Balancing Benefits and Risks of Oral Antiplatelet Strategies in patients With Coronary Artery Diseases: An Evolving Issue

Identifying the most appropriate antiplatelet therapy for each patient to prevent ischemic events while minimizing the risk of bleeding is an integral part of the short- and long-term management of patients with coronary artery disease (CAD). This review aims to summarize the available evidence on the contemporary use of P2Y12 inhibitors in CAD patients, focusing on strategies aimed at providing adequate ischemic protection while preventing bleeding risk through dual antiplatelet therapy (DAPT) modulation. Randomized trials and observational studies have been reviewed to determine the most appropriate antiplatelet treatment for CAD patients with different risk profiles. Both ischemic and bleeding events have a significant prognostic impact and should be carefully considered in clinical decision-making. Current guidelines recommend the use of third-generation PY2Y12 inhibitors (prasugrel or ticagrelor) over clopidogrel, as a part of DAPT, in patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention. Newer P2Y12 inhibitors have a more rapid onset of action and less interindividual variability in platelet inhibition than clopidogrel but are associated with an increased risk of bleeding that may limit their benefit. Importantly, the anti-ischemic benefit of ticagrelor and prasugrel is mainly observed in the first weeks after ACS, whereas clopidogrel seems to provide the best balance between ischemic protection and bleeding as long-term maintenance therapy. These concepts support DAPT modulation after the acute phase, by de-escalating from full-dose to low-dose newer P2Y12 inhibitors, by switching to clopidogrel, or by early withdrawing aspirin to maximize both the efficacy and safety of antiplatelet therapy in patients with CAD.