LATE-breaking results from ESC 2025 show that aficamten, a cardiac myosin inhibitor, significantly improves exercise capacity and symptoms compared with metoprolol in patients with symptomatic obstructive hypertrophic cardiomyopathy (HCM), including treatment-naïve individuals.
Beta-blockers are commonly used to manage obstructive HCM, but they do not address the underlying hypercontractility and evidence for their efficacy is limited. The MAPLE-HCM trial was a Phase III, randomised, double-blind, double-dummy study conducted across 71 sites worldwide, comparing aficamten and metoprolol as monotherapy in adults with symptomatic obstructive HCM. Eligible patients had NYHA Class II–III symptoms, reduced exercise capacity (age- and sex-predicted peak oxygen uptake <100%), and impaired quality of life (KCCQ-CSS ≤90). Participants were randomised 1:1 to aficamten (5–20 mg titrated) or metoprolol (50–200 mg titrated) over 24 weeks. The primary endpoint was change in peak oxygen uptake assessed by cardiopulmonary exercise testing.
Among 175 participants (mean age: 58 years, 42% women), including 30% treatment-naïve, aficamten significantly increased peak oxygen uptake by 1.1 mL/kg/min, whereas metoprolol saw a decrease of 1.2 mL/kg/min, yielding a least-squares mean difference of 2.3 mL/kg/min (95% CI 1.5–3.1; p<0.001). Symptom improvements were also greater with aficamten: 51.1% of patients achieved ≥1 class improvement in NYHA functional class versus 26.4% with metoprolol, and KCCQ-CSS scores improved by 15.8 points versus 8.7 points. Haemodynamic parameters including left ventricular outflow tract gradient, left atrial volume, and NT-proBNP levels also improved more in the aficamten group. Safety was comparable, with serious adverse events in 8.0% and 6.9% of aficamten and metoprolol patients, respectively.
These findings suggest that aficamten may be considered not only as second-line therapy for persistent symptoms but also as first-line monotherapy, offering substantial improvements in exercise capacity, symptom burden, and haemodynamics compared with traditional beta-blocker treatment.
Reference
Garcia-Pavia P. MAPLE-HCM: aficamten vs metoprolol in oHCM. ESC Congress 2025, 29 August-1 September, 2025.
