Current Role of Platelet Glycoprotein IIb/IIIa Inhibition in the Therapeutic Management of Acute Coronary Syndromes in the Stent Era

Abstract

The pathophysiology of acute coronary syndromes (ACS) is characterized by disruption of atherosclerotic plaques, activation and aggregation of platelets, and formation of an arterial thrombus. Thrombus formation can result in either transient or persistent occlusion giving rise to the spectrum of ACS. This syndrome defines rapidly evolving symptoms of myocardial ischemia ranging from unstable angina pectoris to non-Q-wave myocardial infarction to Q-wave myocardial infarction. An early pharmacological strategy to reduce ischemic complications of PCI was the use of parenteral glycoprotein (GP) IIb/IIIa inhibitors. The benefit of GP IIb/IIIa inhibitors in early studies was driven primarily by reductions in periprocedural myocardial infarction. Advances in both stent design and adjunct pharmacology have led to improved outcomes in ACS and a diminished role for GP IIb/IIIa inhibitors as reflected in current PCI guidelines. Current medical therapy with aspirin, clopidogrel, ticagrelol, prasugrel, and heparin provides important therapeutic benefits. The platelet GP IIb/IIIa receptor antagonists, by blocking the final common pathway of platelet aggregation, are a breakthrough in the management of ACS. Several large multicenter trials have evaluated the platelet GP IIb/IIIa antagonists with and without heparin undergoing PCI or not. There was a significantly reduced incidence in the cardiac ischemic events. The clinically important benefit persisted at 3 years of followup. In addition to maintaining epicardial wall vessel patency, it was shown an improvement in microvascular perfusion and myocardial function as assessed by peak coronary flow velocity and regional wall motion. Despite the success of abciximab in preventing ischemic events after PCI, the use of intravenous, small-molecule GP IIb/IIIa antagonists, and the intention to broaden the clinical indication have produced varied results. Mechanisms contributing to these heterogeneous outcomes may include the possibility of prothrombotic events, as well as, normal variation in platelet or receptor number, differences in receptor activity, and interpatient variation in pharmacological dose response. Trials investigating the role of intravenous small-molecule GP IIb/IIIa antagonists underline the importance of adequate higher and effective dosing. These trials highlight the use of suboptimal dose as the cause for the poor outcome in some instances. Despite the heterogeneous outcome, these agents still have potential advantages in patients with high clinical risk but low bleeding risk. Adjunctive platelet GP IIb/IIIa receptor inhibition has proved beneficial effects in the setting of PCI, and still has a place as bailout therapy for periprocedural PCI complications in ACS patients, such as those patients with large thrombus, with stent thrombosis, and refractory no-reflow phenomenon following PCI.