Small peptide GP IIb/IIIa receptor inhibitors as upstream therapy in non-ST-segment elevation acute coronary syndromes: results of the PURSUIT, PRISM, PRISM-PLUS, TACTICS, and PARAGON trials.

Abstract

The primary pathophysiologic mechanism underlying all non-ST-segment elevation acute coronary syndromes (NSTE ACS) is the formation of platelet-rich coronary thrombi in response to spontaneous or intervention-induced endothelial damage with exposure of subendothelial substrates. Antagonists of the glycoprotein (GP) IIb/IIIa receptor ameliorate this process by blocking the final common pathway for platelet aggregation. Based upon collective data in over 24,000 patients, clinical trials have demonstrated that treatment of NSTE ACS patients with GP IIb/IIIa agents results in an approximate 12% relative risk reduction in the incidence of death or myocardial infarction at 30 days. The magnitude of this clinical benefit is increased in patients who are troponin-positive and who are referred for early percutaneous intervention. Potential benefits of GP IIb/IIIa inhibitor use must be weighed against an increased risk of bleeding. Ongoing controversies exist concerning the relative efficacy of different GP IIb/IIIa antagonists, the accurate use of platelet function tests to define safe and efficacious drug dosing, the adjunctive use of additional anti-thrombotic agents, and the optimal timing of upstream therapy before diagnostic cardiac catheterization and revascularization.