JACC Heart Fail. 2026 Aug 29:103352. doi: 10.1016/j.jchf.2026.103352. Online ahead of print.
ABSTRACT
BACKGROUND: The MAPLE-HCM trial demonstrated the superiority of monotherapy with aficamten vs metoprolol at improving clinical endpoints in obstructive hypertrophic cardiomyopathy (oHCM). The impact of pretrial use of standard-of-care (SOC) medications, including beta-blockers (BBs), was unknown.
OBJECTIVES: The aim of this study was to evaluate the efficacy of aficamten by pretrial medical therapy.
METHODS: Participants were randomized to aficamten (5-20 mg/d) or metoprolol (50-200 mg/d) for 24 weeks. Exercise capacity and other efficacy endpoints were examined by pretrial medical therapy: 1) BB-no: participants not receiving any BB therapy at screening; 2) BB-yes: participants on BB at screening, regardless of duration of exposure; and 3) SOC-no: participants without SOC therapy for ≥12 months before screening. Groups 1 and 3 overlapped, as all SOC-no participants were also included in the BB-no group.
RESULTS: A total of 175 patients were randomized. At screening, 52 participants were BB-no, 123 BB-yes, and 22 SOC-no. The overall mean age was 58 years; 41.7% of patients were women. The mean left ventricular outflow tract gradient was 47 mm Hg at rest and 74 mm Hg after the Valsalva maneuver. Aficamten demonstrated consistent benefits across multiple efficacy endpoints compared with metoprolol, independent of pretrial medical therapy. Aficamten improved exercise capacity (peak oxygen uptake) compared with metoprolol: BB-no: +3.1 mL/kg/min (95% CI: 1.8-4.5 mL/kg/min; P < 0.001); BB-yes: +1.9 mL/kg/min (95% CI: 0.9-2.8 mL/kg/min; P < 0.001) (P for interaction = 0.133); and SOC-no: +4.1 mL/kg/min (95% CI: 2.2-6.0 mL/kg/min; P < 0.001).
CONCLUSIONS: Aficamten was superior to metoprolol regardless of BB use at screening or prior SOC medications. This supports the primary study results and suggests no confounding by BB resistance. Consequently, aficamten can be considered an early treatment option independent of prior SOC history. (Phase 3 Trial to Evaluate the Efficacy and Safety of Aficamten Compared to Metoprolol Succinate in Adults With Symptomatic oHCM [MAPLE-HCM; NCT05767346).
PMID:42667283 | DOI:10.1016/j.jchf.2026.103352