Rivaroxaban With or Without Aspirin for the Secondary Prevention of Cardiovascular Disease

Clinical Implications of the COMPASS Trial

Stephen J. Nicholls; Adam J. Nelson


Am J Cardiovasc Drugs. 2019;19(4):343-348. 

In This Article

Abstract and Introduction


The COMPASS trial compared the impact of the selective direct factor Xa inhibitor, rivaroxaban, as monotherapy or in combination with aspirin on major adverse cardiovascular events (MACE) in patients with stable atherosclerotic disease. Patients treated with rivaroxaban 2.5 mg twice daily in combination with aspirin experienced fewer cardiovascular events but more bleeding complications than those who received aspirin monotherapy. In contrast, a higher dose of rivaroxaban (5 mg twice daily) and aspirin produced no clinical benefit and continued to be associated with greater bleeding rates than aspirin. Examining this study in the context of other trials of anticoagulant therapy in atherosclerotic vascular disease, this review attempts to place the role of very low-dose rivaroxaban in clinical context and highlights areas for future research.


Increasing evidence has unequivocally demonstrated the benefits of a range of antiplatelet agents as secondary prevention in atherosclerotic cardiovascular disease.[1–3] More recent studies have attempted to define the optimal use of these agents, with a particular focus on the duration of combination therapy and its relative effects on both efficacy and safety.[4–6] Parallel studies have also attempted to determine the clinical effects of oral anticoagulants in combination with antiplatelet therapy[7–10] in the context of patients with indications for both. This is commonly encountered in the setting of atrial fibrillation (AF), where up to one-third of patients have comorbid coronary artery disease.[11]

The theoretical benefits of using anticoagulant therapy in patients with atherosclerotic cardiovascular disease reflect the complex orchestra of events involved in the generation of arterial thrombosis. Insights from pathology studies have demonstrated that exposure of plaque contents to circulating blood, as a result of either rupture or erosion events, stimulates activation of both platelets and the coagulation cascade, leading to clot formation.[12,13] Accordingly, therapeutic targeting with both antiplatelet and anticoagulant therapy has the potential to treat both of these factors more extensively than antiplatelet agents alone.