American Heart Journal
Volume 146, Issue 5 , Pages 764-774 , November 2003

Optimizing glycoprotein IIb/IIIa receptor antagonist use for the non-ST–segment elevation acute coronary syndromes: risk stratification and therapeutic intervention

  • James L Januzzi, MD

      Affiliations

    • Cardiology Divisions, Massachusetts General Hospital, Boston, Mass, USA
    • Corresponding Author InformationReprint requests: William E. Boden, MD, Director, Cardiology Division, Hartford Hospital, 80 Seymour Street, Box 5037, Hartford, CT, 06102-5037, USA.
  • ,
  • Christopher P Cannon, MD

      Affiliations

    • Brigham and Women's Hospital, Boston, Mass, USA
  • ,
  • Pierre Theroux, MD

      Affiliations

    • Montreal Heart Institute, Montreal, Quebec, Canada
  • ,
  • William E Boden, MD

      Affiliations

    • Hartford Hospital, Hartford, Conn, USA

Received 30 September 2002 ,Accepted 13 May 2003.

References 

  1. Braunwald E, Antman EM, Beasley JW, et al.  ACC/AHA guideline update for the management of patients with unstable angina and non-ST-segment elevation myocardial infarction—2002 (summary article: 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)). Circulation. 2002;106:1893–1900
  2. Boersma E, Harrington RA, Moliterno DJ, et al.  Platelet glycoprotein IIb/IIIa inhibitors in acute coronary syndromes (a meta-analysis of all major randomised clinical trials). Lancet. 2002;359:189–198
  3. Peterson E, Canto J, Pollack C, et al. Early use of glycoprotein 2b3a inhibitors and outcomes in non-ST elevation MI: observations from the NRMI-4. J Am Coll Cardiol 2002;39(Suppl A):
  4. 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
  5. The EPILOG Investigators . Platelet glycoprotein IIb/IIIa receptor blockade and low-dose heparin during percutaneous coronary revascularization. N Engl J Med. 1997;336:1689–1696
  6. 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;349:1422–8
  7. 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
  8. 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
  9. 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;285:2468–2473
  10. Tcheng JE. Glycoprotein IIb/IIIa receptor inhibitors (putting the EPIC, IMPACT II, RESTORE, and EPILOG trials into perspective). Am J Cardiol. 1996;78:35–40
  11. Bhatt DL, Topol EJ. Current role of platelet glycoprotein IIb/IIIa inhibitors in acute coronary syndromes. JAMA. 2000;284:1549–1558
  12. Coller BS. Platelet GPIIb/IIIa antagonists (the first anti-integrin receptor therapeutics). J Clin Invest. 1997;100(11 Suppl):S57–60
  13. Randomised placebo-controlled trial of abciximab before and during coronary intervention in refractory unstable angina: the CAPTURE Study. Lancet 1997;349:1429–35
  14. Boersma E, Akkerhuis KM, Theroux P, et al.  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;100:2045–2048
  15. Simoons ML. 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;357:1915–1924
  16. 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;106:1470–1476
  17. Scarborough RM. Development of eptifibatide. Am Heart J. 1999;138:1093–1104
  18. 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
  19. Roffi M, Chew D, Mukherjee D, et al.  Platelet glycoprotein IIb/IIIa inhibition in acute coronary syndromes (gradient of benefit related to the revascularization strategy). Eur Heart J. 2002;23:1441
  20. Lincoff AM, Harrington RA, Califf RM, et al.  A comparison of aspirin plus tirofiban with aspirin plus heparin for unstable angina. Platelet Receptor Inhibition in Ischemic Syndrome Management (PRISM) Study Investigators. Circulation. 2000;102:1093–1100
  21. Labinaz M, Kilaru R, Pieper K, et al.  Outcomes of patients with acute coronary syndromes and prior coronary artery bypass grafting (results from the platelet glycoprotein IIb/IIIa in unstable angina: receptor suppression using integrilin therapy (PURSUIT) trial). Circulation. 2002;105:322–327
