Cardiac Myosin Activation with Omecamtiv Mecarbil in Systolic Heart Failure.

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.).

• Authors: John R Teerlink, Rafael Diaz, G Michael Felker, John J V McMurray, Marco Metra, Scott D Solomon, Kirkwood F Adams, Inder Anand, Alexandra Arias-Mendoza, Tor Biering-Sørensen, Michael Böhm, Diana Bonderman, John G F Cleland, 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, 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, GALACTIC-HF Investigators
• Journal: The New England journal of medicine (N Engl J Med) Vol. 384 Issue 2 Pg. 105-116 (01 14 2021) ISSN: 1533-4406 [Electronic] United States
• PMID: 33185990 (Publication Type: Clinical Trial, Phase III, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2020 Massachusetts Medical Society.

Chemical References

• Cardiotonic Agents
• omecamtiv mecarbil
• Urea
• Cardiac Myosins

Topics

• Aged
• Aged, 80 and over
• Cardiac Myosins (drug effects, metabolism)
• Cardiotonic Agents (adverse effects, pharmacology, therapeutic use)
• Cardiovascular Diseases (mortality)
• Female
• Heart Failure, Systolic (drug therapy, metabolism, physiopathology)
• Humans
• Male
• Middle Aged
• Myocardial Contraction (drug effects)
• Stroke Volume
• Urea (adverse effects, analogs & derivatives, pharmacology, therapeutic use)