Low-dose prasugrel-based antiplatelet therapy in patients with coronary artery disease

Potent P2Y12 inhibition with prasugrel has become central to the management of acute coronary syndrome in patients undergoing percutaneous coronary intervention. Early large-scale randomized trials established standard-dose prasugrel-based 12-month dual antiplatelet therapy (DAPT) as an effective strategy for reducing ischemic events compared with clopidogrel, albeit at the cost of increased bleeding risk. Over the past two decades, accumulating pharmacokinetic, pharmacodynamic, and clinical evidence has reshaped the therapeutic landscape. Studies have demonstrated that older adults, patients with low body weight, and East Asian populations exhibit greater platelet inhibition and higher exposure to the active metabolite at lower prasugrel doses. These biological differences provide a rationale for reduced maintenance dosing strategies. Concurrently, advances in stent technology and improved understanding of temporal risk patterns have supported progressive shortening of DAPT duration. Contemporary studies have evaluated abbreviated DAPT followed by prasugrel monotherapy, as well as aspirin-withdrawal strategies aimed at minimizing bleeding without compromising ischemic protection. Although very early aspirin-free approaches have yielded mixed results, selected short DAPT strategies followed by reduced-dose prasugrel have demonstrated favorable net clinical outcomes. Taken together, the evolution of prasugrel-based therapy reflects a paradigm shift from uniform high-intensity treatment toward individualized modulation of antiplatelet intensity. Low-dose prasugrel should be regarded not as a therapeutic compromise, but as a calibrated strategy designed to optimize the balance between ischemic protection and bleeding risk.