Abstract 4142906: Efficacy and Safety of Aficamten in Patients Guideline-Eligible for Septal Reduction Therapy in the FOREST-HCM Trial

Background: Patients (pts) with obstructive hypertrophic cardiomyopathy (oHCM) with severe symptoms despite medical therapy are offered septal reduction therapy (SRT) when available. We report the efficacy and safety of aficamten in SRT-eligible pts in the Phase 2 open-label extension trial FOREST-HCM (NCT04848506). Methods: Pts completing an aficamten parent study were offered participation in FOREST-HCM. Aficamten was initiated in all participants at 5 mg and escalated (10, 15, and 20 mg) at investigators’ discretion with protocol guidance according to left ventricular ejection fraction (LVEF) and left ventricular outflow obstruction (LVOT) criteria. SRT eligibility was defined per guidelines as both New York Heart Association (NYHA) class III/IV and any peak LVOT-G ≥50 mmHg. Results: Of 180 oHCM pts (mean age 60.8±13.1 years, 54% male) enrolled in FOREST-HCM from May 28, 2021 to March 15, 2024 with ≥24 weeks of follow-up, 57 (31.6%) were SRT-eligible at baseline. By week 24, only 2 (3.5%) pts remained SRT eligible (32 [56.1%] met neither criteria, 20 [35.1%] had LVOT-G ≥50 mmHg but were NYHA class I/II, and 2 (3.5%) had NYHA III/IV but LVOT-G <50 mmHg). NYHA improved ≥1 class in 52 (92.9%) SRT-eligible pts and in 80 (67.8%) pts of the remaining cohort. Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CSS) improved more in SRT-eligible pts than remaining cohort (21.7±19.3 vs 13.5±13.9; p=0.003) {Figure}. Proportional reductions from baseline in NT-proBNP and high-sensitivity troponin were substantial in both groups. A modest reduction in LVEF occurred in both groups (-3.6% ±6.4 vs -3.4% ±6.2 in the SRT-eligible and remaining cohort respectively; between group p=0.34) {Figure}. Conclusions: A third of pts enrolled in FOREST-HCM were guideline SRT-eligible at baseline despite optimized standard of care therapy, with almost all pts no longer meeting SRT-eligibility criteria by 24 weeks with aficamten treatment. Aficamten may provide an effective alternative to SRT in some patients with oHCM.

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Journal
Circulation
Published
2024-11-12
DOI
https://doi.org/10.1161/circ.150.suppl_1.4142906
Primary Topic
Cardiovascular Function and Risk Factors
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article
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article

Abstract 4142906: Efficacy and Safety of Aficamten in Patients Guideline-Eligible for Septal Reduction Therapy in the FOREST-HCM Trial

Sherif F. Nagueh, Omar Wever‐Pinzon, Roberto Barriales‐Villa, Perry Elliott et al.
Circulation
Cardiovascular Function and Risk Factors
article

Abstract 4142906: Efficacy and Safety of Aficamten in Patients Guideline-Eligible for Septal Reduction Therapy in the FOREST-HCM Trial

Sherif F. Nagueh, Omar Wever‐Pinzon, Roberto Barriales‐Villa, Perry Elliott, Artur Oręziak, Stephen B. Heitner, Albree Tower Rader, Sara Saberi, Iacopo Olivotto, Ozlem Bilen, Jenny Wei, ANJALI TIKU OWENS, Chiara Melloni, Albert Hagège, Srihari S. Naidu, Pablo García‐Pavía, Ahmad Masri, Fady I. Malik, Stuart Kupfer, Lubna Choudhury, Michael E. Nassif, Lixin Meng, Theodore P. Abraham
article en

Abstract

Background: Patients (pts) with obstructive hypertrophic cardiomyopathy (oHCM) with severe symptoms despite medical therapy are offered septal reduction therapy (SRT) when available. We report the efficacy and safety of aficamten in SRT-eligible pts in the Phase 2 open-label extension trial FOREST-HCM (NCT04848506). Methods: Pts completing an aficamten parent study were offered participation in FOREST-HCM. Aficamten was initiated in all participants at 5 mg and escalated (10, 15, and 20 mg) at investigators’ discretion with protocol guidance according to left ventricular ejection fraction (LVEF) and left ventricular outflow obstruction (LVOT) criteria. SRT eligibility was defined per guidelines as both New York Heart Association (NYHA) class III/IV and any peak LVOT-G ≥50 mmHg. Results: Of 180 oHCM pts (mean age 60.8±13.1 years, 54% male) enrolled in FOREST-HCM from May 28, 2021 to March 15, 2024 with ≥24 weeks of follow-up, 57 (31.6%) were SRT-eligible at baseline. By week 24, only 2 (3.5%) pts remained SRT eligible (32 [56.1%] met neither criteria, 20 [35.1%] had LVOT-G ≥50 mmHg but were NYHA class I/II, and 2 (3.5%) had NYHA III/IV but LVOT-G <50 mmHg). NYHA improved ≥1 class in 52 (92.9%) SRT-eligible pts and in 80 (67.8%) pts of the remaining cohort. Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CSS) improved more in SRT-eligible pts than remaining cohort (21.7±19.3 vs 13.5±13.9; p=0.003) {Figure}. Proportional reductions from baseline in NT-proBNP and high-sensitivity troponin were substantial in both groups. A modest reduction in LVEF occurred in both groups (-3.6% ±6.4 vs -3.4% ±6.2 in the SRT-eligible and remaining cohort respectively; between group p=0.34) {Figure}. Conclusions: A third of pts enrolled in FOREST-HCM were guideline SRT-eligible at baseline despite optimized standard of care therapy, with almost all pts no longer meeting SRT-eligibility criteria by 24 weeks with aficamten treatment. Aficamten may provide an effective alternative to SRT in some patients with oHCM.

CirculationVol. 150(Suppl_1)
Northwestern University (US), Houston Methodist (US), Westchester Medical Center (US), Emory University (US), University of California, San Francisco (US), New York Medical College (US), University of Utah (US), University of Michigan (US), William Penn University (US), British Heart Foundation (GB), Massachusetts General Hospital (US), Centro de Investigación en Red en Enfermedades Cardiovasculares (ES), Assistance Publique – Hôpitaux de Paris (FR), Hôpital Européen Georges-Pompidou (FR), Hôpital Européen (FR), Michigan United (US), Meyer Children's Hospital (IT), Institute of Cardiology (PL), Saint Luke's Hospital (US), Cytokinetics (United States) (US), Complexo Hospitalario Universitario A Coruña (ES), Oregon Health and Science University Hospital (US), Istituti di Ricovero e Cura a Carattere Scientifico (IT), University College London (GB)
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Cardiovascular Function and Risk Factors
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