Download PDF
Thromb Haemost 2001; 86(01): 427-443
DOI: 10.1055/s-0037-1616241
Research Article
Schattauer GmbH

Anti-GPIIb/IIIa Drugs: Current Strategies and Future Directions

Barry S. Coller
1   Mount Sinai School of Medicine, New York, USA
› Author AffiliationsI would like to acknowledge research support grants N°19278 and N°54469 from the National Heart, Lung and Blood Institute of NIH. I also would like to thank Suzanne Rivera for outstanding secretarial assistance.
Further Information

Publication History

Publication Date:
12 December 2017 (online)

    Permissions and Reprints

Summary

Three platelet glycoprotein (GP) IIb/IIIa receptor antagonists have been approved as adjunctive therapy to decrease the ischemic complications of percutaneous coronary interventions (PCI) and/or unstable angina. They include the chimeric murine/human monoclonal antibody 7E3 Fab fragment (abciximab), a cyclic heptapeptide based on the KGD amino acid sequence (eptifibatide), and a nonpeptide mimetic of the RGD sequence (tirofiban). The agents are very effective in providing both short-term and long-term benefit after PCI, and one agent has also demonstrated a progressive long-term mortality benefit. The long-term mortality benefit is highly cost-effective when compared to other medical interventions. The benefits in treating unstable angina without PCI are less dramatic and robust, with some agents providing no benefit. Severe thrombocytopenia is an infrequent, but potentially serious, complication of therapy with all of the agents. The risk of major bleeding is increased only minimally or not at all by the drugs. Currently, a number of new indications for GPIIb/IIIa antagonists are under study, including acute myocardial infarction (± thrombolytic therapy, ± PCI) and stroke. In addition to their impact on improving outcome, the results of clinical trials with these agents provide crucial insights into the contribution of GPIIb/IIIa-mediated platelet function in the pathophysiology of thrombotic vascular disease.

Key words

Abciximab - tirofiban - eptifibatide - angioplasty - unstable angina - antithrombotic therapy
 

  • References

  • 1 Coller BS. Binding of abciximab to αvβ3 and activated M 2 receptors: with a review of platelet-leukocyte interactions. Thromb Haemost 1999; 82: 326-36.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 2 Coller BS. Platelet GPIIb/IIIa antagonists: The first anti-integrin receptor therpaeutics. J Clin Invest 1997; 99: 1467-71.
    CrossrefPubMedGoogle Scholar
  • 3 Coller BS. GPIIb/IIIa antagonists: development of abciximab and pharmacology of select agents. In: Lincoff AM, Topol EJ. editors. Glycoprotein IIb/IIIa Inhibitors in Cardiology. Humana Press; 1998: 67-89.
    Google Scholar
  • 4 Scarborough RM. Development of eptifibatide. Am Heart J 1999; 138: 1093-104.
    CrossrefPubMedGoogle Scholar
  • 5 Glycoprotein IIb/IIIa Inhibitors in Cardiology. Lincoff AM, Topol EJ. editors. Humana Press; 1998
    Google Scholar
  • 6 Lincoff AM, Califf RM, Topol EJ. Platelet glycoprotein IIb/IIIa receptor blockade in coronary artery disease. J Am Coll Cardiol 2000; 35: 1103-15.
    CrossrefPubMedGoogle Scholar
  • 7 Bhatt DL, Topol EJ. Current role of platelet glycoprotein IIb/IIIa inhibitors in acute coronary syndromes. JAMA 2000; 284: 1549-58.
    CrossrefPubMedGoogle Scholar
  • 8 Jordan RE, Wagner CL, Mascelli M, Treacy G, Nedelman MA, Woody JN. et al. Preclinical development of c7E3 Fab; a mouse/human chimeric monoclonal antibody fragment that inhibits platelet function by blockade of GPIIb/IIIa receptors with observations on the immunogenicity of c7E3 Fab in humans. In: Horton MDMA. editor. Adhesion Receptors as Therapeutic Targets. Boca Raton: CRC Press Inc; 1996: 281-305.
    Google Scholar
  • 9 Tam SH, Sassoli PM, Jordan RE, Nakada MT. Abciximab (ReoPro, chimeric 7E3 Fab) demonstrates equivalent affinity and functional blockade of glycoprotein IIb/IIIa and alpha(v)beta3 integrins. Circulation 1998; 98: 1085-91.
    CrossrefPubMedGoogle Scholar
  • 10 Steinhubl SR, Kottke-Marchant K, Moliterno DJ, Rosenthal ML, Godfrey NK, Coller BS. et al. Attainment and maintenance of platelet inhibition through standard dosing of abciximab in diabetic and nondiabetic patients undergoing percutaneous coronary intervention. Circulation 1999; 100: 1977-82.
    CrossrefPubMedGoogle Scholar
  • 11 Nurden P, Poujol C, Durrieu-Jais C, Winckler J, Combrie R, Macchi L. et al. Labeling of the internal pool of GP IIb-IIIa in platelets by c7E3 Fab fragments (abciximab): flow and endocytic mechanisms contribute to the transport. Blood 1999; 93: 1622-33.
    PubMedGoogle Scholar
  • 12 Poujol C, Durrieu-Jais C, Larrue B, Nurden AT, Nurden P. Accessibility of abciximab to megakaryocytes and endothelial cells in the bone marrow compartment: studies on a patient receiving antithrombotic therapy. Br J Haematol 1999; 107: 526-31.
    CrossrefPubMedGoogle Scholar
  • 13 Masse JM, Perlemuter K, Debili N, Letestu R, Castaigne A, Cramer EM. Intracellular trafficking of the alphaIIbbeta3 receptor antagonist, abciximab, in normal and Glanzmann’s disease megakaryocytes. Br J Haematol 1999; 107: 720-30.
    CrossrefPubMedGoogle Scholar
  • 14 Kohl DW, Slavik KJ, Kamath G, Lehr JM, McDonald MJ, Rubio F. High-dose abciximab during coronary angioplasty in a patient with essential thrombocytosis. J Invasive Cardiol 1998; 10: 173-6.
    PubMedGoogle Scholar
  • 15 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: 1680-8.
