Glycoprotein IIb/IIIa Receptor Inhibitors in Percutaneous Coronary Intervention and Acute Coronary Syndrome

Abstract

Spanish

French

OBJECTIVE:

To review the contemporary role of the glycoprotein (GYP) IIb/IIIa receptor inhibitors abciximab, eptifibatide, and tirofiban in patients undergoing percutaneous coronary intervention (PCI) and those with an acute coronary syndrome (ACS), and to provide an algorithm based on currently available evidence for specific agents.

DATA SOURCES:

Primary articles were identified by a MEDLINE search (1966–January 2003); references cited in these articles provided additional resources.

STUDY SELECTION AND DATA EXTRACTION:

All of the articles identified from data sources were considered for relevant information; this article primarily addresses large, controlled or comparative studies, and meta-analyses.

DATA SYNTHESIS:

The role of GYP IIb/IIIa inhibitors in patients undergoing PCI and those with ACS has progressed markedly. To date, abciximab has the most robust data in patients undergoing PCI, particularly high-risk individuals. In PCI patients with lower risk (e.g., elective stenting), eptifibatide is a reasonable first-line option. Data do not support tirofiban for routine use in patients undergoing PCI. For individuals with signs and symptoms of ACS, specifically unstable angina or non–ST-segment elevation myocardial infarction (MI), eptifibatide or tirofiban is recommended in high-risk patients when a conservative approach is used (PCI is not planned). Abciximab is not recommended in this situation. In patients with ST-segment elevation MI (STEMI), abciximab is the only GYP IIb/IIIa inhibitor evaluated in large, well-designed investigations. For medical management in combination with a fibrinolytic agent, the role of abciximab remains unclear. For patients undergoing primary PCI for the management of STEMI, the available evidence supports the use of abciximab, albeit further investigation is warranted.

CONCLUSIONS:

The role of GYP IIb/IIIa inhibitors in clinical cardiology continues to evolve. Choice of the agent depends on situation of use, patient-specific characteristics and risk stratification, and, in the case of ACS, chosen management strategy (medical management or intervention).

Keywords

abciximab acute coronary syndrome eptifibatide glycoprotein IIb/IIIa receptor inhibitors percutaneous coronary intervention tirofiban

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References

Coller

. Monitoring platelet GP IIb/IIIa antagonist therapy. Circulation 1997; 96: 3828–32.

Chew

Moliterno

. A critical appraisal of platelet glycoprotein IIb/IIIa inhibition. J Am Coll Cardiol 2000; 36: 2028–35.

Topol

Moliterno

Herrmann

Powers

Cohen

, Comparison of two platelet glycoprotein IIb/IIIa inhibitors, tirofiban and abciximab, for the preventive ischemic events with percutaneous coronary revascularization. N Engl J Med 2001; 344: 1888–94.

Tcheng

Kereiakes

Lincoff

George

Kleiman

Sane

, Abciximab readministration: results of the ReoPro Readministration Registry. Circulation 2001; 104: 870–5.

Package insert. ReoPro (abciximab). Indianapolis: Eli Lilly, May 2001.

Package insert. Integrilin (eptifibatide). Cambridge, MA: Millennium Pharmaceuticals. May 2001.

Package insert. Aggrastat (tirofiban). Whitehouse Station, NJ: Merck and Company, May 2002.

Willerson

Golino

Eidt

Campbell

Buja

. Specific platelet mediators and unstable coronary artery lesions: experimental evidence and potential clinical implications. Circulation 1989; 80: 198–205.

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.

10.

Topol

Califf

Weisman

Ellis

Tcheng

Worley

, Randomised 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.

11.

Topol

Lincoff

Kereiakes

Kleiman

Cohen

Ferguson

, Multi- year follow-up of abciximab therapy in three randomized, placebo-controlled trials of percutaneous coronary revascularization. Am J Med 2002; 113: 1–6.

12.

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.

13.

