Abstract
Plaque rupture and vascular thrombosis are key initiating factors in the pathogenesis of ischemic complications of percutaneous coronary revascularization (1,2). The central role of platelet activity in this setting is highlighted by the unequivocal benefit of aspirin in preventing death or myocardial infarction among patients undergoing coronary intervention (3). Newer strategies for more potent inhibition of platelet activity at the injured coronary plaque focus on the integrin glycoprotein (GP) Ilb/IIIa receptor on the platelet surface membrane, which binds circulating fibrinogen or von Willebrand factor and crosslinks adjacent platelets as the final common pathway to platelet aggregation (4). Pharmacologic compounds directed against GP IIb/IIIa block this receptor, prevent binding of circulating adhesion molecules, and potently inhibit platelet aggregation.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Steele PM, Chesebro JH, Stanson AW, Holmes DR, Dewanjee MK, Badimon L, Fuster V. Balloon angioplasty. Natural history of the pathophysiological response to injury in a pig model. Circ Res 1985; 57: 105–112.
Uchida Y, Hasegawa K, Kawamura K, Shibuya I. Angioscopic observation of the coronary lumina’ changes induced by percutaneous transluminal coronary angioplasty. Am Heart J 1989; 117: 769–776.
Schwartz L, Bourassa MG, Lesperance J, Aldridge HE, Kazim F, Salvatori VA, Henderson M, Bonan R, David PR. Aspirin and dipyridamole in the prevention of restenosis after percutaneous transluminal coronary angioplasty. N Engl J Med 1988; 318: 1714–1719.
Phillips DR, Charo IF, Parise LV, Fitzgerald LA. The platelet membrane glycoprotein IIb/IIIa complex. Blood 1988; 71: 831–843.
Coller BS. Blockade of platelet GPIIb/IIIa receptors as an antithrombotic strategy. Circulation 1995; 92: 2373–2380.
Tcheng JE, Ellis SG, George BS, Kereiakes DJ, Kleiman NS, Talley JD, Wang AL, Weisman HF, Califf RM, Topol EJ. Pharmacodynamics of chimeric glycoprotein IIb/IIIa integrin antiplatelet antibody Fab 7E3 in high-risk coronary angioplasty. Circulation 1994; 90: 1757–1764.
Kleiman NS, Raizner AE, Jordan R, Wang AL, Norton D, Mace KF, Joshi A, Coller BS, Weisman HF. Differential inhibition of platelet aggregation induced by adenosine diphosphate or a thrombin receptor-activating peptide in patients treated with bolus chimeric 7E3 Fab: implications for inhibition of the internal pool of GPIIb/IIIa receptors. J Am Coll Cardiol 1995; 26: 1665–1671.
Mascelli MA, Lance ET, Damaraju L, Wagner CL, Weisman HF, Jordan RE. Pharmacodynamic profile of short-term abciximab treatment demonstrates prolonged platelet inhibition with gradual recovery from GP IIb/IIIa receptor blockade. Circulation 1998; 97: 1680–1688.
Harrington RA, Kleiman NS, Kottke-Marchant K, Lincoff AM, Tcheng JE, Sigmon KN, Joseph D, Rios G, Trainor K, Rose D, Greenberg CS, Kitt MM, Topol EJ, Califf RM. Immediate and reversible platelet inhibition after intravenous administration of a peptide glycoprotein IIb/IIIa inhibitor during percutaneous coronary intervention. Am J Cardiol 1995; 76: 1222–1227.
Kereiakes DJ, Kleiman NS, Ambrose J, Cohen M, Rodriguez S, Palabrica T, Herrmann HC, Sutton JM, Weaver WD, McKee DB, Fitzpatrick V, Sax FL. Randomized, double-blind, placebo-controlled dose-ranging study of tirofiban (MK-383) platelet IIb/IIIa blockade in high risk patients undergoing coronary angioplasty. J Am Coll Cardiol 1996; 27: 536–542.
