obstructive HCM to receive aficamten (5–20 mg daily) or metoprolol (50–200 mg daily). The primary endpoint was change in peak oxygen uptake (pVO₂) at 24 weeks, with secondary endpoints including New York Heart Association (NYHA) functional class, Kansas City Cardiomyopathy Questionnaire clinical summary score (KCCQ-CSS), and hemodynamic measures.

At 24 weeks, pVO₂ increased by 1.1 mL/kg/min in the aficamten group but decreased by 1.2 mL/kg/min in the metoprolol group, yielding a significant between-group difference of 2.3 mL/kg/min (95% CI, 1.5–3.1; P <.001). Aficamten recipients also experienced greater improvements in NYHA class, KCCQ-CSS, left ventricular outflow tract gradients, NT-proBNP levels, and left atrial volume index.

“I think this trial is going to profoundly change the way we approach pharmacological therapy in HCM,” said lead investigator Pablo Garcia-Pavia, MD, PhD. “Currently, we have been using beta-blockers, and the results show that aficamten is superior to metoprolol, the most commonly used beta-blocker for this indication.”

Despite these promising results, investigators noted several limitations, including potential bias due to the recognizable chronotropic effects of metoprolol and uncertainty about how other nonvasodilating beta-blockers might compare. Additionally, the trial design did not address long-term outcomes.

Commenting in the New England Journal of Medicine, Amrut Ambardekar, MD, emphasized that MAPLE-HCM confirms the efficacy and safety of aficamten, echoing findings from the earlier SEQUOIA-HCM trial. “Although head-to-head comparisons are lacking, the current data show that myosin inhibition with either mavacamten or aficamten could be a suitable option for symptomatic obstructive HCM,” he wrote.

References

1. Garcia-Pavia P, Maron M, Masri A, et al. Aficamten or Metoprolol Monotherapy for Obstructive Hypertrophic Cardiomyopathy. NEJM. August 30, 2025. Accessed August 30, 2025. DOI: 10.1056/NEJMoa2504654

2. Ambardekar A. Expanding the Role of Myosin Inhibition in Hypertrophic Cardiomyopathy – A Tale of Two Conditions. NEJM. August 30, 2025. Accessed August 30, 2025. DOI: 10.1056/NEJMe2512100