Official reprint from UpToDate®
www.uptodate.com ©2017 UpToDate, Inc. and/or its affiliates. All Rights Reserved.

Early trials of platelet glycoprotein IIb/IIIa receptor inhibitors in coronary heart disease

Richard C Becker, MD
Section Editor
Christopher P Cannon, MD
Deputy Editor
Gordon M Saperia, MD, FACC


Platelets play a pivotal role in normal hemostasis, maintaining vascular integrity and preventing continued blood loss after vascular injury. However, they also contribute directly to pathologic vascular thrombosis. This relationship constitutes the rationale for the use of antiplatelet agents in the treatment of coronary heart disease (CHD). (See "The role of platelets in coronary heart disease".)

Three intravenous platelet glycoprotein (GP) IIb/IIIa inhibitors have been studied extensively and are available for clinical use: abciximab, tirofiban, and eptifibatide. Abciximab is a monoclonal antibody directed against the receptor, while tirofiban and eptifibatide are high affinity non-antibody receptor inhibitors.

Antiplatelet therapy with intravenous GP IIb/IIIa inhibitors has been evaluated in patients with acute coronary syndrome (ACS) and in those undergoing intracoronary stent implantation. Dual oral antiplatelet therapy with aspirin and a platelet P2Y12 receptor blocker has decreased the role of GP IIb/IIIa therapy in these settings, although it continues to be important in some subgroups of patients with CHD.

This topic summarizes the early trials of GP IIb/IIIa inhibitors performed before the routine use of intracoronary stents in patients undergoing percutaneous coronary intervention and P2Y12 receptor blocker therapy in patients with ACS or those undergoing stenting. These early trials collectively formed the basis of a high-intensity, platelet-directed approach (in addition to aspirin) to pharmacotherapy for patients at high risk for myocardial infarction (MI), recurring MI, intra-coronary thromboembolism, and, with the increasing deployment of stents in routine clinical practice, acute stent thrombosis.

The role of platelet GP IIb/IIIa inhibitors in patients who receive currently recommended treatment with dual (oral) antiplatelet therapy is discussed elsewhere. (See "Antiplatelet agents in acute non-ST elevation acute coronary syndromes" and "Long-term antiplatelet therapy after coronary artery stenting in stable patients" and "Antiplatelet agents in acute ST elevation myocardial infarction".)

To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information on subscription options, click below on the option that best describes you:

Subscribers log in here

Literature review current through: Nov 2017. | This topic last updated: Oct 02, 2017.
The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2017 UpToDate, Inc.
  1. Plow EF, Ginsberg MH. Cellular adhesion: GPIIb-IIIa as a prototypic adhesion receptor. Prog Hemost Thromb 1989; 9:117.
  2. 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.
  3. Topol EJ, Califf RM, Weisman HF, et al. Randomised trial of coronary intervention with antibody against platelet IIb/IIIa integrin for reduction of clinical restenosis: results at six months. The EPIC Investigators. Lancet 1994; 343:881.
  4. Topol EJ, Ferguson JJ, Weisman HF, et al. Long-term protection from myocardial ischemic events in a randomized trial of brief integrin beta3 blockade with percutaneous coronary intervention. EPIC Investigator Group. Evaluation of Platelet IIb/IIIa Inhibition for Prevention of Ischemic Complication. JAMA 1997; 278:479.
  5. EPILOG Investigators. Platelet glycoprotein IIb/IIIa receptor blockade and low-dose heparin during percutaneous coronary revascularization. N Engl J Med 1997; 336:1689.
  6. Lincoff AM, Tcheng JE, Califf RM, et al. Sustained suppression of ischemic complications of coronary intervention by platelet GP IIb/IIIa blockade with abciximab: one-year outcome in the EPILOG trial. Evaluation in PTCA to Improve Long-term Outcome with abciximab GP IIb/IIIa blockade. Circulation 1999; 99:1951.
  7. Brener SJ, Barr LA, Burchenal JE, 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.
  8. Simoons ML, de Boer MJ, van den Brand MJ, et al. Randomized trial of a GPIIb/IIIa platelet receptor blocker in refractory unstable angina. European Cooperative Study Group. Circulation 1994; 89:596.
  9. Randomised placebo-controlled trial of abciximab before and during coronary intervention in refractory unstable angina: the CAPTURE Study. Lancet 1997; 349:1429.
  10. van den Brand M, Laarman GJ, Steg PG, et al. Assessment of coronary angiograms prior to and after treatment with abciximab, and the outcome of angioplasty in refractory unstable angina patients. Angiographic results from the CAPTURE trial. Eur Heart J 1999; 20:1572.
  11. Klootwijk P, Meij S, Melkert R, et al. Reduction of recurrent ischemia with abciximab during continuous ECG-ischemia monitoring in patients with unstable angina refractory to standard treatment (CAPTURE). Circulation 1998; 98:1358.
  12. Hamm CW, Heeschen C, Goldmann B, 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.
  13. Heeschen C, Dimmeler S, Hamm CW, et al. Soluble CD40 ligand in acute coronary syndromes. N Engl J Med 2003; 348:1104.
  14. Bhatt DL, Lincoff AM, Califf RM, et al. The benefit of abciximab in percutaneous coronary revascularization is not device-specific. Am J Cardiol 2000; 85:1060.
  15. Montalescot G, Barragan P, Wittenberg O, et al. Platelet glycoprotein IIb/IIIa inhibition with coronary stenting for acute myocardial infarction. N Engl J Med 2001; 344:1895.
  16. Admiral Investigators. Three-year duration of benefit from abciximab in patients receiving stents for acute myocardial infarction in the randomized double-blind ADMIRAL study. Eur Heart J 2005; 26:2520.
  17. Neumann FJ, Kastrati A, Schmitt C, 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.
  18. Stone GW, Grines CL, Cox DA, et al. Comparison of angioplasty with stenting, with or without abciximab, in acute myocardial infarction. N Engl J Med 2002; 346:957.
  19. Antoniucci D, Rodriguez A, Hempel A, et al. A randomized trial comparing primary infarct artery stenting with or without abciximab in acute myocardial infarction. J Am Coll Cardiol 2003; 42:1879.
  20. De Luca G, Suryapranata H, Stone GW, et al. Abciximab as adjunctive therapy to reperfusion in acute ST-segment elevation myocardial infarction: a meta-analysis of randomized trials. JAMA 2005; 293:1759.
  21. EPISTENT Investigators. Randomised placebo-controlled and balloon-angioplasty-controlled trial to assess safety of coronary stenting with use of platelet glycoprotein-IIb/IIIa blockade. Lancet 1998; 352:87.
  22. Lincoff AM, Califf RM, Moliterno DJ, et al. Complementary clinical benefits of coronary-artery stenting and blockade of platelet glycoprotein IIb/IIIa receptors. Evaluation of Platelet IIb/IIIa Inhibition in Stenting Investigators. N Engl J Med 1999; 341:319.
  23. Kastrati A, Mehilli J, Schühlen H, et al. A clinical trial of abciximab in elective percutaneous coronary intervention after pretreatment with clopidogrel. N Engl J Med 2004; 350:232.
