MAPLE-HCM: Aficamten Proves Superiority to Metoprolol in Hypertrophic Cardiomyopathy

Aficamten, a cardiac myosin inhibitor from Cytokinetics which reduces left ventricular outflow tract gradients, decreases hypertrophic cardiomyopathy (HCM) symptoms, and improves exercise capacity when added to standard of care medications, has proven noninferiority versus beta-blockers in the recent MAPLE-HCM trial.¹

Presented at the European Society of Cardiology Congress 2025 in Madrid, on August 30, 2025, the trial’s primary endpoint was change in peak oxygen uptake at week 24, and secondary endpoints included improvement at week 24 in the New York Heart Association (NYHA) functional class and Kansas City Cardiomyopathy Questionnaire clinical summary score (KCCO-CSS).¹

“I think this trial is going to profoundly change the way we approach pharmacological therapy in HCM,” lead investigator Pablo Garcia-Pavia, MD, PhD, head of the heart failure and inherited cardiac diseases unit at the Hospital Universitario Puerta de Hierro, said in an interview with HCPLive. “Currently, we have been using beta-blockers, and the results of this trial show that aficamten is superior to meoprolol, the most commonly used beta-blocker for this indication. So with this, I think we have a strong ground in order to change the algorithm of therapies that we use for this disease.”

The international, double-blind, double-dummy trial included 175 adult participants with symptomatic obstructive HCM, with a mean age of 58 years and a mean left ventricular outflow tract gradient of 47 mm Hg at rest and 74 mm Hg after the Valsalva maneuver. After a 1:1 ratio random assignment, 88 patients were included in the aficamten group and 87 in the metoprolol group.¹

At 24 weeks, peak oxygen uptake had changed by 1.1 ml per kilogram of body weight per minute (95% CI, 0.5 to 1.7) in the aficamtent group and -1.2 ml per kilogram per minute (95% CI, -1.7 to -0.8) in the metoprolol group (least-squares mean between-group difference, 2.3 ml per kilogram per minute; 95% CI, 1.5 to 3.1; P <.001). Patients receiving aficamten also had significantly greater improvements in NYHA class, KCCQ-CSS, left ventricular outflow tract gradient, NT-proBNP level, and left atrial volume index than patients given metoprolol.¹

However, despite these results, Garcia-Pavia and colleagues also noted several limitations, which they described as precluding assessment of the relative effect of aficamten and metoprolol on longer-term outcomes. First, the team noted the possibility for bias regarding investigator assumption of treatment assignment, given the negative chronotropic effect of metoprolol. Additionally, other nonvasodilating beta-blockers may have effects different from those of metoprolol, and the dose-adjustment protocol used for metoprolol may differ from strategies implemented in local practice.¹

“The MAPLE-HCM trial confirmed the therapeutic safety and efficacy of aficamten in obstructive HCM, similar to the previous SEQUOIA-HCM trial,” Amrut Ambardekar, MD, wrote in a related editorial for NEJM. “Although head-to-head comparisons are lacking, the current data shows that myosin inhibition with either mavacamten or aficamten could be a suitable option for symptomatic obstructive HCM.”²

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