  22. Hasdai D, Holmes DR, Criger DA, et al.  Age and outcome after acute coronary syndromes without persistent ST-segment elevation. Am Heart J. 2000;139:858–866
  23. Hasdai D, Harrington RA, Hochman JS, 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;36:685–692
  24. Greenbaum AB, Harrington RA, Hudson MP, et al.  Therapeutic value of eptifibatide at community hospitals transferring patients to tertiary referral centers early after admission for acute coronary syndromes. PURSUIT Investigators. J Am Coll Cardiol. 2001;37:492–498
  25. 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
  26. Inhibition of the 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
  27. Theroux P, Alexander J, Pharand C, et al.  Glycoprotein IIb/IIIa receptor blockade improves outcomes in diabetic patients presenting with unstable angina/non-ST-elevation myocardial infarction (results from the Platelet Receptor Inhibition in Ischemic Syndrome Management in Patients Limited by Unstable Signs and Symptoms (PRISM-PLUS) study). Circulation. 2000;102:2466–2472
  28. Januzzi JL, Snapinn SM, DiBattiste PM, et al.  Benefits and safety of tirofiban among acute coronary syndrome patients with mild to moderate renal insufficiency. Circulation. 2002;105:2359–2364
  29. Januzzi JL, Sabatine MS, Wan Y, et al.  Interactions between age, outcome of acute coronary syndromes, and tirofiban therapy. Am J Cardiol. 2003;91:457–461
  30. Januzzi JL, Hahn SS, Chae CU, et al.  Effects of tirofiban plus heparin versus heparin alone on troponin I levels in patients with acute coronary syndromes. Am J Cardiol. 2000;86:713–717
  31. Theroux P, Alexander J, Dupuis J, et al.  Upstream use of tirofiban in patients admitted for an acute coronary syndrome in hospitals with or without facilities for invasive management. PRISM-PLUS Investigators. Am J Cardiol. 2001;87:375–380
  32. Effects of tissue plasminogen activator and a comparison of early invasive and conservative strategies in unstable angina and non-Q-wave myocardial infarction. Results of the TIMI IIIB Trial. Thrombolysis in Myocardial Ischemia. Circulation 1994;89:1545–56
  33. Boden WE, O'Rourke RA, Crawford MH, et al.  Outcomes in patients with acute non-Q-wave myocardial infarction randomly assigned to an invasive as compared with a conservative management strategy. Veterans Affairs Non-Q-Wave Infarction Strategies in Hospital (VANQWISH) Trial Investigators. N Engl J Med. 1998;338:1785–1792
  34. McCullough PA, O'Neill WW, Graham M, et al.  A prospective randomized trial of triage angiography in acute coronary syndromes ineligible for thrombolytic therapy (results of the medicine versus angiography in thrombolytic exclusion (MATE) trial). J Am Coll Cardiol. 1998;32:596–605
  35. 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
  36. Cannon CP, Weintraub WS, Demopoulos LA, et al.  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;344:1879–1887
  37. Fox KA, Poole-Wilson PA, Henderson RA, et al.  Interventional versus conservative treatment for patients with unstable angina or non-ST-elevation myocardial infarction (the British Heart Foundation RITA 3 randomised trial. Randomized Intervention Trial of unstable Angina). Lancet. 2002;360:743–751
  38. Alpert JS, Thygesen K, Antman E, et al.  Myocardial infarction redefined—a consensus document of The Joint European Society of Cardiology/American College of Cardiology Committee for the redefinition of myocardial infarction. J Am Coll Cardiol. 2000;36:959–969
  39. Neumann F, Kastrati A, Pogatsa-Murray G, et al. Assessment of the value of cooling-off strategy (extended antithrombotic pretreatment) in patients with unstable coronary syndromes treated invasively: the Intracoronary Stenting with Antithrombotic Regimen Cooling-off (ISAR-COOL) Trial. Presented at: Late Breaking Clinical Trials, American Heart Association, November 17–20, 2002; Chicago, Ill