  24. Simoons ML, GUSTO IV-ACS Investigators. Effect of glycoprotein IIb/IIIa receptor blocker abciximab on outcome in patients with acute coronary syndromes without early coronary revascularisation: the GUSTO IV-ACS randomised trial. Lancet 2001; 357:1915.
  25. Ottervanger JP, Armstrong P, Barnathan ES, et al. Long-term results after the glycoprotein IIb/IIIa inhibitor abciximab in unstable angina: one-year survival in the GUSTO IV-ACS (Global Use of Strategies To Open Occluded Coronary Arteries IV--Acute Coronary Syndrome) Trial. Circulation 2003; 107:437.
  26. Kereiakes DJ, Kleiman NS, Ambrose J, 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.
  27. 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. The RESTORE Investigators. Randomized Efficacy Study of Tirofiban for Outcomes and REstenosis. Circulation 1997; 96:1445.
  28. Heeschen C, Hamm CW, Goldmann B, et al. 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.
  29. Platelet Receptor Inhibition in Ischemic Syndrome Management in Patients Limited by Unstable Signs and Symptoms (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.
  30. Valgimigli M, Percoco G, Barbieri D, et al. The additive value of tirofiban administered with the high-dose bolus in the prevention of ischemic complications during high-risk coronary angioplasty: the ADVANCE Trial. J Am Coll Cardiol 2004; 44:14.
  31. Cohen M, Gensini GF, Maritz F, et al. The safety and efficacy of subcutaneous enoxaparin versus intravenous unfractionated heparin and tirofiban versus placebo in the treatment of acute ST-segment elevation myocardial infarction patients ineligible for reperfusion (TETAMI): a randomized trial. J Am Coll Cardiol 2003; 42:1348.
  32. Platelet Receptor Inhibition in Ischemic Syndrome Management (PRISM) Study Investigators. A comparison of aspirin plus tirofiban with aspirin plus heparin for unstable angina. N Engl J Med 1998; 338:1498.
  33. Lee DP, Herity NA, Hiatt BL, et al. Adjunctive platelet glycoprotein IIb/IIIa receptor inhibition with tirofiban before primary angioplasty improves angiographic outcomes: results of the TIrofiban Given in the Emergency Room before Primary Angioplasty (TIGER-PA) pilot trial. Circulation 2003; 107:1497.
  34. van 't Hof AW, Ernst N, de Boer MJ, et al. Facilitation of primary coronary angioplasty by early start of a glycoprotein 2b/3a inhibitor: results of the ongoing tirofiban in myocardial infarction evaluation (On-TIME) trial. Eur Heart J 2004; 25:837.
  35. Ernst NM, Suryapranata H, Miedema K, et al. Achieved platelet aggregation inhibition after different antiplatelet regimens during percutaneous coronary intervention for ST-segment elevation myocardial infarction. J Am Coll Cardiol 2004; 44:1187.
  36. Van't Hof AW, Ten Berg J, Heestermans T, et al. Prehospital initiation of tirofiban in patients with ST-elevation myocardial infarction undergoing primary angioplasty (On-TIME 2): a multicentre, double-blind, randomised controlled trial. Lancet 2008; 372:537.
  37. ten Berg JM, van 't Hof AW, Dill T, et al. Effect of early, pre-hospital initiation of high bolus dose tirofiban in patients with ST-segment elevation myocardial infarction on short- and long-term clinical outcome. J Am Coll Cardiol 2010; 55:2446.
  38. Phillips DR, Scarborough RM. Clinical pharmacology of eptifibatide. Am J Cardiol 1997; 80:11B.
  39. Harrington RA, Kleiman NS, Kottke-Marchant K, et al. 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.
  40. Randomised placebo-controlled trial of effect of eptifibatide on complications of percutaneous coronary intervention: IMPACT-II. Integrilin to Minimise Platelet Aggregation and Coronary Thrombosis-II. Lancet 1997; 349:1422.
  41. Platelet Glycoprotein IIb/IIIa in Unstable Angina: Receptor Suppression Using Integrilin Therapy (PURSUIT) Trial Investigators. Inhibition of platelet glycoprotein IIb/IIIa with eptifibatide in patients with acute coronary syndromes. N Engl J Med 1998; 339:436.
  42. Kleiman NS, Lincoff AM, Flaker GC, et al. Early percutaneous coronary intervention, platelet inhibition with eptifibatide, and clinical outcomes in patients with acute coronary syndromes. PURSUIT Investigators. Circulation 2000; 101:751.
  43. ESPRIT Investigators. Enhanced Suppression of the Platelet IIb/IIIa Receptor with Integrilin Therapy. Novel dosing regimen of eptifibatide in planned coronary stent implantation (ESPRIT): a randomised, placebo-controlled trial. Lancet 2000; 356:2037.
  44. Sabatine MS, Jang IK. The use of glycoprotein IIb/IIIa inhibitors in patients with coronary artery disease. Am J Med 2000; 109:224.
