Rivaroxaban in patients with heart failure, sinus rhythm, and coronary disease

Zannad, F. et al. (2018) Rivaroxaban in patients with heart failure, sinus rhythm, and coronary disease. New England Journal of Medicine, 379, pp. 1332-1342. (doi: 10.1056/NEJMoa1808848) (PMID:30146935)

Abstract

Background: Heart failure is associated with activation of thrombin-related pathways, which predicts a poor prognosis. We hypothesized that treatment with rivaroxaban, a factor Xa inhibitor, could reduce thrombin generation and improve outcomes for patients with worsening chronic heart failure and underlying coronary artery disease. Methods: In this double-blind, randomized trial, 5022 patients who had chronic heart failure, a left ventricular ejection fraction of 40% or less, coronary artery disease, and elevated plasma concentrations of natriuretic peptides and who did not have atrial fibrillation were randomly assigned to receive rivaroxaban at a dose of 2.5 mg twice daily or placebo in addition to standard care after treatment for an episode of worsening heart failure. The primary efficacy outcome was the composite of death from any cause, myocardial infarction, or stroke. The principal safety outcome was fatal bleeding or bleeding into a critical space with a potential for causing permanent disability. Results: Over a median follow-up period of 21.1 months, the primary end point occurred in 626 (25.0%) of 2507 patients assigned to rivaroxaban and in 658 (26.2%) of 2515 patients assigned to placebo (hazard ratio, 0.94; 95% confidence interval [CI], 0.84 to 1.05; P=0.27). No significant difference in all-cause mortality was noted between the rivaroxaban group and the placebo group (21.8% and 22.1%, respectively; hazard ratio, 0.98; 95% CI, 0.87 to 1.10). The principal safety outcome occurred in 18 patients who took rivaroxaban and in 23 who took placebo (hazard ratio, 0.80; 95% CI, 0.43 to 1.49; P=0.48). Conclusions: Rivaroxaban at a dose of 2.5 mg twice daily was not associated with a significantly lower rate of death, myocardial infarction, or stroke than placebo among patients with worsening chronic heart failure, reduced left ventricular ejection fraction, coronary artery disease, and no atrial fibrillation. (Funded by Janssen Research and Development; COMMANDER HF ClinicalTrials.gov number, NCT01877915.)

• Item Type: Articles
• Additional Information: Supported by Janssen Research and Development.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Cleland, Professor John
• Authors: Zannad, F., Anker, S. D., Byra, W. M., Cleland, J. G.F., Fu, M., Gheorghiade, M., Lam, C. S.P., Mehra, M. R., Neaton, J. D., Nessel, C. C., Spiro, T. E., van Veldhuisen, D. J., and Greenberg, B.
• Subjects: R Medicine > R Medicine (General)
• College/School: College of Medical Veterinary and Life Sciences > School of Health & Wellbeing > Robertson Centre
• Journal Name: New England Journal of Medicine
• Publisher: Massachusetts Medical Society
• ISSN: 0028-4793
• ISSN (Online): 1533-4406
• Published Online: 27 August 2018
• Copyright Holders: Copyright © 2018 Massachusetts Medical Society
• First Published: First published in New England Journal of Medicine 379:1332-1342
• Publisher Policy: Reproduced in accordance with the publisher copyright policy