Lincoff

Tcheng

Califf

Kelley

Timmis

Kleiman

, Sustained suppression of ischemic complications of coronary intervention by platelet GP IIb/IIIa blockade with abciximab: one-year outcome in the EPILOG trial. Circulation 1999; 99: 1951–8.

14.

Randomised placebo-controlled trial of abciximab before and during coronary intervention in refractory unstable angina: the CAPTURE study. The CAPTURE Investigators. Lancet 1997; 349: 1429–35.

15.

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. Lancet 1998; 352: 87–92.

16.

Topol

Mark

Lincoff

Cohen

Burton

Kleiman

, 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.

17.

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 REstonis. Circulation 1997; 96: 1445–53.

18.

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. The IMPACT-II Investigators. Lancet 1997; 349: 1422–8.

19.

Novel dosing regimen of eptifibatide in planned coronary stent implantation (ESPRIT): a randomised, placebo-controlled trial. The ESPRIT Investigators. Lancet 2000; 356: 2037–44.

20.

Rao

Pratt

Berke

Jaffe

Ockene

Schrieber

, 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.

21.

Lincoff

Califf

Moliterno

Ellis

Ducas

Kramer

, Complementary clinical benefits of coronary-artery stenting and blockade of platelet glycoprotein IIb/IIIa receptors. N Engl J Med 1999; 341: 319–27.

22.

Kabbani

Aggarwal

Terrien

DiBattiste

Sobel

Schneider

. Suboptimal early inhibition of platelets by treatment with tirofiban and implications for coronary interventions. Am J Cardiol 2002; 89: 647–50.

23.

Moliterno

Yakubov

DiBattiste

Herrmann

Stone

Macaya

, 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: 355–60.

24.

Stone

Moliterno

Bertrand

Neumann

Herrmann

Powers

, Impact of clinical syndrome acuity on the differential response to two glycoprotein IIb/IIIa inhibitors in patients undergoing coronary stenting: the TARGET trial (abstract). J Am Coll Cardiol 2002; 39 (suppl A): 22A.

25.

O'Shea

Buller

Cantor

Chandler

Cohen

, Long-term efficacy of platelet glycoprotein IIb/IIIa integrin blockade with eptifibatide in coronary stent intervention. JAMA 2002; 287: 618–21.

26.

Phillips

Teng

Arfsten

Nannizzi-Alaimo

White

Longhurst

, Effect of Ca2+ on GP IIb-IIIa interactions with integrilin: enhanced 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: 1488–94.

27.

Tcheng

Kereiakes

Kleiman

Talley

Wang

Weisman

, Pharmacodynamics of chimeric glycoprotein IIb/IIIa integrin antiplatelet antibody Fab 7E3 in high risk angioplasty. Circulation 1994; 90: 1757–64.

28.

Labinaz

Madan

O'Shea

Kilaru

Chin

Pieper

, Comparison of one-year outcomes following coronary artery stenting in diabetic versus nondiabetic patients (from the Enhanced Suppression of the Platelet IIb/IIIa Receptor With Integrilin Therapy [ESPRIT] Trial). Am J Cardiol 2002; 90: 585–90.

29.

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.

30.

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.

31.

Inhibition of the platelet glycoprotein IIb/IIIa receptor with tirofiban in unstable angina and non–Q-wave 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.

32.

Inhibition of the 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. [erratum N Engl J Med 1998; 339:415]

33.

Simoons

. 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: 1915–24.

34.

Randomized, placebo-controlled trial of titrated intravenous lamifiban for acute coronary syndromes. Circulation 2002; 105: 316–21.

35.

Cannon

Weintraub

Demopoulos

Vicari

Frey

Lakkis

, Comparison of early invasive and conservative strategies in patients with unstable coronary syndromes treated with the glycoprotein IIb/IIIa inhibitor tirofiban. N Engl J Med 2001; 344: 1879–87.

36.

