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Glycoprotein IIb/IIIa antagonists - from bench to practice
Authors:I P Casserly  E J Topol
Institution:(1) Department of Cardiovascular Medicine, Desk F25, Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195 (USA), Fax + 1 216 445 9594, e-mail: topole@ccf.org , US;(2) Present address: Department of Cardiology, Washington University School of Medicine, Barnes Jewish Hospital, St Louis (USA),
Abstract:The central role played by the αIIbβ3 receptor in platelet aggregation, and hence in platelet thrombosis, has led to the development of a number of parenteral and oral glycoprotein (GP) IIb/IIIa inhibitors for use in cardiovascular disease states, such as acute coronary syndromes and stroke. The predominant effect of these agents is to inhibit platelet aggregation, although studies of αIIbβ3 receptor function and various GP IIb/IIIa inhibitors have demonstrated the potential for these agents to produce effects on other aspects of platelet function, in addition to non-platelet effects. Overall, clinical studies have demonstrated an impressive beneficial effect for parenteral agents in reducing ischemic complications following percutaneous intervention, and a more modest beneficial effect in the treatment of patients with acute coronary syndromes. Trials with oral GP IIb/IIIa inhibitors in similar patient populations have demonstrated toxicity, manifested by an increased mortality in treated patients. Increased understanding of molecular aspects of both αIIbβ3 receptor function and the effects of GP IIb/IIIa inhibition may help explain some of the inconsistency in recently reported clinical studies with parenteral agents, and the frank toxicity of oral agents. Such studies may also hold the key to the development of newer agents with enhanced therapeutic benefit. Received 10 September 2001; received after revision 22 October 2001; accepted 2 November 2001
Keywords:, Platelet, thrombosis, α,IIbβ,3 receptor, glycoprotein IIb/IIIa inhibitor, acute coronary syndrome, myocardial infarction,,,,,,percutaneous intervention,
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