    CrossrefPubMedGoogle Scholar
  • 16 Wagner CL, Cunningham MR, Wyand MS, Weisman HF, Coller BS, Jordan RE. Reversal of the anti-platelet effects of chimeric 7E3 Fab treatment by platelet transfusion in cynomolgus monkeys. Thromb Haemost 1995; 73: 1313a (abstr.).
    PubMedGoogle Scholar
  • 17 Coller BS, Seligsohn U, Zivelin A, Zwang E, Lusky A, Modan M. Immunologic and biochemical characterization of homozygous and heterozygous Glanzmann’s thrombasthenia in Iraqi-Jewish and Arab populations of Israel: Comparison of techniques for carrier detection. Br J Haematol 1986; 62: 723-35.
    CrossrefPubMedGoogle Scholar
  • 18 Phillips DR, Teng W, Arfsten A, Nannizzi-Alaimo L, White MM, Longhurst C. et al. Effect of Ca2+ on GPIIb-IIIa interactions with integrilin: Enhanced GPIIb-IIIa binding and inhibition of platelet aggregation by reductions in the concentration of ionized calicum in plasma anticoagulated with citrate. Circulation 1997; 96: 1488-94.
    CrossrefPubMedGoogle Scholar
  • 19 Kereiakes DJ, Broderick TM, Roth EM, Whang D, Shimshak T, Runyon JP. et al. Time course, magnitude, and consistency of platelet inhibition by abciximab, tirofiban, or eptifibatide in patients with unstable angina pectoris undergoing percutaneous coronary intervention. Am J Cardiol 1999; 84: 391-5.
    CrossrefPubMedGoogle Scholar
  • 20 Hartman GD, Egbertson MS, Halczenko W, Laswell WL, Duggan ME, Smith RL. et al. Non-peptide fibrinogen receptor antagonists. 1. Discovery and design of exosite inhibitors. J Med Chem 1992; 35: 4640-2.
    CrossrefPubMedGoogle Scholar
  • 21 Egbertson MS, Chang CT, Duggan ME, Gould RJ, Halczenko W, Hartman GD. et al. Non-peptide fibrinogen receptor antagonists. 2. Optimization of a tyrosine template as a mimic for Arg-Gly-Asp. J Med Chem 1994; 37: 2537-51.
    CrossrefPubMedGoogle Scholar
  • 22 Barrett JS, Murphy G, Peerlinck K, De Lepeleire I, Gould RJ, Panebianco D. et al. Pharmacokinetics and pharmacodynamics of MK-383, a selective non- peptide platelet glycoprotein-IIb/IIIa receptor antagonist, in healthy men. Clin Pharmacol Ther 1994; 56: 377-88.
    CrossrefPubMedGoogle Scholar
  • 23 Peerlinck K, De Lepeleire I, Goldberg M, Farrell D, Barrett J, Hand E. et al. MK-383 (L-700,462), a selective nonpeptide platelet glycoprotein IIb/IIIa antagonist, is active in man. Circulation 1993; 88: 1512-7.
    CrossrefPubMedGoogle Scholar
  • 24 Kereiakes DJ, Kleiman NS, Ambrose J, Cohen M, Rodriguez S, Palabrica T. et al. 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: 536-42.
    CrossrefPubMedGoogle Scholar
  • 25 Vickers S, Theoharides AD, Arison B, Balani SK, Cui D, Duncan CA. et al. In vitro and in vivo studies on the metabolism of tirofiban. Drug Metab Dispos 1999; 27: 1360-6.
    PubMedGoogle Scholar
  • 26 Chew DP, Moliterno DJ. A critical appraisal of platelet glycoprotein IIb/IIIa inhibition. J Am Coll Cardiol 2000; 36: 2028-35.
    CrossrefPubMedGoogle Scholar
  • 27 Anderson KM, Weisman HF, Coller BS. Platelet glycoprotein IIb/IIIa receptor inhibitors. In: Hennekens CH. editor. Clinical Trials in Cardiovascular Disease. Philadelphia: WB Saunders; 1999: 166-83.
    Google Scholar
  • 28 Topol EJ, Mark DB, Lincoff AM, Cohen E, Jeffrey B, Kleiman N. et al. Outcomes at 1 year and economic implications of platelet glycoprotein IIb/IIIa blockade in patients undergoing coronary stenting: results from a multicentre randomised trial. Lancet 1999; 354: 2019-24.
    CrossrefPubMedGoogle Scholar
  • 29 Kereiakes DJ, Runyon JP, Broderick TM, Shimshak T. IIb’s are not IIb’s. Am J Cardiol 2000; 85: 23C-31.
    PubMedGoogle Scholar
  • 30 Mukherjee D, Reginelli JP, Moliterno DJ, Yadav JS, Schneider JP, Raymond R. et al. Unexpected mortality reduction with abciximab for in-stent restenosis. J Invasive Cardiol 2000; 12: 540-4.
    PubMedGoogle Scholar
  • 31 Marso SP, Lincoff AM, Ellis SG, Bhatt DL, Tanguay JF, Kleiman NS. et al. Optimizing the percutaneous interventional outcomes for patients with diabetes mellitus: Results of the EPISTENT (Evaluation of Platelet IIb/ IIIa Inhibitor for Stenting Trial) diabetic substudy. Circulation 1999; 100: 2477-84.
    CrossrefPubMedGoogle Scholar
  • 32 Bhatt DL, Marso SP, Lincoff AM, Wolski KE, Ellis SG, Topol EJ. Abciximab reduces mortality in diabetics following percutaneous coronary intervention. J Am Coll Cardiol 2000; 35: 922-8.
    CrossrefPubMedGoogle Scholar
  • 33 Topol EJ, Califf RM, Weismann HF, Ellis SG, Tcheng JE, Worley S. et al. Randomized trial of coronary intervention with antibody against platelet IIb/ IIIa integrin for reduction of clinical restenosis: results at six months. Lancet 1994; 343: 881-6.
    CrossrefPubMedGoogle Scholar
  • 34 Acute platelet inhibition with abciximab does not reduce in-stent restenosis (ERASER study).. The ERASER Investigators. Circulation 1999; 100: 799-806.
    CrossrefPubMedGoogle Scholar
  • 35 Neumann FJ, Kastrati A, Schmitt C, Blasini R, Hadamitzky M, Mehilli J. et al. Effect of glycoprotein IIb/IIIa receptor blockade with abciximab on clinical and angiographic restenosis rate after the placement of coronary stents following acute myocardial infarction. J Am Coll Cardiol 2000; 35: 915-21.