  40. Antman EM, Cohen M, Bernink PJ, et al.  The TIMI risk score for unstable angina/non-ST elevation MI (a method for prognostication and therapeutic decision making). JAMA. 2000;284:835–842
  41. Scirica BM, Cannon CP, Antman EM, et al.  Validation of the thrombolysis in myocardial infarction (TIMI) risk score for unstable angina pectoris and non-ST-elevation myocardial infarction in the TIMI III registry. Am J Cardiol. 2002;90:303–305
  42. Boersma E, Pieper KS, Steyerberg EW, et al.  Predictors of outcome in patients with acute coronary syndromes without persistent ST-segment elevation (results from an international trial of 9461 patients. The PURSUIT Investigators). Circulation. 2000;101:2557–2567
  43. Sabatine MS, Januzzi JL, Snapinn S, et al.  A risk score system for predicting adverse outcomes and magnitude of benefit with glycoprotein IIb/IIIa inhibitor therapy in patients with unstable angina pectoris. Am J Cardiol. 2001;88:488–492
  44. Solomon DH, Stone PH, Glynn RJ, et al.  Use of risk stratification to identify patients with unstable angina likeliest to benefit from an invasive versus conservative management strategy. J Am Coll Cardiol. 2001;38:969–976
  45. Samaha FF, Kimmel SE, Kizer JR, et al.  Usefulness of the TIMI risk score in predicting both short- and long- term outcomes in the Veterans Affairs Non-Q-Wave Myocardial Infarction Strategies In-Hospital (VANQWISH) Trial. Am J Cardiol. 2002;90:922–926
  46. Morrow DA, Antman EM, Snapinn SM, et al.  An integrated clinical approach to predicting the benefit of tirofiban in non-ST elevation acute coronary syndromes (application of the TIMI risk score for UA/NSTEMI in PRISM-PLUS). Eur Heart J. 2002;23:223–229
  47. Morrow D, Sabatine M, Cannon C, et al.  Benefit of tirofiban among patients treated without coronary intervention (application of the TIMI risk score for unstable angina and non-ST elevation MI in PRISM-PLUS). Circulation. 2002;104(Suppl II):782; (a)
  48. Malmberg K, Yusuf S, Gerstein HC, et al.  Impact of diabetes on long-term prognosis in patients with unstable angina and non-Q-wave myocardial infarction (results of the OASIS (Organization to Assess Strategies for Ischemic Syndromes) Registry). Circulation. 2000;102:1014–1019
  49. Kleiman NS, Lincoff AM, Kereiakes DJ, et al.  Diabetes mellitus, glycoprotein IIb/IIIa blockade, and heparin (evidence for a complex interaction in a multicenter trial). Circulation. 1998;97:1912–1920
  50. Marso SP, Lincoff AM, Ellis SG, 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;100:2477–2484
  51. Roffi M, Chew DP, Mukherjee D, et al.  Platelet glycoprotein IIb/IIIa inhibitors reduce mortality in diabetic patients with non-ST-segment-elevation acute coronary syndromes. Circulation. 2001;104:2767–2771
  52. Sabatine MS, Braunwald E. Will diabetes save the platelet blockers?. Circulation. 2001;104:2759–2761
  53. 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;340:1623–1629
  54. 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;354:1757–1762
  55. Newby LK, Ohman EM, Christenson RH, et al.  Benefit of glycoprotein IIb/IIIa inhibition in patients with acute coronary syndromes and troponin t-positive status (the paragon-B troponin T substudy). Circulation. 2001;103:2891–2896
  56. Januzzi JL, Chae CU, Sabatine MS, et al.  Elevation in serum troponin i predicts the benefit of tirofiban. J Thromb Thrombolysis. 2001;11:211–215
  57. Lindahl B, Diderholm E, Lagerqvist B, et al.  Mechanisms behind the prognostic value of troponin T in unstable coronary artery disease (a FRISC II substudy). J Am Coll Cardiol. 2001;38:979–986
  58. Morrow DA, Cannon CP, Rifai N, et al.  Ability of minor elevations of troponins I and T to predict benefit from an early invasive strategy in patients with unstable angina and non-ST elevation myocardial infarction (results from a randomized trial). JAMA. 2001;286:2405–2412
