• Faiez Zannad, Stefan D Anker, William M Byra, Cleland John G F JGF From the Université de Lorraine, INSERM Unité 1116 and Clinical Investigation Center 1433, French Clinical Research Infrastructure Network, Investiga, Min Fu, Mihai Gheorghiade, Lam Carolyn S P CSP From the Université de Lorraine, INSERM Unité 1116 and Clinical Investigation Center 1433, French Clinical Research Infrastructure Network, Investigat, Mandeep R Mehra, James D Neaton, Christopher C Nessel, Theodore E Spiro, Dirk J van Veldhuisen, Barry Greenberg, and COMMANDER HF Investigators.
• From the Université de Lorraine, INSERM Unité 1116 and Clinical Investigation Center 1433, French Clinical Research Infrastructure Network, Investigation Network Initiative-Cardiovascular and Renal Clinical Trialists, Centre Hospitalier Régional et Universitaire de Nancy, Vandoeuvre lès Nancy, France (F.Z.); the Department of Cardiology and Berlin-Brandenburg Center for Regenerative Therapies, German Center for Cardiovascular Research partner site Berlin, Charité Universitätsmedizin Berlin, Berlin (S.D.A.); Janssen Research and Development, Raritan (W.M.B., C.C.N.), and Bayer U.S., Research and Development, Pharmaceuticals, Thrombosis and Hematology Therapeutic Area, Whippany (T.E.S.) - both in New Jersey; Robertson Centre for Biostatistics and Clinical Trials, University of Glasgow, Glasgow, and the National Heart and Lung Institute, Imperial College London, London - both in the United Kingdom (J.G.F.C.); Janssen Research and Development, Spring House, PA (M.F.); Northwestern University, Chicago (M.G.); National Heart Centre Singapore and Duke-National University of Singapore, Singapore (C.S.P.L.); the Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands (C.S.P.L., D.J.V.); Brigham and Women's Hospital and Harvard Medical School, Boston (M.R.M.); the Division of Biostatistics, School of Public Health, University of Minnesota, Minneapolis (J.D.N.); and the Department of Medicine, Cardiology Division, University of California, San Diego, San Diego (B.G.).
• N. Engl. J. Med. 2018 Oct 4; 379 (14): 1332-1342.

BackgroundHeart 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.MethodsIn 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.ResultsOver 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).ConclusionsRivaroxaban 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 .).

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