Physicians' Academy for Cardiovascular Education

Combination of DOAC with aspirin effective for prevention of stroke in patients with CAD or PAD

Stroke Outcomes in the Cardiovascular OutcoMes for People using Anticoagulation StrategieS (COMPASS) Trial

Literature - Sharma M, Hart RG, Connolly SJ et al. - Circulation 2019; Online published ahead of print

Introduction and methods

Although treatment with aspirin is recommended for CV prevention in individuals with atherosclerosis, aspirin reduces risk for major vascular events (myocardial infarction, stroke, or vascular death) by only 12% in primary prevention and 19% in secondary prevention [1]. A more effective antithrombotic strategy is therefore needed for prevention of major vascular events in patients with atherosclerosis. The Cardiovascular OutcoMes for People using Anticoagulation StrategieS (COMPASS) trial (n=27.395) therefore investigated the effect of rivaroxaban and aspirin vs. aspirin alone or rivaroxaban alone on stroke for prevention of vascular events in patients with stable coronary artery (CAD) or peripheral artery disease (PAD). This subanalysis investigated the effect on different stroke types, independent predictors of stroke, and effects in different key subgroups.

COMPASS was a double-blind, double-dummy trial including patients with stable CAD or PAD (including asymptomatic carotid artery stenosis ≥50% or previous carotid revascularization) who were randomized 1:1:1 to receive low-dose rivaroxaban (2.5 mg) twice daily plus aspirin 100 mg once daily (n=9.152), rivaroxaban 5 mg twice daily (n=9.117), or aspirin 100 mg once daily (n=9.126) for prevention of CV death, myocardial infarction, or stroke. The mean follow-up was 23 months.

Outcome was stroke, defined as the presence of acute focal neurological deficit thought to be of vascular origin with signs and symptoms lasting ≥24 hours or to time of death. Strokes were classified as: ischemic stroke, hemorrhagic stroke, or uncertain type of stroke. Abilities were evaluated by the modified Rankin Scale (mRS) and Standard Assessment of Global activities in the Elderly (SAGE) assessment.

Main results

Treatment effects on stroke incidence and severity

Baseline predictors of stroke and treatment effect in subgroups

Treatment effects in secondary prevention of stroke

Treatment effects in prevention of first stroke in high-risk patients


This subanalysis of the COMPASS trial showed that combination therapy with low-dose rivaroxaban plus aspirin reduced stroke in general and the subtype ischemic/uncertain stroke in patients with CAD or PAD without increased risk for hemorrhagic stroke. Treatment effects were similar across different key subgroups and prior stroke was the strongest predictor of stroke. This combination therapy is an important new option for efficacious antithrombotic therapy for primary and especially secondary prevention of stroke in patients with CAD or PAD.


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Find this article online at Circulation

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