    CrossrefPubMedGoogle Scholar
  • 36 Prosser LA, Stinnett AA, Goldman PA, Williams LW, Hunink MG, Goldman L. et al. Cost-effectiveness of cholesterol-lowering therapies according to selected patient characteristics. Ann Intern Med 2000; 132: 769-79.
    PubMedGoogle Scholar
  • 37 Smeeton AH. Washington Post 1999 Aug 7.
    PubMed
  • 38 Boersma E, Akkerhuis KM, Theroux P, Califf RM, Topol EJ, Simoons ML. Platelet glycoprotein IIb/IIIa receptor inhibition in non-ST-elevation acute coronary syndromes: early benefit during medical treatment only, with additional protection during percutaneous coronary intervention. Circulation 1999; 100: 2045-8.
    CrossrefPubMedGoogle Scholar
  • 39 Hamm CW, Heeschen C, Goldmann B, Vahanian A, Adgey J, Miguel CM. et al. Benefit of abciximab in patients with refractory unstable angina in relation to serum troponin T levels. c7E3 Fab Antiplatelet Therapy in Unstable Refractory Angina (CAPTURE) Study Investigators. N Engl J Med 1999; 340: 1623-9.
    CrossrefPubMedGoogle Scholar
  • 40 Roe MT, Harrington RA, Prosper DM, Pieper KS, Bhatt DL, Lincoff AM. et al. Clinical and therapeutic profile of patients presenting with acute coronary syndromes who do not have significant coronary artery disease. The Platelet Glycoprotein IIb/IIIa in Unstable Angina: Receptor Suppression Using Integrilin Therapy (PURSUIT) Trial Investigators. Circulation 2000; 102: 1101-6.
    CrossrefPubMedGoogle Scholar
  • 41 Kragel AH, Gertz SD, Roberts WC. Morphologic comparison of frequency and types of acute lesions in the major epicardial coronary arteries in unstable angina pectoris, sudden coronary death and acute myocardial infarction. J Am Coll Cardiol 1991; 18: 801-8.
    CrossrefPubMedGoogle Scholar
  • 42 International, randomized, controlled trial of lamifiban (a platelet glycoprotein IIb/IIIa inhibitor), heparin, or both in unstable angina.. The PARAGON Investigators. Platelet IIb/IIIa Antagonism for the Reduction of Acute coronary syndrome events in a Global Organization Network. Circulation 1998; 97: 2386-95.
    CrossrefPubMedGoogle Scholar
  • 43 Holmes MB, Kabbani S, Watkins MW, Battle RW, Schneider DJ. Images in cardiovascular medicine. Abciximab-associated pseudothrombocytopenia. Circulation 2000; 101: 938-9.
    CrossrefPubMedGoogle Scholar
  • 44 Berkowitz SD, Harrington RA, Rund MM, Tcheng JE. Acute profound thrombocytopenia following c7E3 Fab (abciximab) therapy. Circulation 1997; 95: 809-13.
    CrossrefPubMedGoogle Scholar
  • 45 Berkowitz SD, Sane DC, Sigmon KN, Shavender JH, Harrington RA, Tcheng JE. et al. Occurrence and clinical significance of thrombocytopenia in a population undergoing high-risk percutaneous coronary revascularization. Evaluation of c7E3 for the Prevention of Ischemic Complications (EPIC) Study Group. J Am Coll Cardiol 1998; 32: 311-9.
    CrossrefPubMedGoogle Scholar
  • 46 Jubelirer SJ, Koenig BA, Bates MC. Acute profound thrombocytopenia following c7E3 Fab (Abciximab) therapy: case reports, review of the literature and implications for therapy. Am J Hematol 1999; 61: 205-8.
    CrossrefPubMedGoogle Scholar
  • 47 Curtis BR, McFarland JG, Garrity MM, Aster RH. Thrombocytopenia induced by abciximab: studies of pathogenesis. Blood 1998; 92 suppl 1 181a (abstr.).
    PubMedGoogle Scholar
  • 48 Peter K, Straub A, Kohler B, Volkmann M, Schwarz M, Kubler W. et al. Platelet activation as a potential mechanism of GP IIb/IIIa inhibitor-induced thrombocytopenia. Am J Cardiol 1999; 84: 519-24.
    CrossrefPubMedGoogle Scholar
  • 49 Jennings LK, Haga JH, Slack SM. Differential expression of a ligand induced binding site (LIBS) by GPIIb-IIIa ligand recognition peptides and parenteral antagonists. Thromb Haemost 2001; 84: 1095-102.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 50 Coto H. Platelet receptor glycoprotein IIb/IIIa inhibition with eptifibatide in a patient with thrombocytopenia after treatment with abciximab. J Invasive Cardiol 2000; 12: 528-31.
    PubMedGoogle Scholar
  • 51 Desai M, Lucore CL. Uneventful use of tirofiban as an adjunct to coronary stenting in a patient with a history of abciximab-associated thrombocytopenia 10 months earlier. J Invasive Cardiol 2000; 12: 109-12.
    PubMedGoogle Scholar
  • 52 Use of a monoclonal antibody directed against the platelet glycoprotein IIb/ IIIa receptor in high-risk coronary angioplasty.. The EPIC Investigation. N Engl J Med 1994; 330: 956-61.
    CrossrefPubMedGoogle Scholar
  • 53 Memon MA, Blankenship JC, Wood GC, Frey CM, Menapace FJ. Incidence of intracranial hemorrhage complicating treatment with glycoprotein IIb/IIIa receptor inhibitors: a pooled analysis of major clinical trials. Am J Med 2000; 109: 213-7.
    CrossrefPubMedGoogle Scholar
  • 54 Ali A, Patil S, Grady KJ, Schreiber TL. Diffuse alveolar hemorrhage following administration of tirofiban or abciximab: a nemesis of platelet glycoprotein IIb/IIIa inhibitors. Catheter Cardiovasc Interv 2000; 49: 181-4.
    CrossrefPubMedGoogle Scholar
  • 55 Lemmer Jr JH. Clinical experience in coronary bypass surgery for abciximab-treated patients. Ann Thorac Surg 2000; 70: S33-7.
