Balancing the benefits and risks of antiplatelet agents in patients with non-ST-segment elevated acute coronary syndromes and undergoing percutaneous coronary intervention.

Selecting appropriate antiplatelet therapy requires close attention to the delicate balance between reducing risk of ischemic events while minimizing bleeding risk. The broad range of available agents, while permitting tailoring of pharmacotherapy to individual patients, also complicates selection of optimal regimens. Platelet physiology provides an underpinning for the rationale behind pharmacotherapeutic strategies for patients with non-ST-segment elevated acute coronary syndromes (NSTE ACS) undergoing percutaneous coronary intervention (PCI). The same mechanisms of action that confer anti-ischemic benefit with antiplatelet agents may also be associated with increased risk. In the context of ACS and PCI, antiplatelet agents are used in complex strategies and combinations with other pharmacotherapies targeted at alleviating ischemic symptoms and reducing ischemic risk. Accounting for individual patient risk factors, timing of treatment, and dosage of antiplatelet medications minimizes risk while optimizing outcomes. This review examines results from clinical trials of thienopyridines (clopidogrel, ticlopidine, and the newer prasugrel), the new P2Y(12) antagonists ticagrelor and cangrelor, glycoprotein IIb-IIIa inhibitors (abciximab, eptifibatide, tirofiban), and the direct thrombin inhibitor bivalirudin. Recommendations include clopidogrel for use upstream if discontinued 5 days before coronary angiographic bypass graft. Bivalirudin remains a reasonable treatment choice in patients at low to moderate risk; and glycoprotein IIb-IIIa inhibitors confer anti-ischemic benefit with little incremental bleeding risk when individual patient factors are taken into account for their dosing. Increased awareness of the factors contributing to risks and benefits associated with the available antiplatelet agents will help guide physicians in choosing optimal regimens for all patients.