Cardiac myosin activation with omecamtiv mecarbil in systolic heart failure

for the GALACTIC-HF Investigators, John R. Teerlink, Rafael Díaz, G. Michael Felker, John J.V. McMurray, Marco Metra, Scott D. Solomon, Kirkwood F. Adams, Inder Anand, Alexandra Arias-Mendoza, Tor Biering-Sorensen, Michael Böhm, Diana Bonderman, John G.F. Cleland, Ramon Corbalan, Maria G. Crespo-Leiro, Ulf Dahlström, Luis E. Echeverria, James C. Fang, Gerasimos FilippatosCandida Fonseca, Eva Goncalvesova, Assen R. Goudev, Jonathan G. Howlett, David E. Lanfear, Jing Li, Mayanna Lund, Peter MacDonald, Viacheslav Mareev, Shin Ichi Momomura, Eileen O'Meara, Alexander Parkhomenko, Piotr Ponikowski, Felix J.A. Ramires, 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, Beat Knusel, Thomas Hucko, John Groarke, Marvin A. Konstam, Javed Butler, Henry Dargie, Joseph Massaro, Barry H. Greenberg, James L. Januzzi, Lawrence J. Lesko, Jenica N. Upshaw, Renato Lopes, W. Schuyler Jones, Karen P. Alexander, Sana M. Al-Khatib, Robert W. Harrison, J. Dedrick Jordan, David F. Kong, Robin Mathews, Robert W. McGarrah, Rajendra H. Metha, Chiara Melloni, Thomas J. Povsic, Shreyansh Shah, Brian Claggett, Alexandra Arias Mendoza, Tor Biering-Sørensen, Marisa Crespo Leiro, Lixin Jiang, Diego Alejandro Besada, Claudio Rodolfo Majul, Marcos Raul Litvak Bruno, Sonia Sassone, Horacio Alberto Avaca, Mariela Rasmussen, Jorge Roberto Aiub, Miguel Angel Hominal, Eduardo Perna, Ruben Omar Garcia Duran, Lilia Schiavi, Lilia Luz Lobo Marquez, Oscar Alberto Gomez Vilamajo, Ignacio MacKinnon, Ricardo Alfonso Leon De La Fuente, Oscar Romano Montana, Leonardo Novaretto, Rodolfo Andres Ahuad Guerrero, Daniela Garcia Brasca, Aldo Prado, Marcelo Alejandro Garrido, Hugo Luquez, Diego Felipe Martinez, Liliana Nicolosi, Maria Leonor Parody, Cesar Zaidman, Fernando Colombo Berra, Julio Ibañez, Gerardo Zapata, Marcos Amuchastegui, Alberto Caccavo, Roberto Colque, Mirta Diez, Carlos Poy, Oscar Alejandro Salomone, Daniel Vogel, Anselmo Paulino Bordonava, Alberto Fernandez, John French, John Atherton, Andrew Hamilton, Alistair Begg, Walter Abhayaratna, Christopher Judkins, Peter MacDonald, Carmine De Pasquale, Scott McKenzie, John Amerena, Gregory Szto, Leighton Kearney, Hendrik Zimmet, Aaron Sverdlov, John Beltrame, Dariusz Korczyk, Andrew Sindone, Deddo Moertl, Kurt Huber, Martin Huelsmann, Gabriele Jakl-Kotauschek, Klemens Ablasser, Friedrich Fruhwald, Christian Ebner, Peter Siostrzonek, Heinz Drexel, Gerhard Poelzl, Karl Dujardin, Matthias Dupont, Ian Buysschaert, Patrizio Lancellotti, Luc Pierard, Hans Vandekerckhove, Walter Droogne, Iman Chouchane, Fabio Silveira, Salvador Rassi, Gilmar Reis, Pedro Pimentel Filho, Marcus Vinicius Simoes, Joao Carlos Braga, Flavio Eduardo Giorgeto, Norberto Duda, Almir Ferraz, Cristiano Pederneiras Jaeger, Rafael Luiz Rech, Jose Francisco Saraiva, Alexandre Tognon, Juliano Cardoso, Oswaldo Greco, Maria Sanali Paiva, Bruno Paolino, Otavio Coelho Filho, Lilia Nigro Maia, Rodrigo Da Silva, Manoel Canesin, Paulo Roberto Ferreira Rossi, Lidia Ana Zytynski Moura, Jose Augusto Ribas Fortes, Rodrigo Julio Cerci, Euler Roberto Fernandes Manenti, Paulo Ernesto Leaes, Luis Beck Da Silva Neto, Weimar Kunz Barroso De Souza, Fernando Bacal, Renato Chaves, Felix Ramires, Maria Helena Vidotti, Flavio Brito, Pedro Gabriel Melo De Barros E Silva, Leopoldo Soares Piegas, Georgi Todorov, Maria Tzekova, Assen Goudev, Valentina Mincheva, Aleksandra Manolova, Ivaylo Vasilev, Snezhanka Tisheva-Gospodinova, Ivo Petrov, Arman Postadzhiyan, Edward Geltman, Daniel Lenihan, Thomas Duythuc To

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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 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.).

Original languageEnglish
Pages (from-to)105-116
Number of pages12
JournalNew England Journal of Medicine
Volume384
Issue number2
DOIs
StatePublished - Jan 14 2021

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