Rivaroxaban in Patients with Heart Failure, Sinus Rhythm, and Coronary Disease

N Engl J Med. 2018 Oct 4;379(14):1332-1342. doi: 10.1056/NEJMoa1808848. Epub 2018 Aug 27.

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 .).

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Coronary Artery Disease / complications
  • Coronary Artery Disease / drug therapy*
  • Double-Blind Method
  • Drug Therapy, Combination
  • Factor Xa Inhibitors / adverse effects
  • Factor Xa Inhibitors / therapeutic use*
  • Female
  • Follow-Up Studies
  • Heart Failure / complications
  • Heart Failure / drug therapy*
  • Heart Failure / mortality
  • Heart Failure / physiopathology
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Myocardial Infarction / epidemiology
  • Myocardial Infarction / prevention & control
  • Natriuretic Peptide, Brain / blood
  • Patient Readmission / statistics & numerical data
  • Platelet Aggregation Inhibitors / therapeutic use
  • Rivaroxaban / adverse effects
  • Rivaroxaban / therapeutic use*
  • Stroke / epidemiology
  • Stroke / prevention & control
  • Stroke Volume
  • Treatment Failure

Substances

  • Factor Xa Inhibitors
  • Platelet Aggregation Inhibitors
  • Natriuretic Peptide, Brain
  • Rivaroxaban

Associated data

  • ClinicalTrials.gov/NCT01877915