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Dual antiplatelet therapy with aspirin and the oral P2Y
inhibitor clopidogrel as the cornerstone of treatment for patients with an acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI) was firstly established in 2001. Soon thereafter, the newer-generation P2Y
inhibitors prasugrel and ticagrelor became commercially available. The clinical management of ACS patients undergoing PCI has evolved significantly in the last 2 decades, with a shift toward more rapid invasive management, broader use of drug-eluting stents, and the increasing recognition that major bleeding due to antiplatelet therapy is detrimental. In this ever-changing scenario, numerous studies have addressed 4 main questions regarding P2Y
inhibition in ACS patients undergoing PCI: timing, selection, modulation, and duration. This paper reviews the latest evidence surrounding these topical questions, with a focus on efficacy and safety data, practice guidelines, and residual areas of uncertainty.