Cardiac Myosin Activation with Omecamtiv Mecarbil in Systolic Heart Failure
John R Teerlink
(1)
,
Rafael Diaz
(2)
,
G. Michael Felker
(3)
,
John J.V. Mcmurray
(4)
,
Marco Metra
(5, 6)
,
Scott D Solomon
(7)
,
Kirkwood F Adams
(8)
,
Inder Anand
(9)
,
Alexandra Arias-Mendoza
(10)
,
Tor Biering-Sørensen
(7, 11)
,
Michael Böhm
(12)
,
Diana Bonderman
(13)
,
John G.F. Cleland
(14, 15)
,
Ramon Corbalan
(16)
,
Maria G Crespo-Leiro
(17)
,
Ulf Dahlström
(18)
,
Luis E Echeverria
(19)
,
James C Fang
(20)
,
Gerasimos Filippatos
(21, 22, 23)
,
Cândida Fonseca
(24, 25)
,
Eva Goncalvesova
(26)
,
Assen R Goudev
(27)
,
Jonathan G Howlett
(28)
,
David E Lanfear
(29)
,
Jing Li
(30)
,
Mayanna Lund
(31)
,
Peter Macdonald
(32)
,
Viacheslav Mareev
(33)
,
Shin-Ichi Momomura
(34)
,
Eileen O’meara
(35, 36)
,
Alexander Parkhomenko
(37)
,
Piotr Ponikowski
(38)
,
Felix J.A. Ramires
(39)
,
Pranas Serpytis
(40)
,
Karen Sliwa
(41)
,
Jindrich Spinar
(42)
,
Thomas M Suter
(43)
,
Janos Tomcsanyi
(44)
,
Hans Vandekerckhove
(45)
,
Dragos Vinereanu
(46)
,
Adriaan A Voors
(47)
,
Mehmet B Yilmaz
(48)
,
Faiez Zannad
(49, 50, 51, 52)
,
Lucie Sharpsten
(53)
,
Jason C Legg
(53)
,
Claire Varin
(54)
,
Narimon Honarpour
(53)
,
Siddique A Abbasi
(53)
,
Fady I Malik
(55)
,
Christopher E Kurtz
(1, 53)
1
Veterans Affairs Medical Center, San Francisco, California
2 Estudios Clinicos Latino America (ECLA)
3 Duke Clinical Research Institute
4 BHF GCRC - British Heart Foundation Glasgow Cardiovascular Research Centre
5 UniBs - Università degli Studi di Brescia = University of Brescia
6 Civic Hospital of Brescia
7 BWH - Brigham & Women’s Hospital [Boston]
8 Department Biostatistics University of North Carolina
9 University of Minnesota Medical School
10 National Institute of Cardiology, Mexico City
11 Herlev and Gentofte Hospital
12 Universität des Saarlandes [Saarbrücken] = Saarland University [Saarbrücken]
13 Medizinische Universität Wien = Medical University of Vienna
14 University of Glasgow
15 NHLI - National Heart and Lung Institute [London]
16 UC - Pontificia Universidad Católica de Chile
17 UDC - University of A Coruña
18 LIU - Linköping University
19 Fundación Cardiovascular de Colombia [Floridablanca]
20 University of Utah
21 NKUA - National and Kapodistrian University of Athens
22 UOA - Université d'Athènes
23 “Attikon” University Hospital
24 EPE - Hospital de S. Francisco Xavier
25 NOVA - Universidade Nova de Lisboa = NOVA University Lisbon
26 Commenius University in Bratislava - Univerzita Komenského
27 EAS - European Atherosclerosis Society [Göteborg, Sweden]
28 University of Calgary
29 Henry Ford Hospital
30 CATAS - Chinese Academy of Tropical Agricultural Sciences
31 Middlemore Hospital
32 St. Vincent's Hospital, Sydney
33 MSU - Lomonosov Moscow State University = Université d'État Lomonossov de Moscou [Moscou]
34 Saitama Citizens Medical Center
35 Montreal Heart Institute - Institut de Cardiologie de Montréal
36 UdeM - Université de Montréal
37 NSC/MDSIC - National Scientific Center "M.D. Strazhesko Institute of Cardiology" [Kyiv, Ukraine]
38 Wrocław Medical University
39 USP - Universidade de São Paulo = University of São Paulo
40 Vilnius University [Vilnius]
41 University of Cape Town
42 MUNI - Masaryk University [Brno]
43 Inselspital - Bern University Hospital [Berne]
44 Saint John of God Clinical Research Centre
45 AZ Sint-Lucas
46 UMPCD - University of Medicine and Pharmacy “Carol Davila”
47 University of Groningen [Groningen]