    CrossrefPubMedGoogle Scholar
  • 56 Lincoff AM, LeNarz LA, Despotis GJ, Smith PK, Booth JE, Raymond RE. et al. Abciximab and bleeding during coronary surgery: results from the EPILOG and EPISTENT trials. Improve Long-term Outcome with abciximab GP IIb/IIIa blockade. Evaluation of Platelet IIb/IIIa Inhibition in STENTing. Ann Thorac Surg 2000; 70: 516-26.
    CrossrefPubMedGoogle Scholar
  • 57 Lemmer Jr JH, Metzdorff MT, Krause Jr AH, Martin MA, Okies JE, Hill JG. Emergency coronary artery bypass graft surgery in abciximab-treated patients. Ann Thorac Surg 2000; 69: 90-5.
    CrossrefPubMedGoogle Scholar
  • 58 Dyke CM. Safety of glycoprotein IIb-IIIa inhibitors: A heart surgeon’s perspective. Am Heart J 1999; 138: 307-16.
    CrossrefPubMedGoogle Scholar
  • 59 Raymond RE, Lincoff AM, Booth JE. Coronary bypass surgery within 12 h of administration of abciximab remains safe despite an increased risk of perioperative bleeding. European Heart J 1998; 19: 238a (abstr.).
    PubMedGoogle Scholar
  • 60 Madan M, Kereiakes DJ, Hermiller JB, Rund MM, Tudor G, Anderson L. et al. Efficacy of abciximab readministration in coronary intervention. Am J Cardiol 2000; 85: 435-40.
    CrossrefPubMedGoogle Scholar
  • 61 Tcheng JE, Kereiakes DJ, Braden GA, Jordan RE, Mascelli MA, Langrall MA. et al. Readministration of abciximab: interim report of the ReoPro readministration registry. Am Heart J 1999; 138: S33-8.
    CrossrefPubMedGoogle Scholar
  • 62 Arjomand H, Magsi ZM, Chang KS, Mascarenhas DA. Abciximab read-ministration: A single-operator community-hospital experience. Catheter Cardiovasc Interv 1999; 47: 294-6.
    CrossrefPubMedGoogle Scholar
  • 63 Novel dosing regimen of eptifibatide in planned coronary stent implantation (ESPRIT): a randomised, placebo-controlled trial.. The ESPRIT Investigators. Enhanced Suppression of the Platelet IIb/IIIa Receptor with Integrilin Therapy. Lancet 2000; 356: 2037-44.
    CrossrefPubMedGoogle Scholar
  • 64 Inhibition of platelet glycoprotein IIb/IIIa with eptifibatide in patients with acute coronary syndromes.. The PURSUIT Trial Investigators. Platelet Glycoprotein IIb/IIIa in Unstable Angina: Receptor Suppression Using Integrilin Therapy. N Engl J Med 1998; 339: 436-43.
    CrossrefPubMedGoogle Scholar
  • 65 Hasdai D, Harrington RA, Hochman JS, Califf RM, Battler A, Box JW. et al. Platelet glycoprotein IIb/IIIa blockade and outcome of cardiogenic shock complicating acute coronary syndromes without persistent ST-segment elevation. J Am Coll Cardiol 2000; 36: 685-92.
    CrossrefPubMedGoogle Scholar
  • 66 Mark DB, Harrington RA, Lincoff AM, Califf RM, Nelson CL, Tsiatis AA. et al. Cost-effectiveness of platelet glycoprotein IIb/IIIa inhibition with eptifibatide in patients with non-ST-elevation acute coronary syndromes. Circulation 2000; 101: 366-71.
    CrossrefPubMedGoogle Scholar
  • 67 Lincoff AM, Harrington RA, Califf RM, Hochman JS, Guerci AD, Ohman EM. et al. Management of patients with acute coronary syndromes in the United States by platelet glycoprotein IIb/IIIa inhibition. Insights from the platelet glycoprotein IIb/IIIa in unstable angina: receptor suppression using integrilin therapy (PURSUIT) trial. Circulation 2000; 102: 1093-100.
    CrossrefPubMedGoogle Scholar
  • 68 Akkerhuis KM, Deckers JW, Boersma E, Harrington RA, Stepinska J, Mahaffey KW. et al. Geographic variability in outcomes within an international trial of glycoprotein IIb/IIIa inhibition in patients with acute coronary syndromes. Results from PURSUIT. Eur Heart J 2000; 21: 371-81.
    CrossrefPubMedGoogle Scholar
  • 69 Marso SP, Bhatt DL, Roe MT, Houghtaling PL, Labinaz M, Kleiman NS. et al. Enhanced efficacy of eptifibatide administration in patients with acute coronary syndrome requiring in-hospital coronary artery bypass grafting. Circulation 2000; 102: 2952-8.
    CrossrefPubMedGoogle Scholar
  • 70 Dyke CM, Bhatia D, Lorenz TJ, Marso SP, Tardiff BE, Hogeboom C. et al. Immediate coronary artery bypass surgery after platelet inhibition with eptifibatide: results from PURSUIT. Platelet Glycoprotein IIb/IIIa in Unstable Angina: Receptor Suppression Using Integrelin Therapy. Ann Thorac Surg 2000; 70: 866-71.
    CrossrefPubMedGoogle Scholar
  • 71 Theroux P, Alexander Jr J, Pharand C, Barr E, Snapinn S, Ghannam AF. et al. Glycoprotein IIb/IIIa receptor blockade improves outcomes in diabetic patients presenting with unstable angina/non-ST-elevation myocar-dial infarction: results from the platelet receptor inhibition in ischemic syndrome management in patients limited by unstable signs and symptoms (PRISM-PLUS) study. Circulation 2000; 102: 2466-72.
    CrossrefPubMedGoogle Scholar
  • 72 Heeschen C, Hamm CW, Goldmann B, Deu A, Langenbrink L, White HD. Troponin concentrations for stratification of patients with acute coronary syndromes in relation to therapeutic efficacy of tirofiban. PRISM Study Investigators. Platelet Receptor Inhibition in Ischemic Syndrome Management. Lancet 1999; 354: 1757-62.
