Aficamten Reduces Eligibility for Septal Reduction Therapy in Obstructive Hypertrophic Cardiomyopathy: Long-Term Outcomes from FOREST-HCM
Abstract
Background: Septal reduction therapy (SRT) is recommended in drug-refractory, symptomatic obstructive hypertrophic cardiomyopathy (oHCM). We evaluated whether aficamten, a novel cardiac myosin inhibitor, can reliably transition guideline-eligible SRT candidates to ineligibility, and the associated safety profile of aficamten in this group.
Methods: We analyzed participants with oHCM enrolled in FOREST-HCM ( NCT04848506 ), the long-term open-label extension study of aficamten, from 28 May 2021 to 9 May 2025.
Results: Three hundred and fifteen patients were included, of whom 104 met 2024 ACC/AHA guideline criteria for SRT eligibility at baseline. The SRT-eligible cohort was predominantly female (57%), with mean resting and Valsalva left ventricular outflow tract (LVOT) gradients of 63 ± 39 and 109 ± 42 mmHg, and all were in New York Heart Association (NYHA) class III. All baseline SRT-eligible patients became SRT-ineligible with aficamten therapy during study follow-up over a median of 42 days (IQR: 17, 49), except for one participant who withdrew from the study to pursue SRT (total of 3 participants withdrew). After dose titration, 3/104 (2.9%) remained guideline-eligible; by week 72 no patients met eligibility criteria. At maintenance, resting and Valsalva LVOT gradients improved by a least-squares mean of −41 mmHg ([95% CI −44 to −37]; P< 0.0001) and −56 mmHg ([95% CI −62 to −51]; P< 0.0001), respectively. Relative to baseline, NT-proBNP improved by 77% (95% CI 74 – 80%),…
How strong is the evidence?
Evidence Hub reads this as a cohort study, done in people. Its evidence level is 3 of 5 (Moderate · trial / cohort / secondary analysis). Trials without a large randomized design, cohorts and secondary analyses give moderate evidence. Reported size: 72 participants or records.
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