TY - JOUR
T1 - Cardiac myosin activation with omecamtiv mecarbil in systolic heart failure
AU - for the GALACTIC-HF Investigators
AU - Teerlink, John R.
AU - Díaz, Rafael
AU - Felker, G. Michael
AU - McMurray, John J.V.
AU - Metra, Marco
AU - Solomon, Scott D.
AU - Adams, Kirkwood F.
AU - Anand, Inder
AU - Arias-Mendoza, Alexandra
AU - Biering-Sorensen, Tor
AU - Böhm, Michael
AU - Bonderman, Diana
AU - Cleland, John G.F.
AU - Corbalan, Ramon
AU - Crespo-Leiro, Maria G.
AU - Dahlström, Ulf
AU - Echeverria, Luis E.
AU - Fang, James C.
AU - Filippatos, Gerasimos
AU - Fonseca, Candida
AU - Goncalvesova, Eva
AU - Goudev, Assen R.
AU - Howlett, Jonathan G.
AU - Lanfear, David E.
AU - Li, Jing
AU - Lund, Mayanna
AU - MacDonald, Peter
AU - Mareev, Viacheslav
AU - Momomura, Shin Ichi
AU - O'Meara, Eileen
AU - Parkhomenko, Alexander
AU - Ponikowski, Piotr
AU - Ramires, Felix J.A.
AU - Serpytis, Pranas
AU - Sliwa, Karen
AU - Spinar, Jindrich
AU - Suter, Thomas M.
AU - Tomcsanyi, Janos
AU - Vandekerckhove, Hans
AU - Vinereanu, Dragos
AU - Voors, Adriaan A.
AU - Yilmaz, Mehmet B.
AU - Zannad, Faiez
AU - Sharpsten, Lucie
AU - Legg, Jason C.
AU - Varin, Claire
AU - Honarpour, Narimon
AU - Coletti, Andrew
AU - Mignone, John
AU - Miyamoto, Michael
N1 - Publisher Copyright:
Copyright © 2020 Massachusetts Medical Society.
PY - 2021/1/14
Y1 - 2021/1/14
N2 - 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.).
AB - 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.).
UR - http://www.scopus.com/inward/record.url?scp=85099772364&partnerID=8YFLogxK
U2 - 10.1056/NEJMoa2025797
DO - 10.1056/NEJMoa2025797
M3 - Article
C2 - 33185990
AN - SCOPUS:85099772364
SN - 0028-4793
VL - 384
SP - 105
EP - 116
JO - New England Journal of Medicine
JF - New England Journal of Medicine
IS - 2
ER -