Aspirin or P2Y₁₂ inhibitor monotherapy in atherosclerotic cardiovascular disease?

Antiplatelet therapy is the cornerstone of treatment in patients with established atherosclerotic disease. The use of a single antiplatelet agent is commonly recommended for the long-term management of these patients. Although aspirin has represented the mainstay of antiplatelet therapy for decades, emerging evidence suggests that P2Y₁₂ inhibitors may be more than just a viable alternative to aspirin and may be preferred over aspirin. This review examines the current evidence comparing the efficacy and safety of aspirin vs P2Y₁₂ inhibitors in reducing cardiovascular events in patients with atherosclerotic disease. Special attention is given to the practical challenges and considerations surrounding the use of aspirin vs P2Y₁₂ inhibitor monotherapy, including interindividual variability in drug response, side effects, costs, and real-world implementation. By evaluating the strengths and limitations of these treatment options, this article aims to guide clinicians in optimizing the selection of single antiplatelet strategies for long-term secondary prevention in patients with atherosclerotic disease.