Cardiovascular Disease and Rivaroxaban Study

Cardiovascular diseases are the leading cause of death globally. Though new medications and the use of effective secondary prevention strategies, 5% to 10% of patients with cardiovascular disease have recurrent events each year with worst outcomes mostly being cardiac death. Rivaroxaban is used to prevent blood clots from forming due to atrial fibrillation; however, it's known to cause a major risk of bleeding when given higher doses, hence its safety is a question mark for its regular use.

A new trial, COMPASS, by Dr. John W. Eikelboom, M.B.B.S. and team revealed that patients with stable atherosclerotic vascular disease, those assigned to rivaroxaban (2.5 mg twice daily) plus aspirin had better cardiovascular outcomes and more major bleeding events than those assigned to aspirin alone. 5 mg of rivaroxaban twice daily alone did not help any better than aspirin alone and resulted in more major bleeding events.

The trial is published in The New England Journal of Medicine.

Objective of the Trial

The objective of the trial was to evaluate whether rivaroxaban alone or in combination with aspirin would be more effective than aspirin alone for secondary cardiovascular event prevention.

Trial Design

The trial was a double-blinded trial, 27,395 participants with stable atherosclerotic vascular disease were randomly assigned to receive rivaroxaban (2.5 mg twice daily) plus aspirin (100 mg once daily), rivaroxaban (5 mg twice daily), or aspirin (100 mg once daily). The primary outcome was a composite of cardiovascular death, stroke, or myocardial infarction. The study was stopped for superiority of the rivaroxaban-plus-aspirin group after a mean follow-up of 23 months.

Results of the Trial

• The primary outcome occurred in fewer patients in the rivaroxaban-plus-aspirin group than in the aspirin-alone group (379 patients vs. 496 patients; HR 0.76; 0.66 to 0.86; P<0.001; z=−4.126).
• Major bleeding events occurred in more patients in the rivaroxaban-plus-aspirin group (288 patients vs. 170 patients; HR, 1.70; 1.40 to 2.05; P<0.001).
• There was no significant difference in intracranial or fatal bleeding between these two groups. There were 313 deaths in the rivaroxaban-plus-aspirin group as compared with 378 in the aspirin-alone group (HR, 0.82, 0.71 to 0.96; P=0.01; threshold P value, 0.0025).
• The primary outcome did not occur in significantly fewer patients in the rivaroxaban-alone group than in the aspirin-alone group, but major bleeding events occurred in more patients in the rivaroxaban-alone group.

Conclusion

Dr. John and team concluded that "Among patients with stable atherosclerotic vascular disease, those assigned to rivaroxaban (2.5 mg twice daily) plus aspirin had better cardiovascular outcomes and more major bleeding events than those assigned to aspirin alone. Rivaroxaban (5 mg twice daily) alone did not result in better cardiovascular outcomes than aspirin alone and resulted in more major bleeding events."

Reference: DOI: 10.1056/NEJMoa1709118