  45. Memon MA, Blankenship JC, Wood GC, et al. 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.
  46. Tcheng JE, Kereiakes DJ, Lincoff AM, et al. Abciximab readministration: results of the ReoPro Readministration Registry. Circulation 2001; 104:870.
  47. Madan M, Kereiakes DJ, Hermiller JB, et al. Efficacy of abciximab readministration in coronary intervention. Am J Cardiol 2000; 85:435.
  48. Brown DL, Fann CS, Chang CJ. Meta-analysis of effectiveness and safety of abciximab versus eptifibatide or tirofiban in percutaneous coronary intervention. Am J Cardiol 2001; 87:537.
  49. Batchelor WB, Tolleson TR, Huang Y, et al. Randomized COMparison of platelet inhibition with abciximab, tiRofiban and eptifibatide during percutaneous coronary intervention in acute coronary syndromes: the COMPARE trial. Comparison Of Measurements of Platelet aggregation with Aggrastat, Reopro, and Eptifibatide. Circulation 2002; 106:1470.
  50. Kabbani SS, Aggarwal A, Terrien EF, et al. Suboptimal early inhibition of platelets by treatment with tirofiban and implications for coronary interventions. Am J Cardiol 2002; 89:647.
  51. Topol EJ, Moliterno DJ, Herrmann HC, et al. Comparison of two platelet glycoprotein IIb/IIIa inhibitors, tirofiban and abciximab, for the prevention of ischemic events with percutaneous coronary revascularization. N Engl J Med 2001; 344:1888.
  52. Roffi M, Moliterno DJ, Meier B, et al. Impact of different platelet glycoprotein IIb/IIIa receptor inhibitors among diabetic patients undergoing percutaneous coronary intervention: : Do Tirofiban and ReoPro Give Similar Efficacy Outcomes Trial (TARGET) 1-year follow-up. Circulation 2002; 105:2730.
  53. Moliterno DJ, Yakubov SJ, DiBattiste PM, et al. Outcomes at 6 months for the direct comparison of tirofiban and abciximab during percutaneous coronary revascularisation with stent placement: the TARGET follow-up study. Lancet 2002; 360:355.
  54. Mukherjee D, Topol EJ, Bertrand ME, et al. Mortality at 1 year for the direct comparison of tirofiban and abciximab during percutaneous coronary revascularization: do tirofiban and ReoPro give similar efficacy outcomes at trial 1-year follow-up. Eur Heart J 2005; 26:2524.
  55. Steinhubl SR, Talley JD, Braden GA, et al. Point-of-care measured platelet inhibition correlates with a reduced risk of an adverse cardiac event after percutaneous coronary intervention: results of the GOLD (AU-Assessing Ultegra) multicenter study. Circulation 2001; 103:2572.
  56. Ohman EM, Kleiman NS, Gacioch G, et al. Combined accelerated tissue-plasminogen activator and platelet glycoprotein IIb/IIIa integrin receptor blockade with Integrilin in acute myocardial infarction. Results of a randomized, placebo-controlled, dose-ranging trial. IMPACT-AMI Investigators. Circulation 1997; 95:846.
  57. Antman EM, Giugliano RP, Gibson CM, 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.
  58. de Lemos JA, Antman EM, Gibson CM, et al. Abciximab improves both epicardial flow and myocardial reperfusion in ST-elevation myocardial infarction. Observations from the TIMI 14 trial. Circulation 2000; 101:239.
  59. Gibson CM, de Lemos JA, Murphy SA, et al. Combination therapy with abciximab reduces angiographically evident thrombus in acute myocardial infarction: a TIMI 14 substudy. Circulation 2001; 103:2550.
  60. Antman EM, Gibson CM, de Lemos JA, et al. Combination reperfusion therapy with abciximab and reduced dose reteplase: results from TIMI 14. The Thrombolysis in Myocardial Infarction (TIMI) 14 Investigators. Eur Heart J 2000; 21:1944.
  61. Trial of abciximab with and without low-dose reteplase for acute myocardial infarction. Strategies for Patency Enhancement in the Emergency Department (SPEED) Group. Circulation 2000; 101:2788.
  62. Brener SJ, Zeymer U, Adgey AA, et al. Eptifibatide and low-dose tissue plasminogen activator in acute myocardial infarction: the integrilin and low-dose thrombolysis in acute myocardial infarction (INTRO AMI) trial. J Am Coll Cardiol 2002; 39:377.
  63. Antman EM, Louwerenburg HW, Baars HF, et al. Enoxaparin as adjunctive antithrombin therapy for ST-elevation myocardial infarction: results of the ENTIRE-Thrombolysis in Myocardial Infarction (TIMI) 23 Trial. Circulation 2002; 105:1642.
  64. Giugliano RP, Roe MT, Harrington RA, et al. Combination reperfusion therapy with eptifibatide and reduced-dose tenecteplase for ST-elevation myocardial infarction: results of the integrilin and tenecteplase in acute myocardial infarction (INTEGRITI) Phase II Angiographic Trial. J Am Coll Cardiol 2003; 41:1251.