EPIC Investigators. Use of a monoclonal antibody directed against the platelet glycoprotein IIb/IIIa receptor in high-risk coronary angioplasty. N Engl J Med 1994; 330: 956–961.
Lincoff AM, Tcheng JH, Califf RM, Bass TA, Popma JJ, Teirstein PS, Kleiman NS, Hattel LJ, Anderson HV, Ferguson JJ, Cabot CF, Anderson KM, Berdan LG, Musco MH, Weisman HF, Topol EJ, for the PROLONG Investigators. Standard versus low dose weight-adjusted heparin in patients treated with the platelet glycoprotein IIb/IIlareceptor antibody fragment abciximab (c7E3 Fab) during percutaneous coronary revascularization. Am J Cardiol 1997; 79: 286–291.
The EPILOG Investigators. Platelet glycoprotein IIb/IIIa blockade with abciximab with low-dose heparin during percutaneous coronary revascularization. N Engl J Med 1997; 336: 1689–1696.
The EPISTENT Investigators. Randomised placebo-controlled and balloon-angioplasty controlled trial to assess safety of coronaryt stenting with use of platelet glycoprotein IIb/IIIa blockade. Lancet 1998; 352: 87–92.
The IMPACT II Investigators. Randomized placebo-controlled trial of effect of eptifibatide on complications of percutaneous coronary intervention: IMPACT II. Lancet 1997; 349: 1422–1428.
The RESTORE Investigators. Effects of platelet glycoprotein IIb/IIIa blockade with tirofiban on adverse cardiac events in patients with unstable angina or acute myocardial infarction undergoing coronary angioplasty. Circulation 1997; 96: 1445–1453.
The CAPTURE Investigators. Randomised placebo-controlled trial of abciximab before and during coronary intervention in refractory unstable angina: the CAPTURE Study. Lancet 1997; 349: 1429–1435.
Brener SJ, Barr LA, Burchenal JEB, Katz S, George BS, Jones AA, Cohen ED, Gainey PC, White HJ, Cheek HB, Moses JW, Moliterno DJ, Effron MB, Topol EJ, on behalf of the ReoPro and Primary PTCA Organization and Randomized Trial (RAPPORT) Investigators. A randomized, placebo-controlled trial of platelet glycoprotein IIb/IIIa blockade with primary angioplasty for acute myocardial infarction. Circulation 1998; 98: 734–741.
Lincoff AM, Califf RM, Anderson KM, Weisman HF, Aguirre FV, Kleiman NS, Harrington RA, Topol EJ. Evidence for prevention of death and myocardial infarction with platelet membrane glycoprotein IIb/IIIa receptor blockade by c7E3 Fab (abciximab) among patients with unstable angina undergoing percutaneous coronary revascularization. J Am Coll Cardiol 1997; 30: 149–156.
Rao AK, Pratt C, Berke A, Jaffe A, Ockene I, Schreiber TL, Bell WR, Knatterud G, Robertson TL, Turin ML, for TIMI Investigators. Thrombolysis in myocardial infarction (TIMI) trial-Phase I: Hemorrhagic manifestations and changes in plasma fibrinogen and the fibrinolytic system in patients treated with recombinant tissue plasminogen activator and streptokinase. J Am Coll Cardiol 1988; 11: 1–11.
Abdelmeguid AE, Topol EJ, Whitlow PL, Sapp SK, Ellis SG. Significance of mild transient release of creatine kinase-MB fraction after percutaneous coronary intervention. Circulation 1996; 94: 1528–1536.
Kugelmass AD, Cohen CJ, Moscucci M, Piana RN, Senerchia C, Kuntz RE, Baim DS. Elevation in creatine kinase myocardial isoform following otherwise successful directional coronary atherectomy and stenting. Am J Cardiol 1994; 74: 748–754.