  59. Heeschen C, van Den Brand MJ, Hamm CW, et al.  Angiographic findings in patients with refractory unstable angina according to troponin T status. Circulation. 1999;100:1509–1514
  60. Zhao XQ, Theroux P, Snapinn SM, et al.  Intracoronary thrombus and platelet glycoprotein IIb/IIIa receptor blockade with tirofiban in unstable angina or non-Q-wave myocardial infarction (angiographic results from the PRISM-PLUS trial (Platelet receptor inhibition for ischemic syndrome management in patients limited by unstable signs and symptoms)). Circulation. 1999;100:1609–1615
  61. Antman EM, Cohen M, Radley D, et al.  Assessment of the treatment effect of enoxaparin for unstable angina/non-Q-wave myocardial infarction (TIMI 11B-ESSENCE meta-analysis). Circulation. 1999;100:1602–1608
  62. Long-term low-molecular-mass heparin in unstable coronary-artery disease: FRISC II prospective randomised multicentre study. FRagmin and Fast Revascularisation during InStability in Coronary artery disease Investigators. Lancet 1999;354:701–7
  63. Cohen M, Theroux P, Borzak S, et al.  Randomized double-blind safety study of enoxaparin versus unfractionated heparin in patients with non-ST-segment elevation acute coronary syndromes treated with tirofiban and aspirin (the ACUTE II study. The Antithrombotic Combination Using Tirofiban and Enoxaparin). Am Heart J. 2002;144:470–477
  64. Goodman S, Fitchett D, Armstrong P, et al. The INTegrilin and Enoxaparin Randomized Assessment of Acute Coronary Syndrome Treatment (INTERACT) trial. Presented at: Late Breaking Clinical Trials, American College of Cardiology, March 17–20, 2002; Atlanta, Ga
  65. Young JJ, Kereiakes DJ, Grines CL. Low-molecular-weight heparin therapy in percutaneous coronary intervention (the NICE 1 and NICE 4 trials. National Investigators Collaborating on Enoxaparin Investigators). J Invasive Cardiol. 2000;12(Suppl E):E14–18 discussion E25–8
  66. Fox KA, Antman EM, Cohen M, et al.  Comparison of enoxaparin versus unfractionated heparin in patients with unstable angina pectoris/non-ST-segment elevation acute myocardial infarction having subsequent percutaneous coronary intervention. Am J Cardiol. 2002;90:477–482
  67. Yusuf S, Zhao F, Mehta SR, et al.  Effects of clopidogrel in addition to aspirin in patients with acute coronary syndromes without ST-segment elevation. N Engl J Med. 2001;345:494–502
  68. Assali AR, Salloum J, Sdringola S, et al.  Effects of clopidogrel pretreatment before percutaneous coronary intervention in patients treated with glycoprotein IIb/IIIa inhibitors (abciximab or tirofiban). Am J Cardiol. 2001;88:884–886 A6
  69. 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;344:1888–1894
  70. Bonz AW, Lengenfelder B, Strotmann J, et al.  Effect of additional temporary glycoprotein IIb/IIIa receptor inhibition on troponin release in elective percutaneous coronary interventions after pretreatment with aspirin and clopidogrel (TOPSTAR trial). J Am Coll Cardiol. 2002;40:662–668
  71. Steinhubl SR, Berger PB, Mann JT, et al.  Early and sustained dual oral antiplatelet therapy following percutaneous coronary intervention (a randomized controlled trial). JAMA. 2002;288:2411–2420
  72. Kereiakes DJ, Montalescot G, Antman EM, et al.  Low-molecular-weight heparin therapy for non-ST-elevation acute coronary syndromes and during percutaneous coronary intervention (an expert consensus). Am Heart J. 2002;144:615–624
  73. Mehta SR, Yusuf S, Peters RJ, et al.  Effects of pretreatment with clopidogrel and aspirin followed by long- term therapy in patients undergoing percutaneous coronary intervention (the PCI-CURE study). Lancet. 2001;358:527–533

PII: S0002-8703(03)00437-X

doi: 10.1016/S0002-8703(03)00437-X

American Heart Journal
Volume 146, Issue 5 , Pages 764-774 , November 2003