Oral glycoprotein IIb/IIIa receptor inhibitors in patients with cardiovascular disease: Why were the results so unfavourable

European Heart Journal

Volumn 23, Issue 6, 2002, Pages 444-457

  Leebeek, F W G ^a   Boersma, E ^a   Cannon, C P ^b   Van De Werf, F J J ^c   Simoons, M L ^a  

^a ERASMUS MEDICAL CENTER   (Netherlands)

^b BRIGHAM AND WOMEN S HOSPITAL   (United States)

^c UNIVERSITY OF LEUVEN   (Belgium)

Author keywords

[No Author keywords available]

Indexed keywords

ABCIXIMAB; ACETYLSALICYLIC ACID; CHROMOFIBAN; EPTIFIBATIDE; FIBRINOGEN RECEPTOR ANTAGONIST; LEFRADAFIBAN; LOTRAFIBAN; N [(4 METHYLPHENYL)SULFONYL] 3 [[[5,6,7,8 TETRAHYDRO 4 OXO 5 [2 (4 PIPERIDINYL)ETHYL] 4H PYRAZOLO[1,5 A][1,4]DIAZEPIN 2 YL]CARBONYL]AMINO]ALANINE; N ETHYL N [4 (4 PIPERIDINYL)BUTYRYL]GLYCYLASPARTYL 3 CYCLOHEXYLALANINAMIDE; ORBOFIBAN; ROXIFIBAN; SIBRAFIBAN; TIROFIBAN; UNCLASSIFIED DRUG; XEMILOFIBAN;

BLEEDING; BRAIN HEMORRHAGE; CARDIOVASCULAR DISEASE; CLINICAL TRIAL; DOSE RESPONSE; DRUG BIOAVAILABILITY; DRUG EFFECT; DRUG EFFICACY; DRUG EXCRETION; DRUG HALF LIFE; DRUG INDUCED DISEASE; DRUG USE; HEART REINFARCTION; HUMAN; LONG TERM CARE; OUTCOMES RESEARCH; PRIORITY JOURNAL; REVIEW; SECONDARY PREVENTION; THROMBOCYTE AGGREGATION INHIBITION; THROMBOSIS; TRANSLUMINAL CORONARY ANGIOPLASTY;

ADMINISTRATION, ORAL; CARDIOVASCULAR DISEASES; CLINICAL TRIALS; HUMANS; PLATELET AGGREGATION INHIBITORS; PLATELET GLYCOPROTEIN GPIIB-IIIA COMPLEX;

EID: 0036522141     PISSN: 0195668X     EISSN: None     Source Type: Journal    
DOI: 10.1053/euhj.2001.2751     Document Type: Review

References (52)