Harrington RA, Lincoff AM, Califf RM, Holmes DR, Berdan LG, O’ Hanesian MA, Keeler GP, Garratt KN, Ohman EM, Mark DB, Jacobs AK, Topol EJ, for the CAVEAT investigators. Characteristics and consequences of myocardial infarction after percutaneous coronary intervention: insights from the coronary angioplasty versus excisional atherectomy trial (CAVEAT). JACC 1995; 25: 1693–1699.
Kong TQ, Davidson CJ, Meyers SN, Tauke JT, Parker MA, Bonow RO. Prognostic implication of creatine kinase elevation following elective coronary artery interventions. JAMA 1997; 277: 461–466.
Tardiff BE, Califf RM, Tcheng JE, Lincoff AM, Sigmon KN, Harrington RA, Mahaffey KW, Teirstein P, Heinsimer J, Topol EJ, for the IMPACT-II Investigators. Post-intervention cardiac enzyme elevations: prognostic significance in IMPACT II. J Am Coll Cardiol 1996; 27: 83A (abstr.).
Redwood SR, Popma JJ, Kent KK, Pichard AD, Satler LF, Mintz GS, Hong MK, Bucher TA, Merritt AJ, Leon MB. Predictors of late mortality following ablative new-device angioplasty in native coronary arteries. J Am Coll Cardiol 1996; 27: 167A (abstr).
Topol EJ, Ferguson JJ, Weisman HF, Tcheng JE, Ellis SG, Kleiman NS, Ivanhoe RJ, Wang AL, Miller DP, Anderson KM, Califf RM, for the Epic Investigator Group. Long-term protection from myocardial ischemic events in a randomized trial of brief integrin 433 blockade with percutaneous coronary intervention. JAMA 1997; 278: 479–484.
Kereiakes DJ, Lincoff AM, Miller DP, Tcheng JE, Cabot CF, Anderson KM, Weisman HF, Califf RM, Topol EJ, for the EPILOG Investigators. Abciximab therapy and unplanned coronary stent deployment. Favorable effects on stent use, clinical outcomes, and bleeding complications. Circulation 1998; 97: 857–864.
Carrozza JP, Kuntz RE, Fishman RF, Baims DS. Restenosis after arterial injury caused by coronary stenting in patients with diabetes mellitus. Ann Int Med 1993; 118: 344–349.
Kornowski R, Mintz GS, Kent KM, Pichard AD, Satler LF, Bucher TA, Hong MK, Popma JJ, Leon MB. Increased restenosis in diabetes mellitus after coronary interventions is due to exaggerated intimal hyperplasia. A serial intravascular ultrasound study. Circulation 1997; 95: 1366–1369.
The PURSUIT Trial Investigators. Inhibition of platelet glycoprotein IIb/IIIa with eptifibatide in patients with acute coronary syndromes. N Engl J Med 1998; 339: 436–443.
The PRISM PLUS Study Investigators. Inhibition of the platelet glycoprotein IIb/IIIa receptor with tirofiban in unstable angina and non-Q-wave myocardial infarction. N Engl J Med 1998; 338: 1488–1497.
Kleiman NS, Lincoff AM, Kereiakes DJ, Miller DP, Aguirre FV, Anderson KM, Weisman HF, Califf RM, Topol EJ, for the EPILOG Investigators. Diabetes mellitus, glycoprotein IIb/IIIa blockade, and heparin. Evidence of a complex interaction in a multicenter trial. Circulation 1998; 97: 1912–1920.
Ghaffari S, Kereiakes DJ, Lincoff AM, Kelly TA, Timmis GC, Kleiman NS, Ferguson JJ, Miller DP, Califf RA, Topol EJ, for the EPILOG Investigators. Platelet glycoprotein IIb/IIIa receptor blockade with abciximab reduces ischemic complications in patients undergoing directional coronary atherectomy. Am J Cardiol 1998; 82: 7–12.
Reverter JC, Beguin S, Kessels H, Kumar R, Hemker HC, Coller BS. Inhibition of platelet-mediated, tissue factor-induced thrombin generation by the mouse/human chimeric 7E3 antibody. J Clin Invest 1996; 98: 863–874.
