John R Teerlink1, Rafael Diaz1, G Michael Felker1, John J V McMurray1, Marco Metra1, Scott D Solomon1, Kirkwood F Adams1, Inder Anand1, Alexandra Arias-Mendoza1, Tor Biering-Sørensen1, Michael Böhm1, Diana Bonderman1, John G F Cleland1, Ramon Corbalan1, Maria G Crespo-Leiro1, Ulf Dahlström1, Luis E Echeverria1, James C Fang1, Gerasimos Filippatos1, Cândida Fonseca1, Eva Goncalvesova1, Assen R Goudev1, Jonathan G Howlett1, David E Lanfear1, Jing Li1, Mayanna Lund1, Peter Macdonald1, Viacheslav Mareev1, Shin-Ichi Momomura1, Eileen O'Meara1, Alexander Parkhomenko1, Piotr Ponikowski1, Felix J A Ramires1, Pranas Serpytis1, Karen Sliwa1, Jindrich Spinar1, Thomas M Suter1, Janos Tomcsanyi1, Hans Vandekerckhove1, Dragos Vinereanu1, Adriaan A Voors1, Mehmet B Yilmaz1, Faiez Zannad1, Lucie Sharpsten1, Jason C Legg1, Claire Varin1, Narimon Honarpour1, Siddique A Abbasi1, Fady I Malik1, Christopher E Kurtz1. 1. 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.
Abstract
BACKGROUND: The 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. METHODS: We randomly assigned 8256 patients (inpatients and outpatients) with symptomatic chronic heart failure and an ejection fraction of 35% or less to receiveomecamtiv 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. RESULTS: During 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 CardiomyopathyQuestionnaire 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. CONCLUSIONS: Among 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.).
RCT Entities:
BACKGROUND: The 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. METHODS: We 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. RESULTS: During 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. CONCLUSIONS: Among 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.).
Authors: Fabiana G Marcondes-Braga; Lídia Ana Zytynski Moura; Victor Sarli Issa; Jefferson Luis Vieira; Luis Eduardo Rohde; Marcus Vinícius Simões; Miguel Morita Fernandes-Silva; Salvador Rassi; Silvia Marinho Martins Alves; Denilson Campos de Albuquerque; Dirceu Rodrigues de Almeida; Edimar Alcides Bocchi; Felix José Alvarez Ramires; Fernando Bacal; João Manoel Rossi Neto; Luiz Claudio Danzmann; Marcelo Westerlund Montera; Mucio Tavares de Oliveira Junior; Nadine Clausell; Odilson Marcos Silvestre; Reinaldo Bulgarelli Bestetti; Sabrina Bernadez-Pereira; Aguinaldo F Freitas; Andréia Biolo; Antonio Carlos Pereira Barretto; Antônio José Lagoeiro Jorge; Bruno Biselli; Carlos Eduardo Lucena Montenegro; Edval Gomes Dos Santos Júnior; Estêvão Lanna Figueiredo; Fábio Fernandes; Fabio Serra Silveira; Fernando Antibas Atik; Flávio de Souza Brito; Germano Emílio Conceição Souza; Gustavo Calado de Aguiar Ribeiro; Humberto Villacorta; João David de Souza Neto; Livia Adams Goldraich; Luís Beck-da-Silva; Manoel Fernandes Canesin; Marcelo Imbroinise Bittencourt; Marcely Gimenes Bonatto; Maria da Consolação Vieira Moreira; Mônica Samuel Avila; Otavio Rizzi Coelho Filho; Pedro Vellosa Schwartzmann; Ricardo Mourilhe-Rocha; Sandrigo Mangini; Silvia Moreira Ayub Ferreira; José Albuquerque de Figueiredo Neto; Evandro Tinoco Mesquita Journal: Arq Bras Cardiol Date: 2021-06 Impact factor: 2.000
Authors: Amr Abdin; Johann Bauersachs; Norbert Frey; Ingrid Kindermann; Andreas Link; Nikolaus Marx; Mitja Lainscak; Jonathan Slawik; Christian Werner; Jan Wintrich; Michael Böhm Journal: Clin Res Cardiol Date: 2021-05-13 Impact factor: 5.460