In the COMPASS trial, the combination of rivaroxaban 2.5 mg twice daily and low-dose aspirin 75–100 mg daily produced a net clinical benefit of 20% in patients with chronic atherosclerotic vascular disease because it reduced major adverse events by 24% and overall mortality by 18% despite an initial increase in major bleeding. In this paper, we examine the rationale for targeting coagulation factor Xa in patients with atherosclerosis, summarize the pharmacology of the 2.5-mg dose, review the trials that led to the approval of the combination of rivaroxaban and aspirin for the long-term management of patients with chronic coronary artery disease or peripheral artery disease and discuss who would benefit the most. We also address the unresolved issues and challenges in the implementation of this therapy.
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