Braunwald

Antman

Beasley

Califf

Cheitlin

Hochman

, ACC/AHA guideline update for the management of patients with unstable angina and non–ST-segment elevation myocardial infarction: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on the Management of Patients With Unstable Angina). 2002. www.acc.org/clinical/guidelines/unstable/unstable.pdf (accessed 2003 Jan 25).

37.

Boersma

Harrington

Moliterno

White

Simoons

. Platelet glycoprotein IIb/IIIa inhibitors in acute coronary syndromes: a meta-analysis of all major randomised clinical trials. Lancet 2002; 359: 189–98.

38.

Ottervanger

Armstrong

Barnathan

Boersma

Cooper

Ohman

, Long-term results after the glycoprotein IIb/IIIa inhibitor abciximab in unstable angina: one-year survival in the GUSTO IV-ACS. Circulation 2003; 107: 437–42.

39.

Invasive compared with non-invasive treatment in unstable coronary-artery disease: FRISC II prospective randomised multicentre study. FRagmin and Fast Revascularisation during InStability in Coronary artery disease Investigators. Lancet 1999; 354: 708–15.

40.

Wallentin

Lagerqvist

Husted

Kontny

Ståhle

Swahn

. Outcome at 1 year after an invasive compared with a non-invasive strategy in unstable coronary-artery disease: the FRISC II invasive randomised trial. Lancet 2000; 356: 9–16.

41.

Fox

Poole-Wilson

Henderson

Clayton

Chamberlain

Shaw

, Interventional versus conservative treatment for patients with unstable angina or non–ST-elevation myocardial infarction: the British Heart Foundation RITA 3 randomised trial. Lancet 2002; 360: 743–51.

42.

Kleiman

Ohman

Califf

George

Kereiakes

Aguirre

F V

, Profound inhibition of platelet aggregation with monoclonal antibody 7E3 Fab after thrombolytic therapy. J Am Coll Cardiol 1993; 22: 381–9.

43.

Ohman

Kleiman

Gacioch

Worley

Navetta

Talley

JSD

, Combined accelerated tissue-plasminogen activator and platelet glycoprotein IIb/IIIa integrin receptor blockade with integrilin in acute myocardial infarction. Circulation 1997; 95: 846–54.

44.

Combining thrombolysis with the platelet glycoprotein IIb/IIIa inhibitor lamifiban: results of the Platelet Aggregation Receptor Antagonist Dose Investigation and Reperfusion Gain in Myocardial Infarction (PARADIGM) trial. J Am Coll Cardiol 1998; 32: 2003–10.

45.

van der Merkhof

LFM

Zijlstra

Olsson

Grip

Veen

Bar

, Abciximab in the treatment of acute myocardial infarction eligible for primary percutaneous transluminal coronary angioplasty: results of the Glycoprotein Receptor Antagonist Patency Evaluation (GRAPE) pilot study. J Am Coll Cardiol 1999; 33: 1528–32.

46.

Antman

Giugliano

Gibson

McCabe

Coussement

Kleiman

, Abciximab facilitates the rate and extent of thrombolysis: results of the thrombolysis in myocardial infarction-14 (TIMI-14) trial. Circulation 1999; 99: 2720–32.

47.

Antman

Gibson

de Lemos

Giugliano

McCabe

Coussement

, Combination reperfusion therapy with abciximab and reduced dose reteplase: results from TIMI 14. Eur Heart J 2000; 21: 1944–53.

48.

Trial of abciximab with and without low-dose reteplase for acute myocardial infarction. The SPEED Investigators. Circulation 2000; 101: 2788–94.

49.

Giugliano

Roe

Staedische

. Restoration of epicardial and myocardial perfusion in acute ST-elevation myocardial infarction with combination eptifibatide and reduced-dose tenecteplase: dose-finding results from the INTEGRITI trial (abstract). Circulation 2001; 104 (suppl II): 538.

50.

Brener

Zeyer

Adgey

Vrobel

Ellis

Neuhaus

, Eptifibatide and low-dose tissue plasminogen activator in acute myocardial infarction: the integrilin and low-dose thrombosis in acute myocardial infarction (INTRO AMI) trial. J Am Coll Cardiol 2002; 39: 377–86.

