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.