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Aficamten in symptomatic obstructive hypertrophic cardiomyopathy: the FOREST-HCM long-term study

Title: Aficamten in symptomatic obstructive hypertrophic cardiomyopathy: the FOREST-HCM long-term study
Authors: Tower-Rader, Albree; Masri, Ahmad; Nassif, Michael E; Abraham, Theodore P; Barriales-Villa, Roberto; Choudhury, Lubna; Cooper, Robert M; Elliott, Perry M; Maron, Martin S; Olivotto, Iacopo; Oreziak, Artur; Owens, Anjali Tiku; Solomon, Scott D; Heitner, Stephen B; Jacoby, Daniel L; Kupfer, Stuart; Liu, Xueli; Malik, Fady I; Melloni, Chiara; Simkins, Tyrell J; Wei, Jenny; Saberi, Sara
Contributors: Cytokinetics; Incorporated
Source: European Heart Journal ; ISSN 0195-668X 1522-9645
Publisher Information: Oxford University Press (OUP)
Publication Year: 2026
Description: Background and Aims Aficamten is a next-in-class, oral selective cardiac myosin inhibitor that ameliorates hypercontractility in hypertrophic cardiomyopathy (HCM). This study assessed the safety and efficacy of extended aficamten treatment in symptomatic obstructive HCM (oHCM). Methods Patients completing a parent aficamten study were eligible to enrol in FOREST-HCM (NCT04848506), an open-label study evaluating long-term aficamten treatment. Results Patients with oHCM (N = 296; mean age ±SD 61 ± 12.3 years, 44.3% female) enrolled between May 2021 and August 2024. Cumulative exposure was 352 patient-years; median follow-up 51.6 (IQR 41.5, 70.8) weeks. At Weeks 12 and 96, aficamten reduced Valsalva left ventricular outflow tract gradient by 56 ± 43 and 62 ± 33 mmHg from baseline (both P < 0.0001), with minimal reduction in left ventricular ejection fraction (LVEF) (−3% ± 6% and −5% ± 5%); 69% and 93% of participants had at least one NYHA class improvement; Kansas City Cardiomyopathy Questionnaire–Clinical Summary Score improved by 15 ± 16 and 16 ± 16 points. Treatment-emergent serious adverse events (TESAEs) occurred in 36 (12.2%) patients; no deaths, heart failure, or events considered related to aficamten were reported. One (0.3%) patient terminated therapy due to a TESAE (ischemic colitis). LVEF
Document Type: article in journal/newspaper
Language: English
DOI: 10.1093/eurheartj/ehaf1085
DOI: 10.1093/eurheartj/ehaf1085/67228699/ehaf1085.pdf
Availability: https://doi.org/10.1093/eurheartj/ehaf1085; https://academic.oup.com/eurheartj/advance-article-pdf/doi/10.1093/eurheartj/ehaf1085/67228699/ehaf1085.pdf
Rights: https://creativecommons.org/licenses/by/4.0/
Accession Number: edsbas.BFB4B7F4
Database: BASE