    CrossrefPubMedGoogle Scholar
  • 73 Barr E, Thornton AR, Sax FL. Benefit of tirofiban + heparin therapy in unstable angina/non-Q-wave myocardial infarction patients is observed regardless of interventional treatment strategy. Circulation 1998; 98: I-504a (abstr.).
    PubMedGoogle Scholar
  • 74 Bednar B, Cook JJ, Holahan MA, Cunningham ME, Jumes PA, Bednar RA. et al. Fibrinogen receptor antagonist-induced thrombocytopenia in chimpanzee and rhesus monkey associated with preexisting drug-dependent antibodies to platelet glycoprotein IIb/IIIa. Blood 1999; 94: 587-99.
    PubMedGoogle Scholar
  • 75 Skubas NJ, Despotis GJ, Vlasnic JJ, Moon MR. Preoperative use of enoxaparin and tirofiban: possible association with increased bleeding postbypass. Anesthesiology 1999; 91: 869-72.
    CrossrefPubMedGoogle Scholar
  • 76 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. Potential implications for the effect of c7E3 Fab treatment on acute thrombosis and “clinical restenosis”. J Clin Invest 1996; 98: 863-74.
    CrossrefPubMedGoogle Scholar
  • 77 Moliterno DJ, Califf RM, Aguirre FV, Anderson K, Sigmon KN, Weisman HF. et al. Effect of platelet glycoprotein IIb/IIIa integrin blockade on activated clotting time during percutaneous transluminal coronary angioplasty or directional atherectomy (the EPIC trial). Evaluation of c7E3 Fab in the Prevention of Ischemic Complications trial. Am J Cardiol 1995; 75: 559-62.
    CrossrefPubMedGoogle Scholar
  • 78 Dangas G, Marmur JD, King TE, De Leon J, Sharma SK, Vidhun R. et al. Effects of platelet glycoprotein IIb/IIIa inhibition with abciximab on thrombin generation and activity during percutaneous coronary intervention. Am Heart J 1999; 138: 49-54.
    CrossrefPubMedGoogle Scholar
  • 79 Ambrose JA, Hawkey M, Badimon JJ, Coppola J, Geagea J, Rentrop KP. et al. In vivo demonstration of an antithrombin effect of abciximab. Am J Cardiol 2000; 86: 150-2.
    CrossrefPubMedGoogle Scholar
  • 80 Barry OP, FitzGerald GA. Mechanisms of cellular activation by platelet microparticles. Thromb Haemost 1999; 82: 794-800.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 81 Coller BS. Platelets and thrombolytic therapy. N Engl J Med 1990; 322: 33-42.
    CrossrefPubMedGoogle Scholar
  • 82 Coller BS. Augmentation of thrombolysis with antiplatelet drugs. Overview. Coron Art Dis 1995; 6: 911-4.
    PubMedGoogle Scholar
  • 83 Campbell B, Chuhran CM, Lefer DJ, Lefer AM. Cardioprotective effects of abciximab (ReoPro) in an isolated perfused rat heart model of ischemia and reperfusion. Methods Find Exp Clin Pharmacol 1999; 21: 529-34.
    CrossrefPubMedGoogle Scholar
  • 84 Simoons ML, van den BM, Lincoff M, Harrington R, Van der WR, Vahanian A. et al. Minimal myocardial damage during coronary intervention is associated with impaired outcome. Eur Heart J 1999; 20: 1112-9.
    CrossrefPubMedGoogle Scholar
  • 85 Saucedo JF, Mehran R, Dangas G, Hong MK, Lansky A, Kent KM. et al. Long-term clinical events following creatine kinase – myocardial band isoenzyme elevation after successful coronary stenting. J Am Coll Cardiol 2000; 35: 1134-41.
    CrossrefPubMedGoogle Scholar
  • 86 Neumann FJ, Blasini R, Schmitt C, Alt E, Dirschinger J, Gawaz M. et al. Effect of glycoprotein IIb/IIIa receptor blockade on recovery of coronary flow and left ventricular function after the placement of coronary-artery stents in acute myocardial infarction. Circulation 1998; 98: 2695-701.
    CrossrefPubMedGoogle Scholar
  • 87 de Lemos JA, Antman EM, Gibson CM, McCabe CH, Giugliano RP, Murphy SA. et al. Abciximab improves both epicardial flow and myocar-dial reperfusion in ST-elevation myocardial infarction. Observations from the TIMI 14 trial. Circulation 2000; 101: 239-43.
    CrossrefPubMedGoogle Scholar
  • 88 Koch KC, vom DJ, Kleinhans E, Klues HG, Radke PW, Ninnemann S. et al. Influence of a platelet GPIIb/IIIa receptor antagonist on myocardial hypoperfusion during rotational atherectomy as assessed by myocardial Tc-99m sestamibi scintigraphy. J Am Coll Cardiol 1999; 33: 998-1004.
    CrossrefPubMedGoogle Scholar
  • 89 Ridker PM, Hennekens CH, Buring JE, Rifai N. C-reactive protein and other markers of inflammation in the prediction of cardiovascular disease in women. N Engl J Med 2000; 342: 836-43.
    CrossrefPubMedGoogle Scholar
  • 90 Mickelson JK, Kleiman NS, Lakkis NM, Chow TW, Hughes BS, Smith CW. Chimeric 7E3 Fab (ReoPro) decreases detectable CD11b on neutrophils from patients undergoing coronary angiplasty. Am J Cardiol 1999; 33: 97-106.
    CrossrefPubMedGoogle Scholar
  • 91 Neumann FJ, Zohlnhofer D, Fakhoury L, Ott I, Gawaz M, Schomig A. Effect of glycoprotein IIb/IIIa receptor blockade on platelet-leukocyte interaction and surface expression of the leukocyte integrin Mac-1 in acute myocardial infarction. J Am Coll Cardiol 1999; 34: 1420-6.
    CrossrefPubMedGoogle Scholar
  • 92 Henn V, Slupsky JR, Grafe M, Anagnostopoulos I, Forster R, MullerBerghaus G. et al. CD40 ligand on activated platelets triggers an inflammatory reaction of endothelial cells. Nature 1998; 391: 591-4.
    CrossrefPubMedGoogle Scholar
  • 93 Van Kooten C, Banchereau J. CD40-CD40 ligand. J Leukoc Biol 2000; 67: 2-17.
