The New England journal of medicine 2018-10-04
Rivaroxaban in Patients with Heart Failure, Sinus Rhythm, and Coronary Disease.
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 .).
Related Questions
Would you consider anticoagulation for a young patient with a recent embolic stroke and newly diagnosed global cardiac hypokinesis with ejection fraction of less than 25%?
Yes, I would consider anticoagulation but the evidence is indirect. There is reasonable data in persons with heart failure with reduced ejection fraction that ischemic stroke is reduced with anticoagulation compared to antiplatelet therapy alone. But essentially all large RCTs are limited in that th...
When do you start anticoagulation for secondary prevention in patients with HFrEF and history of embolic strokes?
Current guidelines consider anticoagulation in patients with reduced EF as class III (no benefit and possibility of harm), which has not changed significantly since WARCEF was published. The most recent randomized large trial, COMMANDER HF, looked at primary stroke prevention (among other thrombotic...