Abstract Body (Do not enter title and authors here): Background: A primary goal in treating obstructive hypertrophic cardiomyopathy (oHCM) is to improve patients’ health status. Aficamten, a cardiac myosin inhibitor, was recently shown to be superior to improve exercise tolerance and symptoms compared with metoprolol (MAPLE-HCM). The extent to which aficamten improves patients’ health status relative to metoprolol remains incompletely characterized.
Purpose: To compare changes in the Kansas City Cardiomyopathy Overall Summary Score (KCCQ-OSS) and Seattle Angina Questionnaire Summary Score (SAQ-SS) after 24 weeks of monotherapy with aficamten or metoprolol.
Methods: MAPLE-HCM (NCT05767346), an international, multi-center, double-blind trial, randomizing adults with symptomatic oHCM (KCCQ- Clinical Summary ≤ 90); LVOT obstruction ≥30 rest and/or ≥50 mm Hg Valsalva) to aficamten or metoprolol for 24 weeks. The KCCQ and SAQ were administered serially throughout the trial. Changes in mean KCCQ-OSS and SAQ-SS over 24 weeks were compared using linear regression, adjusted for randomization strata and baseline scores. Individual patient experiences were categorized by the magnitude of clinical changes from score ranges: ≤-5 (worse clinical change), >-5 to <5 (no clinical change), 5 to <10 (small clinical improvement), 10 to <15 (moderate clinical improvement), 15 to <20 (large clinical improvement), and ≥20 points (very large clinical improvement).
Results: Among 175 randomized participants (88 aficamten, 87 metoprolol), baseline health status scores were similar. Aficamten was associated with a greater 24-week improvement in KCCQ-OSS (adjusted between-group difference: +7.8 points; 95% CI 3.3, 12.3; p<0.001; Figure 1A). This mean difference between treatments was primarily driven by a combination of a much larger proportion of aficamten treated patients experiencing very large clinical benefits (≥20-point KCCQ-OSS improvement) as compared with metoprolol (38.6% vs 18.4%, number needed to treat = 5) and a much smaller proportion experiencing worsening (≤-5-point KCCQ-OSS worsening) versus metoprolol (6.8% vs 18.4%, number needed to harm = 8.6). A trend for greater SAQ-SS improvement with aficamten (4.6 [95% CI: -0.3, 9.5]; p=0.063) was driven by a significant improvement in physical limitations (SAQ-PL, 10.1 [95% CI: 4.1, 16.2]; p=0.001).
Conclusions: Aficamten improves the health status of patients with symptomatic oHCM significantly more than metoprolol, supporting its potential use as first-line treatment in oHCM.