Five to 10% of patients with cardiovascular disease have recurrent events each year. Despite evidence in support of adding warfarin to antiplatelet agents for secondary prevention among at-risk patients, the countervailing bleeding risks have limited adoption in clinical practice. Given the potentially favorable risk profile of direct oral anticoagulants compared to warfarin, these agents have generated interest as potential adjunctive therapy for secondary cardiovascular prevention.

The Cardiovascular Outcomes for People Using Anticoagulation Strategies (COMPASS) trial randomized 27,395 patients with stable cardiovascular disease to receive either rivaroxaban 2.5 mg twice daily plus aspirin, rivaroxaban 5 mg twice daily alone, or aspirin alone in double blind fashion in addition to standard medical therapy.  The primary outcome was a composite of cardiovascular death, stroke or myocardial infarction.  The trial was stopped at 23 months due to superiority of rivaroxaban plus aspirin, which was associated with a significant decrease in the primary outcome (4.1 vs 5.4%, p<0.001) and an 0.7% absolute decrease in all-cause mortality (p = NS), though was also associated with more major bleeding (3.1 vs 1.9%, p<0.001) when compared to aspirin alone.  There was no significant difference in fatal bleeding or intracranial hemorrhage between these two groups. Compared to aspirin alone, rivaroxaban alone did not significantly decrease thrombotic events but resulted in increased major bleeding (2.8 vs 1.9%, p<0.001).

Conclusions

The COMPASS trial further solidifies the notion that there is no such thing as a free lunch when it comes to secondary prevention of thrombotic cardiovascular events.  Despite the positive results demonstrated here, it is unclear whether patients and providers will routinely tolerate increased bleeding rates for a reduction in thrombotic events that can not be immediately perceived on an individual basis. Rivaroxaban should be considered as an adjunct to aspirin for those at highest risk of recurrent events, though how this fits with dual antiplatelet therapy is unclear.

Eikelboom JW, Connolly SJ, Bosch J, et al. Rivaroxaban with or without aspirin in stable cardiovascular disease. N Engl J Med 2017;377:1319-30.

Shannon McConnaughey (UW Department of Medicine) and James M. McCabe (UW Division of Cardiology)