    CrossrefPubMedGoogle Scholar
  • 94 Tsakiris DA, Tschopl M, Wolf F, Labs KH, Jager KA, Marbet GA. Platelets and cytokines in concert with endothelial activation in patients with peripheral arterial occlusive disease. Blood Coagul Fibrinolysis 2000; 11: 165-73.
    CrossrefPubMedGoogle Scholar
  • 95 Aukrust P, Muller F, Ueland T, Berget T, Aaser E, Brunsvig A. et al. Enhanced levels of soluble and membrane-bound CD40 ligand in patients with unstable angina: possible reflection of T lymphocyte and platelet involvement in the pathogenesis of acute coronary syndromes. Circulation 1999; 100: 614-20.
    CrossrefPubMedGoogle Scholar
  • 96 Liuzzo G, Buffon A, Biasucci LM, Gallimore JR, Caligiuri G, Vitelli A. et al. Enhanced inflammatory response to coronary angioplasty in patients with severe unstable angina. Circulation 1998; 98: 2370-6.
    CrossrefPubMedGoogle Scholar
  • 97 Bennett JS, Chan C, Vilaire G, Mousa SA, DeGrado WF. Agonist-activated alphavbeta3 on platelets and lymphocytes binds to the matrix protein osteopontin. J Biol Chem 1997; 272: 8137-40.
    CrossrefPubMedGoogle Scholar
  • 98 Helluin O, Chan C, Vilaire G, Mousa S, DeGrado WF, Bennett JS. The activation state of alphavbeta3 regulates platelet and lymphocyte adhesion to intact and thrombin-cleaved osteopontin. J Biol Chem 2000; 275: 18337-43.
    CrossrefPubMedGoogle Scholar
  • 99 Baron JH, Moiseeva EP, de Bono DP, Abrams KR, Gershlick AH. Inhibition of vascular smooth muscle cell adhesion and migration by c7E3 fab (abciximab): a possible mechanism for influencing restenosis. Cardiovasc Res 2000; 48: 464-72.
    CrossrefPubMedGoogle Scholar
  • 100 Li Y, Spencer FA, Ball S, Becker RC. Inhibition of platelet-dependent prothrombinase activity and thrombin generation by glycoprotein IIb/IIIa receptor-directed antagonists: potential contributing mechanism of benefit in acute coronary syndromes. J Thromb Thrombolysis 2000; 10: 69-76.
    PubMedGoogle Scholar
  • 101 Kleiman NS, Tracy RP, Talley JD, Sigmon K, Joseph D, Topol EJ. et al. Inhibition of platelet aggregation with a glycoprotein IIb-IIIa antagonist does not prevent thrombin generation in patients undergoing thrombolysis for acute myocardial infarction. J Thromb Thrombolysis 2000; 9: 5-12.
    PubMedGoogle Scholar
  • 102 Furman M, Krueger L, Frelinger AI. Tirofiban, eptifibatide, but not abciximab, leukocyte-platelet interactions. Circulation 2000; 100: I-681a (abstr.).
    PubMedGoogle Scholar
  • 103 Coller BS. Monitoring platelet GPIIb/IIIa antagonist therapy. Circulation 1998; 97: 5-9.
    CrossrefPubMedGoogle Scholar
  • 104 Kottke-Marchant K, Powers JB, Brooks L, Kundu S, Christie DJ. The effect of antiplatelet drugs, heparin, and preanalytical variables on platelet function detected by the platelet function analyzer (PFA-100). Clin Appl Thromb Hemost 1999; 5: 122-30.
    CrossrefPubMedGoogle Scholar
  • 105 Poullis M. A quick simple method of determining platelet aggregability following glycoprotein IIb/IIIa receptor inhibitor administration. Cardiology 1999; 91: 156-60.
    CrossrefPubMedGoogle Scholar
  • 106 Kereiakes DJ, Mueller M, Howard W, Lacock P, Anderson LC, Broderick TM. et al. Efficacy of abciximab induced platelet blockade using a rapid point of care assay. J Thromb Thrombolysis 1999; 7: 265-76.
    CrossrefPubMedGoogle Scholar
  • 107 Coiffic A, Cazes E, Janvier G, Forestier F, Lanza F, Nurden A. et al. Inhibition of platelet aggregation by abciximab but not by aspirin can be detected by a new point-of-care test, the hemostatus. Thromb Res 1999; 95: 83-91.
    CrossrefPubMedGoogle Scholar
  • 108 Peter K, Kohler B, Straub A, Ruef J, Moser M, Nordt T. et al. Flow cyto-metric monitoring of glycoprotein IIb/IIIa blockade and platelet function in patients with acute myocardial infarction receiving reteplase, abciximab, and ticlopidine: continuous platelet inhibition by the combination of abciximab and ticlopidine. Circulation 2000; 102: 1490-6.
    CrossrefPubMedGoogle Scholar
  • 109 Smith JW, Steinhubl SR, Lincoff AM, Coleman J, Lee T, Hillman RS. et al. The rapid platelet function assay (RPFA): an automated and quantitative cartridge-based method. Circulation 1999; 99: 620-5.
    CrossrefPubMedGoogle Scholar
  • 110 Steinhubl SR, Talley D, Braden GA, Casterella PJ, Tcheng J, Moliterno DJ. et al. Point-of-care measured platelet inhibition correlates with a reduced risk of an adverse cardiac event following percutaneous coronary intervention. Results of the GOLD (Au-Assessing Ultegra) multicenter study. Circulation. (in Press).
    PubMedGoogle Scholar
  • 111 Moliterno DJ, White HD. Unstable angina: PARAGON, PURSUIT, PRISM, and PRISM-Plus. In: Lincoff AM, Topol EJ. editors. Glycoprotein IIb/IIIa Inhibitors in Cardiology. Humana Press; 1998: 67-89.
    Google Scholar
  • 112 Moliterno DJ. Patient-specific dosing of IIb/IIIa antagonists during acute coronary syndromes: rationale and design of the PARAGON B study. The PARAGON B International Steering Committee. Am Heart J 2000; 139: 563-6.
    CrossrefPubMedGoogle Scholar
  • 113 Brener SJ, Barr LA, Burchenal JE, Katz S, George BS, Jones AA. et al. Randomized, placebo-controlled trial of platelet glycoprotein IIb/IIIa blockade with primary angioplasty for acute myocardial infarction. ReoPro and Primary PTCA Organization and Randomized Trial (RAPPORT) Investigators. Circulation 1998; 98: 734-41.
