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Aficamten for Symptomatic Obstructive Hypertrophic Cardiomyopathy
Martin S Maron1, Ahmad Masri1, Michael E Nassif1
1From Lahey Hospital and Medical Center, Burlington (M.S.M.), and the Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School (B.C., S.D.S.), the Division of Cardiology, Department of Medicine, Massachusetts General Hospital, Harvard Medical School (J.L.J., G.D.L.), and the Baim Institute for Clinical Research (J.L.J.), Boston - all in Massachusetts; Oregon Health and Science University, Portland (A.M.); the University of Missouri Kansas City Healthcare Institute for Innovations in Quality and Saint Luke's Mid America Heart Institute, Kansas City (M.E.N., J.A.S.); Complejo Hospitalario Universitario de A Coruña, Instituto de Investigación Biomédica de A Coruña, Centro de Investigación Biomédica en Red de Enfermedades Cardiovaculares (CIBERCV)-Instituto de Salud Carlos III, A Coruña (R.B.-V.), and Hospital Universitario Puerta de Hierro de Majadahonda, Instituto de Investigación Sanitaria Puerta de Hierro-Segovia de Arana, CIBERCV, and Centro Nacional de Investigaciones Cardiovasculares, Madrid (P.G.-P.) - both in Spain; Chaim Sheba Medical Center, Ramat Gan and Tel Aviv University, Tel Aviv, Israel (M.A.); Hospital Companhia União Fabril Descobertas, Lisbon, Portugal (N.C.); Northwestern University Feinberg School of Medicine, Chicago (L.C.); the School of Cardiovascular and Metabolic Health, University of Glasgow, Glasgow (C.J.C., M.M.Y.L.), and Radcliffe Department of Medicine, University of Oxford, Oxford (H.W.) - both in the United Kingdom; Charité Campus Virchow-Klinikum, Berlin (H.-D.D.); Département de Cardiologie, Hôpital Européen Georges-Pompidou, Assistance Publique-Hôpitaux de Paris, Paris (A.A.H.); Beijing Anzhen Hospital, Capital Medical University, Beijing (C.-S.M.); the Department of Cardiology, Thoraxcenter, Erasmus Medical Center, Rotterdam (M.M.) and Zwolle (M.S.) - both in the Netherlands; Meyer Children's Hospital, Istituto di Ricovero e Cura a Carattere Scientifico, Florence, Italy (I.O.); National Institute of Cardiology, Warsaw, Poland (A.O.); University of Pennsylvania Perelman School of Medicine, Philadelphia (A.T.O.); the Section of Forensic Genetics, Department of Forensic Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, and the Department of Cardiology, Copenhagen University Hospital Rigshospitalet, Copenhagen (J.T.-H.); the Department of Cardiology, Motol University Hospital, Prague, Czech Republic (J.V.); Cytokinetics, South San Francisco (D.L.J., S.B.H., S.K., F.I.M., L.M., A.W.), and the University of California, San Francisco, San Francisco (T.P.A.) - both in California.
Aficamten significantly improved peak oxygen uptake in patients with obstructive hypertrophic cardiomyopathy (HCM). This cardiac myosin inhibitor demonstrated superior efficacy over placebo across all secondary endpoints, enhancing quality of life.
Area of Science:
- Cardiology
- Pharmacology
- Clinical Trials
Background:
- Obstructive hypertrophic cardiomyopathy (HCM) causes exercise intolerance due to elevated intracardiac pressure from left ventricular outflow tract obstruction.
- Aficamten, a selective cardiac myosin inhibitor, targets hypercontractility to reduce left ventricular outflow tract gradients.
Purpose of the Study:
- To evaluate the efficacy and safety of aficamten in patients with symptomatic obstructive HCM.
- To assess the impact of aficamten on exercise capacity and functional status.
Main Methods:
- A phase 3, double-blind trial randomized 282 adults with symptomatic obstructive HCM to aficamten or placebo for 24 weeks.
- The primary endpoint was the change in peak oxygen uptake assessed by cardiopulmonary exercise testing.
- Secondary endpoints included changes in quality of life (KCCQ-CSS), NYHA functional class, and left ventricular outflow tract gradients.
Main Results:
- Aficamten significantly increased peak oxygen uptake by 1.8 ml/kg/min compared to 0.0 ml/kg/min with placebo (P<0.001).
- All 10 prespecified secondary endpoints showed significant improvement with aficamten versus placebo.
- Adverse event incidence was similar between the aficamten and placebo groups.
Conclusions:
- Aficamten treatment led to significantly greater improvements in peak oxygen uptake compared to placebo in patients with symptomatic obstructive HCM.
- Aficamten is an effective therapeutic option for improving exercise capacity and functional status in obstructive HCM.
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