Dual Pathway Inhibition: Redefining the Secondary Prevention COMPASS in Chronic Coronary Artery Disease

Abstract Chronic coronary artery disease (CAD) remains a leading cause of morbidity and mortality worldwide, despite advances in pharmacological and interventional therapies. Aspirin has long been the cornerstone of secondary prevention; however, residual cardiovascular risk persists in many patients, especially those with additional high-risk features such as diabetes, polyvascular disease, or renal dysfunction. The concept of dual pathway inhibition (DPI) combining low-dose anticoagulation with antiplatelet therapy has emerged as a novel strategy to enhance vascular protection. The COMPASS trial provided pivotal evidence supporting the use of low-dose rivaroxaban (2.5 mg twice daily) in combination with aspirin (100 mg daily), demonstrating significant reductions in major adverse cardiovascular events without a corresponding increase in fatal or intracranial bleeding. While the COMPASS study enrolled patients with sinus rhythm (oral anticoagulation naive) and used a special dose of DAOC, the recently published AQAUTIC study looked at CAD with prior oral anticoagulation. There was no benefit of adding aspirin to standard dose anticoagulation, and hence, such patients are not candidates for DPI. This review explores the rationale behind DPI, key findings from the COMPASS trial in chronic CAD patients, and the implications for clinical practice. It also discusses patient selection strategies, drug interactions, safety considerations, and current guideline recommendations. A proposed clinical algorithm is presented to guide the practical application of DPI in appropriately selected patients with stable CAD, aiming to redefine secondary prevention and improve long-term cardiovascular outcomes.