48 DEÜ - Dokuz Eylül Üniversitesi = Dokuz Eylül University [Izmir]
49 DCAC - Défaillance Cardiovasculaire Aiguë et Chronique
50 CIC-P - Centre d'investigation clinique plurithématique Pierre Drouin [Nancy]
51 INI-CRCT - Cardiovascular and Renal Clinical Trialists [Vandoeuvre-les-Nancy]
52 Cardiovascular & Renal Clinical Trialists - CRCT - French-Clinical Research Infrastructure Network - F-CRIN [Paris]
53 AMGen - Applied Molecular Genetics
54 Laboratoire Servier
55 CI - Cytokinetics Inc
2 Estudios Clinicos Latino America (ECLA)
3 Duke Clinical Research Institute
4 BHF GCRC - British Heart Foundation Glasgow Cardiovascular Research Centre
5 UniBs - Università degli Studi di Brescia = University of Brescia
6 Civic Hospital of Brescia
7 BWH - Brigham & Women’s Hospital [Boston]
8 Department Biostatistics University of North Carolina
9 University of Minnesota Medical School
10 National Institute of Cardiology, Mexico City
11 Herlev and Gentofte Hospital
12 Universität des Saarlandes [Saarbrücken] = Saarland University [Saarbrücken]
13 Medizinische Universität Wien = Medical University of Vienna
14 University of Glasgow
15 NHLI - National Heart and Lung Institute [London]
16 UC - Pontificia Universidad Católica de Chile
17 UDC - University of A Coruña
18 LIU - Linköping University
19 Fundación Cardiovascular de Colombia [Floridablanca]
20 University of Utah
21 NKUA - National and Kapodistrian University of Athens
22 UOA - Université d'Athènes
23 “Attikon” University Hospital
24 EPE - Hospital de S. Francisco Xavier
25 NOVA - Universidade Nova de Lisboa = NOVA University Lisbon
26 Commenius University in Bratislava - Univerzita Komenského
27 EAS - European Atherosclerosis Society [Göteborg, Sweden]
28 University of Calgary
29 Henry Ford Hospital
30 CATAS - Chinese Academy of Tropical Agricultural Sciences
31 Middlemore Hospital
32 St. Vincent's Hospital, Sydney
33 MSU - Lomonosov Moscow State University = Université d'État Lomonossov de Moscou [Moscou]
34 Saitama Citizens Medical Center
35 Montreal Heart Institute - Institut de Cardiologie de Montréal
36 UdeM - Université de Montréal
37 NSC/MDSIC - National Scientific Center "M.D. Strazhesko Institute of Cardiology" [Kyiv, Ukraine]
38 Wrocław Medical University
39 USP - Universidade de São Paulo = University of São Paulo
40 Vilnius University [Vilnius]
41 University of Cape Town
42 MUNI - Masaryk University [Brno]
43 Inselspital - Bern University Hospital [Berne]
44 Saint John of God Clinical Research Centre
45 AZ Sint-Lucas
46 UMPCD - University of Medicine and Pharmacy “Carol Davila”
47 University of Groningen [Groningen]
48 DEÜ - Dokuz Eylül Üniversitesi = Dokuz Eylül University [Izmir]
49 DCAC - Défaillance Cardiovasculaire Aiguë et Chronique
50 CIC-P - Centre d'investigation clinique plurithématique Pierre Drouin [Nancy]
51 INI-CRCT - Cardiovascular and Renal Clinical Trialists [Vandoeuvre-les-Nancy]
52 Cardiovascular & Renal Clinical Trialists - CRCT - French-Clinical Research Infrastructure Network - F-CRIN [Paris]
53 AMGen - Applied Molecular Genetics
54 Laboratoire Servier
55 CI - Cytokinetics Inc
John R Teerlink
- Fonction : Auteur
- PersonId : 800306
- ORCID : 0000-0001-9527-0852
John J.V. Mcmurray
- Fonction : Auteur
- PersonId : 1093211
- ORCID : 0000-0002-6317-3975
John G.F. Cleland
- Fonction : Auteur
Résumé
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.).
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