    CrossrefPubMedGoogle Scholar
  • 114 Montalescot G, Barragan P, Wittenbeerg O. Abciximab associated with primary angioplasty and stenting in acute myocardial infarction: the ADMIRAL study. Circulation 1999; 100: I-87a (abstr.).
    CrossrefPubMedGoogle Scholar
  • 115 Antman EM, Giugliano RP, Gibson CM, McCabe CH, Coussement P, Kleiman NS. et al. Abciximab facilitates the rate and extent of thrombolysis: results of the thrombolysis in myocardial infarction (TIMI) 14 trial. The TIMI 14 Investigators. Circulation 1999; 99: 2720-32.
    CrossrefPubMedGoogle Scholar
  • 116 Antman EM, Gibson CM, de Lemos JA, Giugliano RP, McCabe CH, Coussement P. et al. Combination reperfusion therapy with abciximab and reduced dose reteplase: results from TIMI 14. Eur Heart J 2000; 21: 1944-53.
    CrossrefPubMedGoogle Scholar
  • 117 Trial of abciximab with and without low-dose reteplase for acute myocar-dial infarction.. Strategies for Patency Enhancement in the Emergency Department (SPEED) Group. Circulation 2000; 101: 2788-94.
    CrossrefPubMedGoogle Scholar
  • 118 Campbell KR, Ohman EM, Cantor W, Lincoff AM. The use of glycoprotein IIb/IIIa inhibitor therapy in acute ST-segment elevation myocardial infarction: current practice and future trends. Am J Cardiol 2000; 85: 32C-8.
    PubMedGoogle Scholar
  • 119 Herrmann HC, Moliterno DJ, Ohman EM, Stebbins AL, Bode C, Betriu A. et al. Facilitation of early percutaneous coronary intervention after reteplase with or without abciximab in acute myocardial infarction: results from the SPEED (GUSTO-4 Pilot) Trial. J Am Coll Cardiol 2000; 36: 1489-96.
    CrossrefPubMedGoogle Scholar
  • 120 Cohen M, Maritz F, Franco GG, Danchin N, Timerman A, Huber K. et al. The TETAMI Trial: The safety and efficacy of subcutaneous enoxaparin versus intravenous unfractionated heparin and of tirofiban versus placebo in the treatment of acute myocardial infarction for patients not thrombolyzed: Methods and design. J Thromb Thrombolysis 2000; 10: 241-6.
    CrossrefPubMedGoogle Scholar
  • 121 Tepe G, Schott U, Erley CM, Albes J, Claussen CD, Duda SH. Platelet glycoprotein IIb/IIIa receptor antagonist used in conjunction with thrombolysis for peripheral arterial thrombosis. Am J Roentgenol 1999; 172: 1343-6.
    CrossrefPubMedGoogle Scholar
  • 122 Abciximab in acute ischemic stroke: a randomized, double-blind, placebo-controlled, dose-escalation study.. The Abciximab in Ischemic Stroke Investigators. Stroke 2000; 31: 601-9.
    CrossrefPubMedGoogle Scholar
  • 123 Cheung RT, Ho DS. Fatal hemorrhagic transformation of acute cerebral infarction after the use of abciximab. Stroke 2000; 31: 2517-27.
    PubMedGoogle Scholar
  • 124 Wallace RC, Furlan AJ, Moliterno DJ, Stevens GH, Masaryk TJ, Perl J. Basilar artery rethrombosis: successful treatment with platelet glycoprotein IIB/IIIA receptor inhibitor. Am J Neuroradiol 1997; 18: 1257-60.
    PubMedGoogle Scholar
  • 125 Cecena FA, Hoelzinger DH, Miller JA, Abu-Shakra S. The platelet IIb/IIIa inhibitor abciximab as adjunctive therapy in carotid stenting of potential thrombotic lesions. J Intervent Cardiol 1999; 12: 355-62.
    CrossrefPubMedGoogle Scholar
  • 126 Kuker W, Friese S, Vogel W, Schmidt F, Weller M. Incomplete resolution of basilar artery occlusion after intra-arterial thrombolysis: abciximab and heparin prevent early rethrombosis. Cerebrovasc Dis 2000; 10: 484-6.
    CrossrefPubMedGoogle Scholar
  • 127 Tong FC, Cloft HJ, Joseph GJ, Samuels OB, Dion JE. Abciximab rescue in acute carotid stent thrombosis. Am J Neuroradiol 2000; 21: 1750-2.
    PubMedGoogle Scholar
  • 128 Schneiderman J, Morag B, Gerniak A, Rimon U, Varon D, Seligsohn U. et al. Abciximab in carotid stenting for postsurgical carotid restenosis: intermediate results. J Endovasc Ther 2000; 7: 263-72.
    CrossrefPubMedGoogle Scholar
  • 129 Cantor WJ, Leblanc K, Garvey B, Watson KR, Rasymas A, Strauss BH. Combined use of Orgaran and Reopro during coronary angioplasty in patients unable to receive heparin. Catheter Cardiovasc Interv 1999; 46: 352-5.
    CrossrefPubMedGoogle Scholar
  • 130 Walenga JM, Jeske WP, Wallis DE, Bakhos M, Lewis BE, Leya F. et al. Clinical experience with combined treatment of thrombin inhibitors and GPIIb/IIIa inhibitors in patients with HIT. Semin Thromb Hemost 1999; 25 (Suppl. 01) 77-81.
    PubMedGoogle Scholar
  • 131 Laubenthal FC, Grosch B, Szurawitzki G, Sabin GV. Heparin-induced thrombocytopenia type II with early aortocoronary bypass occlusion and stent thrombosis after PTCA of the RCA – treatment with lepirudin (Refludan) and abciximab (Reo pro) during recanalization of the RCA. Z Kardiol 1999; 88: 141-6.
    CrossrefPubMedGoogle Scholar
  • 132 Etheridge SP, Tani LY, Minich LL, Revenaugh JR. Platelet glycoprotein IIb/IIIa receptor blockade therapy for large coronary aneurysms and thrombi in Kawasaki disease. Cathet Cardiovasc Diagn 1998; 45: 264-8.
