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