1. Secondary prevention of vascular disease by prolonged anti-platelet treatment. Antiplatelet Trialists' Collaboration. Br Med J (Clin Res Ed) 1988; 30 (6618): 320-31.
2. Collaborative overview of randomised trials of antiplatelet therapy - I: Prevention of death, myocardial infarction, and stroke by prolonged antiplatelet therapy in various categories of patients. Antiplatelet Trialists' Collaboration. BMJ 1994; 308: 81-106.
3. A randomised, blinded, trial of clopidogrel versus aspirin in patients at risk of ischaemic events (CAPRIE). CAPRIE Steering Committee. Lancet 1996; 348: 1329-39.
4. Smith P, Arnesen H, Holme I. The effect of warfarin on mortality and reinfarction after myocardial infarction. N Engl J Med 1990; 323: 147-52.
5. Effect of long-term oral anticoagulant treatment on mortality and cardiovascular morbidity after myocardial infarction. Anticoagulants in the Secondary Prevention of Events in Coronary Thrombosis (ASPECT) Research Group. Lancet 1994; 343: 499-503.
6. Ronner E, Dykun Y, van den Brand MJ, van der Wieken LR, Simoons ML. Platelet glycoprotein IIB/IIIA receptor antagonists. An asset for treatment of unstable coronary syndromes and coronary intervention. Eur Heart J 1998; 19: 1608-16.
7. Kong DF, Califf RM, Miller DP et al. Clinical outcomes of therapeutic agents that block the platelet glycoprotein IIb/IIIa integrin ischemic heart disease. Circulation 1998; 98: 2829-35.
8. Use of 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.
9. Randomised placebo-controlled trial of abciximab before and during coronary intervention in refractory unstable angina: The CAPTURE Study. Lancet 1997; 349: 1429-35.
10. Platelet glycoprotein IIb/IIIa receptor blockade and low-dose heparin during percutaneous coronary revascularization. The EPILOG Investigators. N Engl J Med 1997; 336: 1689-96.
11. Randomised placebo-controlled and balloon-angioplasty-controlled trial to assess safety of coronary stenting with use of platelet glycoprotein-IIb/IIIa blockade. The EPISTENT Investigators. Evaluation of Platelet IIb/IIIa Inhibitor for Stenting. Lancet 1998; 352: 87-92.
12. 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: 1445-53.
13. Randomised placebo-controlled trial of effect of eptifibatide on complications of percutaneous coronary intervention: IMPACT-II. Integrilin to Minimize Platelet Aggregation and Coronary Thrombosis-II. Lancet 1997; 349: 1422-8.
14. Tcheng JE. The ESPRIT study: A randomized, Placebo-Controlled Trial of A Novel Dosing Regimen of Eptifibatide in Planned Coronary Stent Implantation. (in press)
15. 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: 734-41.
16. Neumann FJ, Kastrati A, Schmitt C et al. Effect of glycoprotein IIb/IIIa receptor blockade with abciximab on clinical and angiographic restenosis after the placement of coronary stents following acute myocardial infarction. J Am Coll Cardiol 2000; 35: 915-21.
17. 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.
18. Topol EJ. TARGET study: Do Tirofiban and Rheopro give similar efficacy trial. Circulation 2000; abstracts presented at the AHA, November 2000.
19. A comparison of aspirin plus tirofiban with aspirin plus heparin for unstable angina. Platelet Receptor Inhibition in Ischemic Syndrome Management (PRISM) Study Investigators. N Engl J Med 1998; 338: 1498-505.
20. Inhibition of platelet glycoprotein IIb/IIIa receptor with tirofiban in unstable angina and non-Q-wave myocardial infarction. Platelet Receptor Inhibition in Ischemic Syndrome Management in Patients Limited by Unstable Signs and Symptoms (PRISM-PLUS) Study Investigators. N Engl J Med 1998; 338: 1488-97.
21. 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.
22. 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.
23. O'Shea JC, Hafley GE, Greenberg S et al. Platelet glycoprotein IIb/IIIa integrin blockade with eptifibatide in coronary stent intervention: The ESPRIT Trial: A randomized controlled trial. JAMA 2001; 285: 2468-73.
24. Topol EJ, Byzova TV, Plow EF. Platelet GPIIb-IIIa blockers. Lancet 1999; 353: 227-31.
25. Verstraete M. Synthetic inhibitors of platelet glycoprotein IIb/IIIa in clinical development. Circulation 2000; 101: E76-E80.
26. O'Neill WW, Serruys P, Knudtson M 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.
27. Cannon CP, McCabe CH, Wilcox RG et al. Oral glycoprotein IIb/IIIa inhibition with orbofiban in patients with unstable coronary syndromes (OPUS-TIMI 16) trial. Circulation 2000; 102: 149-56.
28. 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.
29. Newby LK. A randomized comparison of sibrafiban, an oral glycoprotein (GP) IIb/IIIa receptor antagonist, with and without aspirin versus aspirin after acute coronary syndromes (ACS): Results of the second SYMPHONY trial. In: Kleiman NS, Califf RM. Results from Late-Breaking Clinical Trial Sessions at ACCIS 2000 and ACC 2000. J Am Coll Cardiol 2000; 36: 309-25.