51.

Reperfusion therapy for acute myocardial infarction with fibrinolytic therapy or combination reduced fibrinolytic therapy and platelet glycoprotein IIb/IIIa inhibition: the GUSTO V randomised trial. Lancet 2001; 357: 1905–14.

52.

Efficacy and safety of tenecteplase in combination with enoxaparin, abciximab, or unfractionated heparin: the ASSENT-3 randomised trial in acute myocardial infarction. ASSENT-3 investigators. Lancet 2001; 358: 605–13.

53.

Lincoff

Califf

van de Werf

Willerson

White

Armstrong

, Mortality at 1 year with combination platelet glycoprotein IIb/IIIa inhibition and reduced dose fibrinolytic therapy vs. conventional fibrinolytic therapy for acute myocardial infarction. JAMA 2002; 288: 2130–5.

54.

Antman

Louwerenburg

Baars

Wesdorp

Hamer

Bassand

, Enoxaparin as adjunctive antithrombin therapy for ST-elevation myocardial infarction: results of the ENTIRE-Thrombolysis in Myocardial Infarction (TIMI) 23 trial. Circulation 2002; 105: 1642–9.

55.

Lefkovits

Ivanhoe

Califf

Bergelson

Anderson

Stoner

, Effects of platelet glycoprotein IIb/IIIa receptor blockade by a chimeric monoclonal antibody (abciximab) on acute and six-month outcomes after percutaneous transluminal coronary angioplasty for acute myocardial infarction. Am J Cardiol 1996; 77: 1045–51.

56.

Azar

McKay

Thompson

Hirst

Mitchell

Fram

, Abciximab in primary coronary angioplasty for acute myocardial infarction improves short-and medium-term outcomes. J Am Coll Cardiol 1998; 32: 1996–2002.

57.

Neumann

Blasini

Schmitt

Alt

Dirschinger

Gawaz

, Effect of glycoprotein 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.

58.

Neumann

Kastrati

Schmitt

Blasini

Hadamitzky

Mehilli

, 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.

59.

Schomig

Kastrati

Dirschinger

Mehilli

Schricke

Pache

, Coronary stenting plus platelet glycoprotein IIb/IIIa blockade compared with tissue plasminogen activator in acute myocardial infarction. N Engl J Med 2000; 343: 385–91.

60.

Giri

Mitchel

Azar

Kiernan

Fram

McKay

, Results of primary percutaneous transluminal coronary angioplasty plus abciximab with or without stenting for acute myocardial infarction complicated by cardiogenic shock. Am J Cardiol 2002; 89: 126–31.

61.

Brener

Barr

Burchenal

Katz

George

Jones

, Randomized, placebo-controlled trial of platelet glycoprotein IIb/IIIa blockade with primary angioplasty for acute myocardial infarction. Circulation 1998; 98: 734–41.

62.

Montalescot

Barragan

Wittenberg

Ecollan

Elhadad

Villain

, Platelet glycoprotein IIb/IIIa inhibition with coronary stenting for acute myocardial infarction. N Engl J Med 2001; 344: 1895–903.

63.

Stone

Grines

Cox

Garcia

Tcheng

Griffin

, Comparison of angioplasty with stenting, with or without abciximab, in acute myocardial infarction. N Engl J Med 2002; 346: 957–66.

64.

van Hout

Bowman

Zelinger

Simoons

. Costs and effects in therapy for acute coronary syndromes: the case of abciximab in high-risk patients undergoing percutaneous transluminal coronary angioplasty in the EPIC study. Evaluation of 7E3 for the Prevention of Ischemic Complications. Am Heart J 1998; 135: S98–106.

65.

Comparative 30-day economic and clinical outcomes of platelet glycoprotein IIb/IIIa inhibitor use during elective percutaneous coronary intervention: Prairie ReoPro versus Integrilin Cost Evaluation (PRICE) Trial. PRICE Investigators. Am Heart J 2001; 141: 402–9.

