Outcomes With Rivaroxaban in Chronic Heart Failure With Underlying CAD

Rivaroxaban was not superior to placebo for reducing the rate of death, MI, or stroke in patients with chronic heart failure.

In patients with reduced left ventricular ejection fraction (LVEF), coronary artery disease, and worsening chronic heart failure, twice-daily rivaroxaban, 2.5 mg, was not superior to placebo for reducing the rate of death, myocardial infarction, or stroke in a study presented at the European Society of Cardiology Congress in Munich, Germany, and simultaneously published in the New England Journal of Medicine.

Patients without atrial fibrillation but with at least a 3-month history of either chronic heart failure, reduced LVEF (≤40%), coronary artery disease, and increased plasma concentrations of natriuretic peptides were enrolled in the COMMANDER-HF trial (ClinicalTrials.gov Identifier: NCT01877915). Study investigators randomly assigned patients to either rivaroxaban, 2.5 mg twice daily (n=2507), or placebo (n=2515) plus standard care following treatment for worsening heart failure. A composite of death from any cause, myocardial infarction, or stroke comprised the primary efficacy outcome, whereas the principal safety outcomes included fatal bleeding or bleeding associated with a risk of permanent disability.

During a median 21.1-month follow-up, the primary end point was observed in 25.0% (n=626) and 26.2% (n=658) of patients randomly assigned to rivaroxaban and placebo, respectively (hazard ratio [HR] 0.94; 95% CI, 0.84-1.05; P =.27). With regard to the rates of all-cause mortality, there were no differences between the rivaroxaban and placebo groups (21.8% and 22.1%, respectively; HR 0.98; 95% CI, 0.87-1.10). Additionally, there was no difference between rivaroxaban and placebo with regard to the number of patients who met the principal safety outcome during treatment (HR 0.80; 95% CI, 0.43-1.49; P =.48).

The lack of adjudication of events represents a limitation that likely reduced the researchers’ ability to determine the exact causes of hospitalizations and death.

“The most likely reason for the failure of rivaroxaban at a dose of 2.5 mg twice daily to improve cardiovascular outcomes in the current trial is that thrombin-mediated events are not the major driver of heart failure-related events in patients with recent hospitalization for heart failure,” the investigators wrote.

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Disclosures: This study was supported by Janssen Research and Development.

Reference

Zannad F, Anker SD, Byra WM, et al; for the COMMANDER HF Investigators. Rivaroxaban in patients with heart failure, sinus rhythm, and coronary disease [published online August 27, 2018]. N Engl J Med. doi:10.1056/NEJMoa1808848