30. Coller BS, Folts JD, Smith SR, Scudder LE, Jordan R. Abolition of in vivo platelet thrombus formation in primates with monoclonal antibodies to the platelet GPIIb/IIIa receptor. Correlation with bleeding time, platelet aggregation, and blockade of GPIIb/IIIa receptors. Circulation 1989; 80: 1766-74.
31. Steinbuhl SR, Kottke-Marchant K, Moliterno DJ 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.
32. Harrington RA, Armstrong PW, Graffagnino C et al. Dose-finding, safety, and tolerability study of an oral platelet glycoprotein IIb/IIIa inhibitor, lotrafiban, in patients with coronary or cerebral atherosclerotic disease. Circulation 2000; 102: 728-35.
33. Akkerhuis KM, Neuhaus KL, Wilcox RG et al. for the FROST investigators. Safety and preliminary efficacy of one month glycoprotein IIb/IIIa inhibition with lefradafiban in patients with acute coronary syndromes without ST-elevation: A phase II study. Eur Heart J 2000; 21: 2042-55.
34. Cannon CP, McCabe CH, Borzak S et al. Randomized trial of an oral platelet glycoprotein IIb/IIIa antagonist, sibrafiban in patients after an acute coronary syndrome: Results of the TIMI 12 trial. Thrombolysis in myocardial infarction. Circulation 1998; 97: 340-9.
35. Kereiakes DJ, Kleiman NS, Ferguson JJ et al. Pharmacodynamic efficacy, clinical safety, and outcomes after prolonged platelet Glycoprotein IIb/IIIa receptor blockade with oral xemilofiban: Results of a multicenter, placebo-controlled, randomized trial. Circulation 1998; 98: 1268-78.
36. Giugliano RP, McCabe CH, Sequiera RF et al. First report of an intravenous and oral glycoprotein IIb/IIIa inhibitor (RPR 109891) in patients with recent acute coronary syndromes: Results of the TIMI 15A and 15B trials. Am Heart J 2000; 140: 81-93.
37. Peter K, Schwarz M, Ylanne J et al. Induction of fibrinogen binding and platelet aggregation as a potential intrinsic property of various glycoprotein IIb/IIIa inhibitors. Blood 1998; 92: 3240-9.
38. 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. Orobifiban in Patients with Unstable coronary syndromes. Thrombolysis in myocardial infarction. Am J Cardiol 2000; 85: 491-3, A10.
39. Cox D, Smith R, Quinn M et al. Evidence of platelet activation during treatment with a GPIIa/IIIb antagonist in patients presenting acute coronary syndromes. J Am Coll Cardiol 2000; 36: 1514-19.
40. Pratico D, Murphy NP, Fitzgerald DJ. Interaction of a thrombin inhibitor and a platelet GPIIb/IIIa antagonist in vivo: Evidence that thrombin mediates platelet aggregation and subsequent thromboxane A2 formation during coronary thrombolysis. J Pharmacol Exp Ther 1997; 281: 1178-85.
41. 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.
42. Dangas G, Marmur JD, King TE 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.
43. Phillips DR, Teng W, Arfsten A 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 calcium in plasma anticoagulated with citrate. Circulation 1997; 96: 1488-94.
44. Rebello SS, Huang J, Faul JD, Lucchesi BR. Role of extracellular ionized calcium in the in vitro assessment of GPIIb/IIIa receptor antagonists. J Thromb Thrombolysis 2000; 9: 23-8.
45. Harrington RA, Kleiman NS, Granger CB, Ohman EM, Berkowitz SD. Relation between inhibition of platelet aggregation and clinical outcomes. Am Heart J 1998; 136: S43-S50.
46. Coller BS, Land D, Scudder LE. Rapid and simple platelet function assay to assess glycoprotein IIB/IIIa receptor blockade. Circulation 1997; 95: 860-7.
47. Smith JW, Steinhubl SR, Lincoff AM et al. Rapid platelet-function assay: An automated and quantitative cartridge-based method. Circulation 1999; 99: 620-5.
48. Storey RF, May JA, Wilcox RG, Heptinstall S. A whole blood assay of inhibition of platelet aggregation by glycoprotein IIb/IIIa antagonists: Comparison with other aggregation methodologies. Thromb Haemost 1999; 82: 1307-11.
49. Weiss EJ, Bray PF, Tayback M et al. A polymorphism of a platelet glycoprotein receptor as an inherited risk factor for coronary thrombosis. N Engl J Med 1996; 334: 1090-4.
50. Ridker PM, Hennekens CH, Schmitz C, Stampfer MJ, Lindpaintner K. PIA1/A2 polymorphism of platelet glycoprotein IIIa and risks of myocardial infarction, stroke and venous thrombosis. Lancet 1997; 349: 385-8.b
51. Walter DH, Schachinger V, Elsner M, Dimmeler S, Zeiher AM. Platelet glycoprotein IIIa polymorphisms and risk of coronary stent thrombosis. Lancet 1997; 350: 1217-19.
52. Chew DP, Bhatt DL, Sapp S, Topol EJ. Increased mortality with oral platelet glycoprotein IIb/IIIa antagonists. A meta-analysis of phase III multicenter randomized trials. Circulation 2001; 103: 201-6.