66.

Zwart-van Rijkom

van Hout

. Cost-efficacy in interventional cardiology; results from the EPISTENT study. Evaluation of Platelet IIb/IIIa Inhibitor For Stenting Trial. Eur Heart J 2001; 22: 1476–84.

67.

Califf

. Evaluating the costs and effectiveness of cardiovascular therapies: who cares about economic analyses? Stat Med 2002; 21: 2889–97.

68.

Effects of clopidogrel in addition to aspirin in patients with acute coronary syndromes without ST-segment elevation. The CURE trial investigators. N Engl J Med 2001; 345: 494–502.

69.

Mehta

Yusuf

Peters

Bertrand

Lewis

Natarajan

, Effect of pretreatment with clopidogrel and aspirin followed by long-term therapy in patients undergoing percutaneous coronary intervention: the PCI-CURE study. Lancet 2001; 358: 527–33.

70.

Cohen

Demers

Gurfinkle

Turpie

Fromell

Goodman

, A comparison of low-molecular-weight heparins with unfractionated heparin for unstable coronary artery disease. N Engl J Med 1997; 337: 447–52.

71.

Cohen

Theroux

Weber

Laramee

Huynh

Borzak

, Combination therapy with tirofiban and enoxaparin in acute coronary syndromes. Int J Cardiol 1999; 71: 273–81.

72.

Cohen

Theroux

Frey

White

Borzak

Weber

, Antithrombotic Combination Using Tirofiban and Enoxaparin: the ACUTE II study (abstract). Circulation 2000; 102 (2 suppl): II-826.

73.

Ferguson

Antman

Bates

Cohen

Every

Harrington

, The use of enoxaparin and IIb/IIIa antagonists in acute coronary syndromes, including PCI: final results of the NICE 3 study (abstract). J Am Coll Cardiol 2001; 37: 365A.

74.

Young

Kereiakes

Grines

. Low-molecular-weight heparin therapy in percutaneous coronary intervention: the NICE 1 and NICE 4 trials. J Invas Cardiol 2000; 12 (E suppl): E14–8, E18-25.

75.

Kereiakes

Kleiman

Fry

Mwawasi

Lengerich

Maresh

, Dalteparin in combination with abciximab during percutaneous coronary intervention. Am Heart J 2001; 141: 348–52.

76.

Wallentin

. GUSTO-IV ACS (Global Utilisation of Streptokinase and t-PA for Occluded coronary arteries Trial IV in Acute Coronary Syndromes): substudy comparing outcomes for the combination of abciximab with standard unfractionated heparin or low molecular weight heparin. Presented at: 22nd Congress of the European Society of Cardiology, Amsterdam, August 28, 2000.

77.

Bhatt

Lincoff

. Combined use of eptifibatide and enoxaparin in patients undergoing percutaneous coronary intervention: the results of the CRUISE trial. Circulation 2001; 104: 384–5.

78.

Choussat

Montalescot

Collet

Gallois

Sotirov

Drobinski

, Low dose intravenous enoxaparin in elective percutaneous coronary intervention (abstract). Circulation 2001; 104 (2 suppl): II-706.

79.

Mukherjee

Mahaffey

Sparapani

Dyke

Roe

Moliterno

, The promise of combined LMW heparin and platelet glycoprotein IIb/IIIa inhibition: results from PARAGON B (abstract). Circulation 2000; 102 (2 suppl): II-591.

80.

Lincoff

Bittl

Harrington

Feit

Kleiman

Jackman

, Bivalirudin and provisional glycoprotein IIb/IIIa blockade compared with heparin and planned glycoprotein IIb/IIIa blockade during percutaneous coronary intervention: REPLACE-2 randomized trial. JAMA 2003; 289: 853–63.

81.

Smith

Dove

Jacobs

Kennedy

Kereiakes

Kern

, ACC/AHA guidelines for percutaneous coronary intervention. J Am Coll Cardiol 2001; 37: 1–66.