MAPLE-HCM: Aficamten meets efficacy endpoints in obstructive HCM

Aficamten outperformed metoprolol in improving exercise capacity, quality-of-life, symptoms, and structural remodelling in patients with symptomatic obstructive hypertrophic cardiomyopathy (HCM). According to the authors, these data support the use of aficamten as a potential first-line therapy for this patient population.

The phase 3 MAPLE-HCM trial (NCT05767346) randomised 175 patients with symptomatic obstructive HCM 1:1 to the cardiac myosin inhibitor aficamten or the beta-blocker metoprolol. Included patients were either treatment naïve or underwent a 2-week washout period of prior therapy. Exercise capacity (pVO2) was the primary outcome. Dr Pablo Garcia-Pavia (University Hospital Puerta de Hierro Majadahonda, Spain) presented the primary findings [1].

After 24 weeks of therapy, the mean change from baseline in pVO2 was +1.1 ml/kg/min in the aficamten group and -1.2 ml/kg/min in the metoprolol group, representing a clinically meaningful difference of 2.3 ml/kg/min (P<0.0001). In addition, there were significant improvements in the Kansas City Cardiomyopathy Questionnaire (KCCQ) - Clinical Symptom Score (CSS), NT-proBNP levels, post-Valsalva left ventricular outflow tract (LVOT) gradient, and left atrial volume index (LAVI) with aficamten compared with metoprolol.

“Aficamten was generally well tolerated,” said Dr Garcia-Pavia. “One patient discontinued due to adverse events, versus 3 patients in the metoprolol group.” Moreover, only 4 patients on aficamten had at least 1 dose down-titration compared with 26 patients in the metoprolol arm. “We did see a mean change in left ventricular ejection fraction (LVEF) of -5.3% in the aficamten arm, but only 1 patient had an LVEF < 50% as measured by the core lab,” added Dr Garcia-Pavia.

“These findings support the use of aficamten monotherapy as a potential first-line standard-of-care in patients with symptomatic obstructive HCM,” concluded Dr Garcia-Pavia.

1. Garcia-Pavia P, et al. Aficamten vs metoprolol as monotherapy for symptomatic obstructive hypertrophic cardiomyopathy. Hotline 2, ESC Congress 2025, 29 August – 1 September, Madrid, Spain.

Medical writing support was provided by Robert van den Heuvel.

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Posted on 2 September 20257 November 2025