• N. Engl. J. Med. · Jan 2021

    Randomized Controlled Trial Multicenter Study

    Cardiac Myosin Activation with Omecamtiv Mecarbil in Systolic Heart Failure.

    • John R Teerlink, Rafael Diaz, G Michael Felker, McMurrayJohn J VJJV0000-0002-6317-3975From the Section of Cardiology, San Francisco Veterans Affairs Medical Center and School of Medicine, University of California, San Francisco, San Francisco (J.R.T.), Amgen, Thousand Oaks (L.S., J.C.L., N.H., S.A.A., , Marco Metra, Scott D Solomon, Kirkwood F Adams, Inder Anand, Alexandra Arias-Mendoza, Tor Biering-Sørensen, Michael Böhm, Diana Bonderman, ClelandJohn G FJGFFrom the Section of Cardiology, San Francisco Veterans Affairs Medical Center and School of Medicine, University of California, San Francisco, San Francisco (J.R.T.), Amgen, Thousand Oaks (L.S., J.C.L., N.H., S.A.A., C.E.K.), and Cytokin, Ramon Corbalan, Maria G Crespo-Leiro, Ulf Dahlström, Luis E Echeverria, James C Fang, Gerasimos Filippatos, Cândida Fonseca, Eva Goncalvesova, Assen R Goudev, Jonathan G Howlett, David E Lanfear, Jing Li, Mayanna Lund, Peter Macdonald, Viacheslav Mareev, MomomuraShin-IchiSIFrom the Section of Cardiology, San Francisco Veterans Affairs Medical Center and School of Medicine, University of California, San Francisco, San Francisco (J.R.T.), Amgen, Thousand Oaks (L.S., J.C.L., N.H., S.A.A., C.E.K.), and Cytoki, Eileen O'Meara, Alexander Parkhomenko, Piotr Ponikowski, RamiresFelix J AFJAFrom the Section of Cardiology, San Francisco Veterans Affairs Medical Center and School of Medicine, University of California, San Francisco, San Francisco (J.R.T.), Amgen, Thousand Oaks (L.S., J.C.L., N.H., S.A.A., C.E.K.), and Cytoki, Pranas Serpytis, Karen Sliwa, Jindrich Spinar, Thomas M Suter, Janos Tomcsanyi, Hans Vandekerckhove, Dragos Vinereanu, Adriaan A Voors, Mehmet B Yilmaz, Faiez Zannad, Lucie Sharpsten, Jason C Legg, Claire Varin, Narimon Honarpour, Siddique A Abbasi, Fady I Malik, Christopher E Kurtz, and GALACTIC-HF Investigators.
    • From the Section of Cardiology, San Francisco Veterans Affairs Medical Center and School of Medicine, University of California, San Francisco, San Francisco (J.R.T.), Amgen, Thousand Oaks (L.S., J.C.L., N.H., S.A.A., C.E.K.), and Cytokinetics, South San Francisco (F.I.M.) - all in California; Estudios Clínicos Latino América, Rosario, Argentina (R.D.); the Division of Cardiology, Duke University School of Medicine and Duke Clinical Research Institute, Durham (G.M.F.), and the University of North Carolina, Chapel Hill (K.F.A.) - both in North Carolina; the British Heart Foundation Cardiovascular Research Centre (J.J.V.M.) and the Robertson Centre for Biostatistics and Clinical Trials, Institute of Health and Wellbeing (J.G.F.C.), University of Glasgow, Glasgow, and the National Heart and Lung Institute, Imperial College, London (J.G.F.C.) - both in the United Kingdom; Cardiology, ASST Spedali Civili, Department of Medical and Surgical Specialties, Radiologic Sciences, and Public Health, University of Brescia, Brescia, Italy (M.M.); the Division of Cardiovascular Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston (S.D.S.); the University of Minnesota, Minneapolis (I.A.); Instituto Nacional de Cardiología, Mexico City (A.A.-M.); the Department of Cardiology, Herlev and Gentofte Hospital, and the Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen (T.B.-S.); Saarland University, Universitätsklinikum des Saarlandes, Homburg, Germany (M.B.); Medical University of Vienna, Vienna (D.B.); Pontificia Universidad Católica de Chile, Santiago (R.C.); Complexo Hospitalario Universitario A Coruña, Centro de Investigación Biomédica en Red, Enfermedades Cardiovasculares, Instituto de Investigación Biomédica de A Coruña, Universidade da Coruña, A Coruña, Spain (M.G.C.-L.); the Departments of Cardiology and Health, Medicine and Caring Sciences, Linkoping University, Linkoping, Sweden (U.D.); Fundación Cardiovascular de Colombia, Floridablanca, Colombia (L.E.E.); University of Utah, Salt Lake City (J.C.F.); National and Kapodistrian University of Athens, Attikon University Hospital, Athens (G.F.); Hospital S. Francisco Xavier, Centro Hospitalar Lisboa Ocidental, NOVA Medical School, Faculdade de Ciências Médicas, Universidade Nova de Lisboa, Lisbon, Portugal (C.F.); Commenius University, Bratislava, Slovakia (E.G.); the Department of Cardiology, Queen Giovanna University Hospital and Medical University, Sofia, Bulgaria (A.R.G.); Libin Cardiovascular Institute and Cumming School of Medicine, University of Calgary, Calgary, AB (J.G.H.), and Montreal Heart Institute and Université de Montréal, Montreal (E.O.) - both in Canada; the Heart and Vascular Institute, Henry Ford Hospital, Detroit (D.E.L.); the National Clinical Research Center for Cardiovascular Diseases, National Health Commission Key Laboratory of Clinical Research for Cardiovascular Medications, Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing (J.L.); Middlemore Hospital, Otahuhu, Auckland, New Zealand (M.L.); St. Vincent's Hospital Sydney, Darlinghurst, NSW, Australia (P.M.); University Clinic of Lomonosov, Moscow State University, Moscow (V.M.); Saitama Citizens Medical Center, Saitama, Japan (S.M.); Institute of Cardiology, Kyiv, Ukraine (A.P.); Wroclaw Medical University, Wroclaw, Poland (P.P.); Instituto do Coração, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, Faculdade de Medicina, Universidade de São Paulo, São Paulo (F.J.A.R.); Vilnius University, Vilnius, Lithuania (P.S.); the University of Cape Town, Cape Town, South Africa (K.S.); the Internal Cardiology Department, St. Ann Hospital and Masaryk University Brno, Brno, Czech Republic (J.S.); the Department of Cardiology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland (T.M.S.); St. John of God Hospital, Budapest, Hungary (J.T.); AZ Sint-Lucas, Ghent, Belgium (H.V.); the University of Medicine and Pharmacy Carol Davila, University and Emergency Hospital, Bucharest, Romania (D.V.); the University of Groningen, Groningen, the Netherlands (A.A.V.); Dokuz Eylul University, Izmir, Turkey (M.B.Y.); and Université de Lorraine, INSERM Investigation Network Initiative Cardiovascular and Renal Clinical Trialists, Centre Hospitalier Régional Universitaire de Nancy, Nancy (F.Z.), and Servier, Suresnes (C.V.) - both in France.
    • N. Engl. J. Med. 2021 Jan 14; 384 (2): 105-116.

