Overview of clinical trials of glycoprotein IIb-IIIa inhibitors in acute coronary syndromes.
Acute coronary syndromes (ACS) are the major cause of mortality and morbidity in Western countries. The primary pathophysiologic mechanism of ACS involves the formation of thrombus in coronary arteries in response to spontaneous or intervention-induced endothelial damage. This leads to myocardial ischemia. The final common pathway to the coronary thrombosis underlying ACS involves the aggregation of platelets mediated by the binding of soluble fibrinogen to the platelet receptor glycoprotein (GP) IIb-IIIa. Several GP IIb-IIIa inhibitors have been developed that promise greater antithrombotic potential than aspirin and heparin alone. Over the past 2 years, 4 major trials involving more than 18,000 patients have evaluated the therapeutic potential of 3 small-molecule, intravenous GP IIb-IIIa inhibitors as a component of first-line management of unstable angina or non-ST-segment elevation myocardial infarction. Results of these studies show that administration of a GP IIb-IIIa inhibitor in combination with aspirin and heparin provides a significant reduction in mortality and morbidity rates compared with aspirin plus heparin alone. Recent approvals of 2 GP IIb-IIIa inhibitors, the peptide eptifibatide and the peptidomimetic tirofiban, mark the beginning of a new era in the management of non-ST-segment elevation ACS.
Harrington
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Duke Clinical Research Institute, Durham, NC 27705, USA. harri019@mc.duke.edu
D000208:Acute Disease; D000925:Anticoagulants / Q000627:therapeutic use; D001241:Aspirin / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D003327:Coronary Disease / Q000188:drug therapy* / Q000503:physiopathology; D003328:Coronary Thrombosis / Q000150:complications / Q000503:physiopathology; D000077542:Eptifibatide; D005343:Fibrinolytic Agents / Q000627:therapeutic use; D006493:Heparin / Q000627:therapeutic use; D006801:Humans; D017202:Myocardial Ischemia / Q000209:etiology; D010455:Peptides / Q000627:therapeutic use; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000037:antagonists & inhibitors*; D000077466:Tirofiban; D014443:Tyrosine / Q000031:analogs & derivatives / Q000627:therapeutic use
D000925:Anticoagulants; D005343:Fibrinolytic Agents; D010455:Peptides; D010975:Platelet Aggregation Inhibitors; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D014443:Tyrosine; D006493:Heparin; D000077466:Tirofiban; D000077542:Eptifibatide; D001241:Aspirin