Aficamten versus Metoprolol in Obstructive Hypertrophic Cardiomyopathy: Recent Analyses of the MAPLE-HCM Trial

This article is based on presentations of a late breaking clinical trial at the European Society of Cardiology (ESC) Congress in conjunction with the World Congress of Cardiology (WCC), which took place between 29th August–1st September 2025 in Madrid, Spain. The presentations described analyses of MAPLE-HCM, a Phase III, head-to-head, comparative efficacy and safety study evaluating aficamten versus metoprolol as monotherapy in adults with symptomatic obstructive hypertrophic cardiomyopathy (oHCM). Pablo Garcia-Pavia, Hospital Universitario Puerta de Hierro, Madrid; and Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain, presented the primary and secondary outcomes of MAPLE-HCM, showing that 24 weeks of aficamten led to significant and clinically meaningful improvements in exercise capacity, symptoms, left ventricular outflow tract (LVOT) gradient after the Valsalva manoeuvre, N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels, and structural cardiac remodelling. By contrast, metoprolol led to a reduction in the exercise capacity of these patients and, despite demonstrating on-target haemodynamic effects, failed to reduce LVOT gradients either at rest or following the Valsalva manoeuvre. Sheila Hegde, University of Texas, Southwestern Medical Centre, Dallas, USA; and Brigham and Women’s Hospital, Boston, Massachusetts, USA, presented further substantial improvements in multiple measures of cardiac structure and function with aficamten versus metoprolol. Overall, MAPLE-HCM data highlight the superior efficacy of aficamten over metoprolol, while maintaining an acceptable safety profile. These results strengthen the positioning of aficamten as monotherapy or potential first-line therapy for patients with symptomatic oHCM.