Effect of Aficamten vs Metoprolol on Patient-Reported Health Status in Obstructive Hypertrophic Cardiomyopathy

BACKGROUND The cardiac myosin inhibitor aficamten was significantly more effective than metoprolol at improving exercise tolerance in MAPLE-HCM (Metoprolol vs Aficamten in Patients with LVOT Obstruction on Exercise Capacity in HCM), a head-to-head, international, double-blind, randomized trial in patients with obstructive hypertrophic cardiomyopathy (oHCM). Given the primary treatment goal to improve patients' health status, defining the incremental benefits of aficamten over metoprolol on patients' symptoms, function, and quality of life is needed. OBJECTIVES In this study, the authors sought to compare patient-reported health status benefits of aficamten with metoprolol. METHODS Adults with symptomatic oHCM (Kansas City Cardiomyopathy Questionnaire KCCQ Clinical Summary Score CSS ≤90; left ventricular outflow tract obstruction ≥30 mm Hg at rest or ≥50 mm Hg with Valsalva) were randomly assigned to 24 weeks of aficamten or metoprolol as monotherapy. Changes in KCCQ Overall Summary Score (OSS) and Seattle Angina Questionnaire Summary Score (SAQ-SS), collected serially throughout the trial, were compared between treatment groups at 24 weeks using linear regression, adjusted for randomization strata and baseline scores. Individual participant experiences were described by comparing categories of clinically meaningful within-participant change: ≤-5 (worse), >-5 to <+5 (no change), +5 to <+10 (small improvement), +10 to <+15 (moderate improvement), +15 to <+20 (large improvement), and ≥+20 points (very large improvement). RESULTS Among 175 randomized patients, baseline health status scores were similar between treatment groups (n = 88 aficamten; n = 87 metoprolol). Aficamten, compared with metoprolol, resulted in a greater 24-week KCCQ-OSS improvement (adjusted between-group difference: +7.8 points; 95% CI: 3.3-12.3; P < 0.001), primarily driven by a greater proportion of aficamten-treated (38.6%) vs metoprolol-treated (18.4%) patients experiencing a very large (≥20 points) KCCQ-OSS improvement (number needed to treat = 4.9; 95% CI: 3.0-13.9), and a smaller proportion experiencing worsening health status (≤-5-point change: 6.8% vs 18.4%; number needed to harm = 8.6; 95% CI: 4.7-53.3). Nonsignificant SAQ-SS improvements with aficamten vs metoprolol (+4.6 points; 95% CI -0.3 to 9.5 points; P = 0.063) were driven by significantly larger improvements in the SAQ Physical Limitation scale (+10.1 points; 95% CI: 3.9-16.2 points; P = 0.001). CONCLUSIONS Aficamten improved the health status of patients with symptomatic oHCM significantly more than did metoprolol, highlighting its potential as an effective initial therapeutic option. (Phase 3 Trial to Evaluate the Efficacy and Safety of Aficamten Compared to Metoprolol Succinate in Adults With Symptomatic oHCM (MAPLE-HCM; NCT05767346).