Low-dose rivaroxaban failed to improve outcomes in patients with worsening heart failure, reduced ejection fraction, and underlying coronary disease without atrial fibrillation in the COMMANDER HF trial.
The trial involved over 5,000 patients from 628 sites across 28 countries who were randomly assigned to rivaroxaban 2.5 mg, taken orally twice daily, or matching placebo in addition to guideline endorsed standard care.
During a median follow-up of 21.1 months, the primary efficacy outcome of all-cause mortality, myocardial infarction, or stroke occurred in 626 (25.0%) of 2,507 patients assigned to rivaroxaban compared to 658 (26.2%) of 2,515 on placebo (hazard ratio [HR] 0.94, 95% confidence interval [CI] 0.84–1.05, p=0.27).
There were no differences between groups in all-cause mortality (HR 0.98, 95% CI 0.87–1.10, p=0.74) or nonfatal myocardial infarction (HR 0.83, 95% CI 0.63–1.08, p=0.17) but there was a significantly lower rate of nonfatal stroke in the rivaroxaban, compared to placebo, group (HR 0.66, 95% CI 0.47–0.95, p=0.023).
The principal safety outcome of fatal bleeding or bleeding into a critical space occurred in 18 (0.7%) patients assigned to rivaroxaban and 23 (0.9%) assigned to placebo (HR 0.80, 95% CI 0.43–1.49, p=0.48).
Serious adverse events were reported in 479 (19.2%) patients taking rivaroxaban and 451 (18.0%) on placebo. The percentage of patients who permanently discontinued study medication due to an adverse event was 7.1% in the rivaroxaban group and 5.8% in the placebo group.
Professor Faiez Zannad, study author, University of Lorraine, Nancy, France, and colleagues said: “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.
“Indeed, readmission to the hospital for heart failure was the single most frequent event in the trial, and it is likely that heart failure, rather than deaths mediated by atherothrombotic events contributed to a substantial proportion of all deaths”.
Whether a higher dose of rivaroxaban could have led to a more favourable result is unknown.”
The study, published in the NEJM, was supported by Janssen Research and Development.