Full Description
One of the most important developments in the field of cardiovascular medicine over the last two decades has been recognition of the key role played by arterial thrombosis in the pathogenesis of acute coronary syndromes, ischemic complications of percutane- ous coronary revascularization, and coronary and peripheral atherosclerosis. The phar- macologic armamentarium directed against vascular thrombosis has thus expanded substantially during that time, with development of new fibrinolytic agents, low-molecu- lar-weight heparins, direct thrombin inhibitors, antagonists to platelet activation, and the platelet glycoprotein lIb/IlIa inhibitors. Though clinical investigations of these com- pounds have been marked by failures as well as successes, there is little doubt that enhanced antithrombotic therapies have markedly improved the outcome of patients undergoing coronary revascularization or with acute coronary syndromes. Glycoprotein IIblIlIa receptor antagonists were introduced into clinical practice to overcome the limitations of approaches that inhibit only individual pathways of platelet activation.
Multiple mechanisms of platelet activation in response to different agonists converge on the platelet membrane glycoprotein IIblIlIa complex, the "final common pathway" of platelet aggregation. The clinical hemorrhagic syndrome caused by a rare inherited defect in this receptor (Glanzmann' s thrombasthenia), characterized by muco- cutaneous and postsurgical bleeding, but infrequent spontaneous organ (particularly central nervous system) bleeding, suggested that therapeutic inhibition of this receptor might be a potent, yet well-tolerated means of treating thrombotic disorders.
Contents
1 Thrombosis in Acute Coronary Syndromes and Coronary Interventions.- 2 Platelet Adhesion.- 3 Glycoprotein IIb/IIIa in Platelet Aggregation and Acute Arterial Thrombosis.- 4 Glycoprotein IIb/IIIa Antagonists: Development of Abciximab and Pharmacology of Abciximab, Tirofiban, and Eptifibatide.- 5 Abciximab During Percutaneous Coronary Intervention: EPIC, EPILOG, and EPISTENT Trials.- 6 Eptifibatide in Coronary Intervention: The IMPACT and ESPRIT Trials.- 7 Tirofiban in Interventional Cardiology: The RESTORE and TARGET Trials.- 8 Overview of the Glycoprotein IIb/Illa Interventional Trials.- 9 The Use of Abciximab in Therapy-Resistant Unstable Angina: Clinical and Angiographic Results of the CAPTURE Pilot Trial and the CAPTURE Study.- 10 Unstable Angina Trials: PARAGON, PURSUIT, PRISM, PRISM-PLUS, and GUSTO-IV.- 11 Platelet Glycoprotein IIb/IIIa Inhibitors and an Invasive Strategy.- 12 Glycoprotein IIb/IIIa Receptor Blockade in Myocardial Infarction: Adjunctive Therapy to Percutaneous Coronary Interventions.- 13 Glycoprotein IIb/IIIa Receptor Blockade in Acute Myocardial Infarction: Adjunctive Therapy to Fibrinolysis.- 14 Economics of Glycoprotein IIb/IIIa Inhibition.- 15 Platelet Monitoring and Interaction of Glycoprotein IIb/IIIa Antagonists with Other Antiplatelet Agents.- 16 Platelet Glycoprotein IIb/IIIa Antagonists: Their Interaction with Low-Molecular-Weight Heparins and Direct Thrombin Inhibitors.- 17 Oral Agents.- 18 Platelet Glycoprotein IIb/IIIa Inhibitors: Effects Beyond the Platelet.- 19 Cerebrovascular Interventions.- 20 Cerebrovascular Aspects of Glycoprotein IIb/IIIa Receptor Inhibitors.- 21 Evolution of Drug Development in Evidence-Based Medicine: Summary and the Future.
