Low-dose rivaroxaban in addition to guideline-based therapy did not reduce the composite outcome of death from any cause, myocardial infarction, or stroke compared with placebo in patients with underlying coronary artery disease and experiencing an episode of worsening heart failure. Researchers presenting on the findings from the COMMANDER HF Trial on Aug. 27 during ESC Congress 2018, also noted no significant difference in the rate of hospitalizations for heart failure.

The trial, also published in the New England Journal of Medicine, randomly assigned 5,022 patients from 628 sites in 28 countries to either rivaroxaban (2.5 mg/orally, twice daily) or matching placebo. Additionally, patients received guideline-recommended therapies for heart failure and coronary artery disease, including diuretics, angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, beta-blockers, and mineralocorticoid receptor antagonists. Nearly all patients were taking aspirin and a substantial number were also receiving dual antiplatelet agents at the time either rivaroxaban or placebo was initiated. The primary endpoint was all-cause mortality, myocardial infarction, or stroke, with the primary safety endpoint being the composite of fatal or major bleeding.

During a median follow-up of 21.1 months, the primary endpoint occurred in 25.0 percent (626) of 2,507 patients assigned to rivaroxaban compared with 26.2 percent (658) of the 2,515 on placebo. Researchers noted no differences between groups in all-cause mortality or nonfatal myocardial infarction. However, there was a significantly lower rate of nonfatal stroke in the rivaroxaban group, compared with the placebo group. The primary safety outcome occurred in 0.7 percent (18) of patients assigned to rivaroxaban and 0.9 percent (23) assigned to placebo. Patients taking rivaroxaban did have a significantly higher risk of major bleeding compared with those on placebo.

In other findings, serious adverse events were reported in 19.2 percent of patients taking rivaroxaban and 18.0 percent of patients taking placebo. The percentage of patients who permanently discontinued the study medication was higher in the rivaroxaban group (7.1 percent) than the placebo group (5.8 percent).

"The most likely reason rivaroxaban failed to improve the primary efficacy outcome is that thrombin-mediated events are not the major driver of cardiovascular events in patients with recent heart failure hospitalisation," said Professor Faiez Zannad, study author, University of Lorraine, Nancy, France. "Whether a higher dose of rivaroxaban could have led to a more favourable result is unknown."

Keywords: ESC18, ESC Congress, Coronary Artery Disease, Heart Failure

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