    CrossrefPubMedGoogle Scholar
  • 133 Varner JA, Nakada MT, Jordan RE, Coller BS. Inhibition of angiogenesis and tumor growth by murine 7E3, the parent antibody of c7E3 Fab (abciximab, ReoPro™). Angiogenesis 1999; 3: 53-60.
    CrossrefPubMedGoogle Scholar
  • 134 Amirkhosravi A, Amaya M, Siddiqui F, Biggerstaff JP, Meyer TV, Francis JL. Blockade of GPIIb/IIIa inhibits the release of vascular endothelial growth factor (VEGF) from tumor cell-activated platelets and experimental metastasis. Platelets 1999; 10: 285-92.
    CrossrefPubMedGoogle Scholar
  • 135 Karpatkin SE, Pearlstein C, Ambrogio C, Coller BS. Role of adhesive proteins in platelet tumor interaction in vitro and metastasis formation in vivo. J Clin Invest 1987; 81: 1012-9.
    PubMedGoogle Scholar
  • 136 Cohen SA, Trikha M, Mascelli MA. Potential future clinical applications for the GPIIb/IIIa antagonist, abciximab in thrombosis, vascular and onco-logical indications. Pathol Oncol Res 2000; 6: 163-74.
    CrossrefPubMedGoogle Scholar
  • 137 Gutheil JC, Campbell TN, Pierce PR, Watkins JD, Huse WD, Bodkin DJ. et al. Targeted antiangiogenic therapy for cancer using Vitaxin: a humanized monoclonal antibody to the integrin alphavbeta3. Clin Cancer Res 2000; 6: 3056-61.
    PubMedGoogle Scholar
  • 138 Kaul DK, Tsai HM, Liu XD, Nakada MT, Nagel RL, Coller BS. Monoclonal antibodies to alphaVbeta3 (7E3 and LM609) inhibit sickle red blood cell-endothelium interactions induced by platelet-activating factor. Blood 2000; 95: 368-74.
    PubMedGoogle Scholar
  • 139 Francis Jr RB. Platelets, coagulation, and fibrinolysis in sickle cell disease: their possible role in vascular occlusion. Blood Coagul Fibrinolysis 1991; 2: 341-53.
    CrossrefPubMedGoogle Scholar
  • 140 Rao AK, Sun L, Hiramatsu Y, Gorman III JH, Edmunds Jr LH. Glyco-protein IIb/IIIa receptor antagonist tirofiban inhibits thrombin generation during cardiopulmonary bypass in baboons. Thromb Haemost 1999; 82: 140-4.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 141 Yomo T, Serna DL, Powell LL, Wang D, Wilson SE, Ishimaru S. et al. Glycoprotein IIb/IIIa receptor inhibitor attenuates platelet aggregation induced by thromboxane A2 during in vitro nonpulsatile ventricular assist circulation. Artif Organs 2000; 24: 355-61.
    CrossrefPubMedGoogle Scholar
  • 142 Taylor FB, Coller BS, Chang ACK, Peer G, Jordan R, Engellener W. et al. 7E3 F(ab’)2, a monoclonal antibody to the platelet GPIIb/IIIa receptor, protects against microangiopathic hemolytic anemia and microvascular thrombotic renal failure in baboons treated with C4b binding protein and a sublethal infusion of Escherichia coli. Blood 1997; 89: 4078-84.
    PubMedGoogle Scholar
  • 143 O’Neill WW, Serruys P, Knudtson M, van Es GA, Timmis GC, van der Zwann C. et al. Long-term treatment with a platelet glycoprotein-receptor antagonist after percutaneous coronary revascularization. EXCITE Trial Investigators. Evaluation of Oral Xemilofiban in Controlling Thrombotic Events. N Engl J Med 2000; 342: 1316-24.
    CrossrefPubMedGoogle Scholar
  • 144 Cannon CP, McCabe CH, Wilcox RG, Langer A, Caspi A, Berink P. et al. Oral glycoprotein IIb/IIIa inhibition with orbofiban in patients with unstable coronary syndromes (OPUS-TIMI 16) trial. Circulation 2000; 102: 149-56.
    CrossrefPubMedGoogle Scholar
  • 145 Comparison of sibrafiban with aspirin for prevention of cardiovascular events after acute coronary syndromes: a randomised trial.. The SYMPHONY Investigators. Sibrafiban versus Aspirin to Yield Maximum Protection from Ischemic Heart Events Post-acute Coronary Syndromes. Lancet 2000; 355: 337-45.
    CrossrefPubMedGoogle Scholar
  • 146 Chew D, Bhatt DL, Sapp SK, Topol EJ. Increased mortality with oral glycoprotein IIb/IIIa antagonists. Circulation 2001; 103: 201-6.
    CrossrefPubMedGoogle Scholar
  • 147 Cox D, Smith R, Quinn M, Theroux P, Crean P, Fitzgerald DJ. Evidence of platelet activation during treatment with a GPIIb/IIIa antagonist in patients presenting with acute coronary syndromes. J Am Coll Cardiol 2000; 36: 1514-9.
    CrossrefPubMedGoogle Scholar
  • 148 Holmes MB, Sobel BE, Cannon CP, Schneider DJ. Increased platelet reactivity in patients given orbofiban after an acute coronary syndrome: an OPUS-TIMI 16 substudy. Orbofiban in Patients with Unstable Coronary Syndromes. Thrombolysis In Myocardial Infarction. Am J Cardiol 2000; 85: 491-3.
    CrossrefPubMedGoogle Scholar
  • 149 Adderley SR, Fitzgerald DJ. Glycoprotein IIb/IIIa antagonists induce apoptosis in rat cardiomyocytes by caspase-3 activation. J Biol Chem 2000; 275: 5760-6.
    CrossrefPubMedGoogle Scholar
  • 150 Schomig A, Kastrati A, Dirschinger J, Mehilli J, Schricke U, Pache J. et al. Coronary stenting plus platelet glycoprotein IIb/IIIa blockade compared with tissue plasminogen activator in acute myocardial infarction. Stent versus Thrombolysis for Occluded Coronary Arteries in Patients with Acute Myocardial Infarction Study Investigators. N Engl J Med 2000; 343: 385-91.
    CrossrefPubMedGoogle Scholar