Platelet glycoprotein IIb/IIIa receptor antagonists in cardiovascular disease.

CONTEXT Thrombus formation on disrupted atherosclerotic plaque is the major cause of acute coronary events. Platelet inhibitors are the mainstay of drug therapy to reduce cardiac events in patients with acute coronary syndromes. The platelet glycoprotein (GP) IIb/IIIa receptor is the final common pathway of platelet aggregation. OBJECTIVES To review mechanisms of platelet activation and aggregation and the role of the GP IIb/IIIa receptor in the acute coronary syndromes and to summarize completed clinical trials of GP IIb/IIIa receptor antagonists. DATA SOURCES English-language journal articles, reviews from a MEDLINE search from 1993 through 1998, as well as abstracts and presentations from major national or international cardiology meetings through November 1998. STUDY SELECTION/DATA EXTRACTION Randomized, placebo-controlled clinical trials testing intravenous GP IIb/IIIa receptor antagonists and having more than 500 subjects were included. Data quality and validity included publication or presentation venue. DATA SYNTHESIS/CONCLUSIONS: The GP IIb/IIIa receptor is the final common pathway of platelet aggregation. Intravenous monoclonal antibody and peptide and nonpeptide antagonists of the GP IIb/IIIa receptor have been tested in randomized, placebo-controlled trials of the acute coronary syndromes and percutaneous coronary interventions. For patients undergoing percutaneous revascularization, these agents have demonstrated efficacy in reducing death, myocardial infarction, or urgent reintervention. Odds ratios of death or myocardial infarction at 30 days range from 0.42 to 0.84 for the drugs in these studies. More modest benefits have been seen in trials of IIb/IIIa receptor antagonists for patients with the acute coronary syndromes, with odds ratios for death or myocardial infarction at 30 days ranging from 0.70 to 0.89. The efficacy of oral agents for chronic GP IIb/IIIa receptor antagonism has not been sufficiently studied.