Rivaroxaban Plus Aspirin for Venous Thromboembolism Prevention

Quick Takes

  • Dual pathway inhibition includes the use of rivaroxaban 2.5 mg twice daily and low-dose aspirin for patients with significant atherosclerosis.
  • Data from the COMPASS trial confirm a reduction in incident VTE with dual pathway inhibition as compared to aspirin monotherapy.
  • Dual pathway inhibition was found to reduce VTE risk similarly in both the COMPASS and VOYAGER PAD trials.

Study Questions:

How effective is the dual pathway combination of rivaroxaban plus aspirin for preventing venous thromboembolism (VTE)?


In the original COMPASS (Cardiovascular Outcomes for People Using Anticoagulation Strategies) trial, patients with atherosclerotic coronary, carotid, or peripheral artery disease were randomized to receive dual pathway inhibition (rivaroxaban 2.5 mg twice daily plus aspirin 100 mg daily), rivaroxaban 5 mg twice daily, or aspirin 100 mg daily. The authors used stratified Cox proportional hazards regression to estimate the hazard ratios for developing VTE in the three treatment arms.


Of the 27,395 patients randomized to the three treatments, 102 experienced a VTE event. Patients randomized to dual pathway inhibition had a lower risk of VTE than patients randomized to aspirin monotherapy (0.3% vs. 0.4; hazard ratio [HR], 0.61; 95% confidence interval [CI], 0.37-1.00). Rivaroxaban monotherapy did not reduce VTE events as compared to aspirin monotherapy (0.4% vs. 0.4%; HR, 0.88; 95% CI, 0.56-1.38).


The authors concluded that dual pathway inhibition (rivaroxaban 2.5 mg twice daily plus aspirin 100 mg daily) reduced the risk of incident VTE as compared to aspirin monotherapy.


The COMPASS trial established the efficacy of dual pathway inhibition for patients with significant atherosclerotic disease. As was confirmed in the VOYAGER PAD trial, this treatment paradigm is particularly helpful for patients with peripheral artery disease, both in the post-procedure period and in the chronic phase. However, many patients with atherosclerosis are also at risk for VTE, perhaps due to shared risk factors (e.g., obesity, chronic kidney disease). These data from the COMPASS trial provide reassurance that when combined with low-dose aspirin, very low-dose rivaroxaban (2.5 mg twice daily) can provide some protection against incident VTE. Similar results were seen in a post hoc analysis of the VOYAGER study, where patients receiving dual pathway inhibition had an approximately 40% reduction in VTE risk compared to aspirin monotherapy. While not adequate for VTE secondary prevention in most patients at moderate to high risk of VTE recurrence, use of dual pathway inhibition can provide both arterial and venous thromboembolic protection in select individuals with a high burden of atherosclerosis.

Clinical Topics: Anticoagulation Management, Prevention, Pulmonary Hypertension and Venous Thromboembolism, Vascular Medicine, Atherosclerotic Disease (CAD/PAD), Anticoagulation Management and Venothromboembolism

Keywords: Anticoagulants, Aspirin, Atherosclerosis, Carotid Artery Diseases, Coronary Artery Disease, Obesity, Peripheral Arterial Disease, Primary Prevention, Renal Insufficiency, Chronic, Risk Factors, Rivaroxaban, Secondary Prevention, Vascular Diseases, Venous Thromboembolism

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