Cardiac myosin activation with omecamtiv mecarbil in systolic heart failure

Teerlink, J. R. et al. (2020) Cardiac myosin activation with omecamtiv mecarbil in systolic heart failure. New England Journal of Medicine, (doi: 10.1056/NEJMoa2025797) (Early Online Publication)

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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. opens in new tab; EudraCT number, 2016-002299-28. opens in new tab.)

Item Type:Articles
Status:Early Online Publication
Refereed:Yes
Glasgow Author(s) Enlighten ID:Cleland, Professor John and McMurray, Professor John
Authors: Teerlink, J. R., Diaz, R., Felker, G. M., McMurray, J. J.V., Metra, M., Solomon, S. D., Adams, K. F., Anand, I., Arias-Mendoza, A., Biering-Sørensen, T., Böhm, M., Bonderman, D., Cleland, J. G.F., Corbalan, R., Crespo-Leiro, M. G., Dahlström, U., Echeverria, L. E., Fang, J. C., Filippatos, G., Fonseca, C., Goncalvesova, E., Goudev, A. R., Howlett, J. G., Lanfear, D. E., Li, J., Lund, M., Macdonald, P., Mareev, V., Momomura, S.-i., O’Meara, E., Parkhomenko, A., Ponikowski, P., Ramires, F. J.A., Serpytis, P., Sliwa, K., Spinar, J., Suter, T. M., Tomcsanyi, J., Vandekerckhove, H., Vinereanu, D., Voors, A. A., Yilmaz, M. B., Zannad, F., Sharpsten, L., Legg, J. C., Varin, C., Honarpour, N., Abbasi, S. A., Malik, F. I., and Kurtz, C. E.
Subjects:R Medicine > R Medicine (General)
College/School:College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
College of Medical Veterinary and Life Sciences > Institute of Health and Wellbeing > Robertson Centre
Journal Name:New England Journal of Medicine
ISSN:0028-4793
ISSN (Online):1533-4406
Published Online:13 November 2020
Copyright Holders:Copyright © 2020 Massachusetts Medical Society
First Published:First published in New England Journal of Medicine 2020
Publisher Policy:Reproduced in accordance with the publisher copyright policy

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