COMPASS Trial Afterthoughts

The direct oral anticoagulants (DOACS) have been finding extended utility since their discovery. Their progress in the realm of coronary disease (CAD), however, has been inconsistent. In APPRAISE 2, higher-dose (5 mg) anticoagulation with apixaban was not beneficial after acute coronary syndrome (ACS), and in fact, was associated with excessive bleeding. In the ATLAS ACS 2 study, rivaroxaban, at doses of 2.5 and 5 mg twice a day, when added to a regimen of dual antiplatelet therapy after ACS reduced vascular events and mortality.

Results of theCOMPASS (Cardiovascular Outcomes for People Using Anticoagulation Strategies) trial are a positive addition to the DOAC-CAD data.

Patients with stable CAD-most many years away from either an ACS or revascularization procedure-given rivaroxaban, 2.5 mg twice a day in combination with 100 mg daily aspirin-experienced a 26% reduction in major vascular events and a 24% decrease in death. So, COMPASS has expanded the ATLAS ACS 2 results by demonstrating that the addition of rivaroxaban to aspirin therapy is beneficial.

The authors were transparent about the downsides of the rivaroxaban-aspirin regimen. First of all, 5 mg twice daily of rivaroxaban had been tried, but caused excessive bleeding. The 2.5 mg twice daily rivaroxaban-aspirin regimen led to major bleeding in 263/8313 patients or 3% compared to 2% (158/8261) in the aspirin alone group. The most common site of bleeding in the rivaroxaban/aspirin cohort was gastrointestinal. However, intracranial and fatal bleeding were not significantly different between aspirin alone versus aspirin +  rivaroxaban. Patients of advanced age experienced more bleeding events. Also, the design of the study led to more patients ingesting a proton pump inhibitor than in usual practice.

Does the beneficial vascular and overall mortality advantage seen with the aspirin/rivaroxaban combinatinon trump the observed major bleeding risk? Which combinatinon/s are most effective in your practice?

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