Phillips DR, Teng W, Arfstent A, Nannizzi-Alaimo L, White MM, Longhurst C, Shattil SJ, Randolph A, Jakubowski JA, Jennings LK, Scarborough RM. Effect of Ca2+on GP IIb-IIIa interactions with Integrilin. Enhanced GP IIb-IIIa binding and inhibition of platelet aggregation by reductions in the concentration of ionized calcium in plasma anticoagulated with citrate. Circulation 1997; 96: 1488–1494.
Wagner CL, Cunningham MR, Wyand MS, Weisman HF, Coller BS, Jordan RE. Reversal of the antiplatelet effects of chimeric 7E3 Fab treatment by platelet transfusion in cynomolgous monkeys. Thromb Haemost 1995; 73: 1313 (abstr.).
Juergens CP, Yeung AC, Oesterle SN. Routine platelet transfusion in patients undergoing emergency coronary bypass surgery after receiving abciximab. Am J Cardiol 1997; 80: 74–75.
Boehrer JD, Kereiakes DJ, Navetta FI, Califf RM, Topol EJ, for the EPIC investigators. Effects of profound platelet inhibition with c7E3 before coronary angioplasty on complications of coronary bypass surgery. Am J Cardiol 1994; 74: 1166–1170.
Berkowitz SD, Harrington RA, Rund MM, Tcheng JE. Acute profound thrombocytopenia after c7E3 Fab (abciximab) therapy. Circulation 1997; 95: 809–813.
Tcheng JE, Kereiakes DJ, Braden GA, Lincoff AM, Mascelli MA, Langra MA, Damaraju LV, Schantz AR, Barnathan ES, Effron MB. Safety of abciximab retreatment-final clinical report of the ReoPro Readministration Registry (R3) (abstr.). Circulation 1998; 98: 1–17.
Mark DB, Talley JD, Topol EJ, Bowman L, Lam LC, Anderson KM, Jollis JG, Cleman MW, Lee KL, Aversano T, Untereker WJ, Davidson-Ray L, Califf RM, for the EPIC Investigators. Economic assess-ment of platelet glycoprotein IIb/IIIa inhibition for prevention of ischemic complications of high-risk coronary angioplasty. Circulation; 1996; 94: 629–635.
Muhlestein JB, Karagounis LA, Treehan S, Anderson JL. “Rescue” utilization of abciximab for the dissolution of coronary thrombus developing as a complication of coronary angioplasty. J Am Coll Cardiol 1997; 30: 1729–1734.
Lucore CL, Trask RV, Mishkel GJ, Kacich, RL, Rocha-Singh KJ, Moses HW, Mikell FL, Shelton MD, Ligon RW. Impact of abciximab and stents on outcomes and economics in a community hospital. J Am Coll Cardiol 1998; 31: 200A (abstr.).
Ellis SG, Vandormael MG, Cowley MJ, DiSciascio G, Deligonul U, Topol EJ, Bulle TM. Coronary morphologic and clinical determinants of procedural outcome with angioplasty for multivessel coronary disease. Implications for patient selection. Circulation 1990; 82: 1193–1202.
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1999 Springer Science+Business Media New York
About this chapter
Cite this chapter
Lincoff, A.M., Topol, E.J. (1999). Overview of the Glycoprotein IIb/IIIa Inhibitor Interventional Trials. In: Lincoff, A.M., Topol, E.J. (eds) Platelet Glycoprotein IIb/IIIa Inhibitors in Cardiovascular Disease. Contemporary Cardiology. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-59259-724-6_9
Download citation
DOI: https://doi.org/10.1007/978-1-59259-724-6_9
Publisher Name: Humana Press, Totowa, NJ
Print ISBN: 978-1-4757-6202-0
Online ISBN: 978-1-59259-724-6
eBook Packages: Springer Book Archive