    BackgroundThe selective cardiac myosin activator omecamtiv mecarbil has been shown to improve cardiac function in patients with heart failure with a reduced ejection fraction. Its effect on cardiovascular outcomes is unknown.MethodsWe randomly assigned 8256 patients (inpatients and outpatients) with symptomatic chronic heart failure and an ejection fraction of 35% or less to receive omecamtiv mecarbil (using pharmacokinetic-guided doses of 25 mg, 37.5 mg, or 50 mg twice daily) or placebo, in addition to standard heart-failure therapy. The primary outcome was a composite of a first heart-failure event (hospitalization or urgent visit for heart failure) or death from cardiovascular causes.ResultsDuring a median of 21.8 months, a primary-outcome event occurred in 1523 of 4120 patients (37.0%) in the omecamtiv mecarbil group and in 1607 of 4112 patients (39.1%) in the placebo group (hazard ratio, 0.92; 95% confidence interval [CI], 0.86 to 0.99; P = 0.03). A total of 808 patients (19.6%) and 798 patients (19.4%), respectively, died from cardiovascular causes (hazard ratio, 1.01; 95% CI, 0.92 to 1.11). There was no significant difference between groups in the change from baseline on the Kansas City Cardiomyopathy Questionnaire total symptom score. At week 24, the change from baseline for the median N-terminal pro-B-type natriuretic peptide level was 10% lower in the omecamtiv mecarbil group than in the placebo group; the median cardiac troponin I level was 4 ng per liter higher. The frequency of cardiac ischemic and ventricular arrhythmia events was similar in the two groups.ConclusionsAmong patients with heart failure and a reduced ejection, those who received omecamtiv mecarbil had a lower incidence of a composite of a heart-failure event or death from cardiovascular causes than those who received placebo. (Funded by Amgen and others; GALACTIC-HF ClinicalTrials.gov number, NCT02929329; EudraCT number, 2016-002299-28.).Copyright © 2020 Massachusetts Medical Society.

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