MUNICH – For patients with heart disease, coronary artery disease, and normal sinus rhythm, giving , investigators in the COMMANDER trial said.
Rivaroxaban did not improve rehospitalization rates either, reported lead author Faiez Zannad, MD, PhD, from the University of Henri Poincaré in Nancy, France, and his co-investigators.
“After an episode of worsening chronic heart failure, rates of readmission to the hospital and of death are high, especially in the first few months,” they said in a presentation at the annual congress of the European Society of Cardiology. The report of the research was published simultaneously in the New England Journal of Medicine.
Findings from previous research have suggested that, for patients with coronary artery disease, a combination of antiplatelet agents and low-dose rivaroxaban (2.5 mg twice daily) reduced incidence of death, myocardial infarction, and stroke. The authors designed the COMMANDER trial to test a similar regimen in patients with chronic heart failure and coronary heart disease without an arrhythmia. Results were published simultaneously in the New England Journal of Medicine.
The COMMANDER trial involved 5,022 patients with coronary artery disease, reduced left ventricular ejection fraction (less than or equal to 40%), worsening chronic heart failure (index event within past 21 days), and normal splasma concentration of brain natriuretic peptide (BNP) of at least 200 ng per liter or N-terminal pro-brain natriuretic peptide (NT-proBNP) of at least 800 ng per liter.
Patients were randomly assigned to receive rivaroxaban 2.5 mg twice daily (n = 2,507) or placebo (n = 2,515). Treatment was given in addition to standard care for coronary disease or heart failure (single or dual antiplatelet therapy was allowed). Patients were assessed at week 4 and week 12, then every 12 weeks.
The primary efficacy outcome was a composite of stroke, myocardial infarction, or death from any cause. Secondary efficacy outcomes included death from cardiovascular disease, rehospitalization for heart failure, a composite of either, or rehospitalization for cardiovascular events. The principal safety outcome was a composite of bleeding into a critical space with potential for permanent disability or fatal bleeding.
Death, myocardial failure, or stroke occurred in 626 patients (25%) in the rivaroxaban group compared with 658 patients (26.2%) in the placebo group (P = .27). Secondary efficacy outcomes were also highly similar between groups, differing at most by 0.9%. The principal safety outcome (fatal bleeding or bleeding into a critical space) occurred in 18 patients (0.7%) in the rivaroxaban group and 23 patients (0.9%) in the placebo group (P = .25). Again, no significant difference was found between groups.
These results suggest that while low-dose rivaroxaban may be safe, it also offers no treatment benefit. “The most likely reason for the failure … is that thrombin-mediated events are not the major driver of heart failure-related events in patients with recent hospitalization for heart failure,” the authors wrote.
“Whether a higher dose of rivaroxaban could have led to a more favorable outcome remains unknown,” they concluded.
The COMMANDER trial was funded by Janssen Research and Development. Authors reported compensation from Bayer, Servier, Novartis, Impulse Dynamics, and others.