Patients with obstructive hypertrophic cardiomyopathy (oHCM) treated with aficamten saw superior benefits in heart failure symptoms, exercise capacity, left ventricular outflow tract (LVOT) gradient and overall health status when compared to metoprolol, according to two analyses of the MAPLE-HCM trial presented at AHA 2025 and simultaneously published in JACC.

The first study looked at five efficacy outcomes related to oHCM disease burden – LVOT gradient <30 mm Hg at rest and <50 mm Hg with Valsalva; ≥1 NYHA class improvement and/or ≥10-point Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CSS) improvement; ≥50% reduction in NT-proBNP; ≥1.0 mL/kg/min increase in peak oxygen consumption; and ≥10% reduction in left atrial volume index. Andrew Wang, MD, FACC, et al., established four clinical response categories by the number of outcomes achieved: nonresponder (0), limited (1-2), positive (3-4) or complete (5).

Including 175 patients (mean age 58, 42% female) with oHCM randomized to 24 weeks of aficamten or metoprolol, the authors found treatment with aficamten was associated with larger improvements in all outcomes measured. Patients in the aficamten treatment group also exhibited a greater likelihood of being in the positive or complete responder classifications vs. those in the metoprolol group (78% vs. 3%; p<0.001).

“Using the most clinically applied measures of beneficial treatment response in treating symptomatic [oHCM], specifically reduction in [LVOT gradient] and improvement in symptoms by NYHA class and/or KCCQ-CSS, a positive response was evident in a substantially higher proportion of patients treated with aficamten than metoprolol and was achieved as early as eight weeks after dose titration,” note the authors.

An additional study focuses further on the patient-reported health status of MAPLE-HCM trial participants.

Michael E. Nassif, MD, FACC, et al., investigated improvements in KCCQ Overall Summary Score (OSS) and Seattle Angina Questionnaire Summary Score (SAQ-SS) among the 175 patients analyzed. They used the following categories to compare participant change in these scores: ≤–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).

The authors observed a greater improvement in KCCQ-OSS among the aficamten treatment group at 24 weeks (adjusted between-group difference: +7.8 points; 95% CI 3.3-12.3; p<0.001), mainly due to a larger number of patients from the aficamten group (38.6%) seeing very large improvement vs. those in the metoprolol group (18.6%). There were also fewer patients in the aficamten group with worse health status (6.8%) vs. the metoprolol group (18.4%).

Although improvements with aficamten vs. metoprolol were also observed with SAQ-SS, these results were not statistically significant (+4.6 [95% CI –0.3-9.5] points; p=0.063).

“In contrast to the KCCQ, where all domains demonstrated significantly more benefit with aficamten compared with metoprolol, more modest, non-statistically significant benefits were seen in the SAQ Angina Frequency scale,” write the authors. “The reason for this discrepancy is unclear and will require further investigation.”

Keywords: AHA Annual Scientific Sessions, AHA25