Prasugrel: Reassessing Its Role in Contemporary Antiplatelet Therapy

Managing acute coronary syndrome (ACS) and atherosclerotic cardiovascular disease remains clinically challenging, requiring a careful balance between ischemic protection and bleeding risk. Antiplatelet therapy is central to the management, with aspirin serving as the cornerstone; however, selection of the second antiplatelet agent in dual antiplatelet therapy (DAPT) remains complex. Clopidogrel, a purinergic receptor subtype Y, G protein-coupled, 12 (P2Y₁₂) inhibitor, is widely used but is limited by substantial interindividual variability in antiplatelet response, particularly in populations with a high prevalence of CYP2C19 loss-of-function polymorphisms. These limitations prompted the development of more potent P2Y₁₂ inhibitors, including prasugrel and ticagrelor, which provide faster and more consistent platelet inhibition. However, clinical experience-especially in Asian populations-has highlighted that a "one-size-fits-all" dosing strategy may not be appropriate, as heightened bleeding risk can offset ischemic benefit. This review reexamines the contemporary role of prasugrel, focusing on evidence supporting dose optimization, careful patient selection, and population-specific considerations. Current evidence suggests that prasugrel remains a valuable antiplatelet option when tailored to individual ischemic and bleeding risks, particularly in patients undergoing complex percutaneous coronary intervention and selected Asian populations requiring individualized antiplatelet strategies.