Skip to main content
SpringerLink
Log in

Unstable Angina Trials

PARAGON, PURSUIT, PRISM, PRISM-PLUS, and GUSTO-IV

  • Chapter
Platelet Glycoprotein IIb/IIIa Inhibitors in Cardiovascular Disease

Part of the book series: Contemporary Cardiology ((CONCARD))

  • 109 Accesses

Abstract

Unstable angina is part of the acute coronary syndrome (ACS) spectrum; it is related to non-Q-wave myocardial infarction and slightly more distantly related to Q-wave myocardial infarction. The diversity of conditions leading to unstable angina as well as the varying symptoms upon presentation have made the definition and classification of unstable angina difficult (1). The Global Unstable Angina Registry and Treatment Evaluation (GUARANTEE) study reported that one-third of hospitalized patients with cardiac chest pain had new or accelerated symptoms associated with exertion, whereas two-thirds had rest angina (2). This distinction is important, since patients with exertional angina may have a gradual worsening of an underlying atherosclerotic coronary arterial narrowing, as opposed to those with rest angina, who have an abrupt reduction in myocardial perfusion owing to a ruptured plaque (see Chapter 1). Angina at rest is often associated with electrocardiographic changes of ischemia and shares a similar underlying mechanism with threatened vessel closure following percutaneous coronary angioplasty, i.e., plaque disruption. Whether spontaneous or as a result of angioplasty, plaque rupture leads to exposure of the coronary arterial subendothelial components, platelet activation, and thrombus formation.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 249.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Fuster V, Chesebro JH. Mechanisms of unstable angina. N Engl J Med 1986;315:1023–1025.

    Article  PubMed  CAS  Google Scholar 

  2. Moliterno DJ, Aguirre FV, Cannon CP, et al., for the GUARANTEE Investigators. The Global Unstable Angina Registry and Treatment Evaluation. Circulation 1996;94:I.

    Google Scholar 

  3. Willerson JT, Golino P, Eidt J, Campbell WB, Buja LM. Specific platelet mediators and unstable coronary artery lesions: experimental evidence and potential clinical implications. Circulation 1989;80: 198–205.

    Article  PubMed  CAS  Google Scholar 

  4. Coller BS. The role of platelets in arterial thrombosis and the rationale for blockade of platelet GP IIb/ IIIa receptors as antithrombotic therapy. Eur Heart J 1995 ;16(Suppl L):11–15.

    Article  PubMed  CAS  Google Scholar 

  5. Théroux P, Ouimet H, McCans J, et al. Aspirin, heparin, or both to treat acute unstable angina. N Engl J Med 1988;319:1105–1111.

    Article  PubMed  Google Scholar 

  6. The RISC Group. Risk of myocardial infarction and death during treatment with low dose aspirin and intravenous heparin in men with unstable coronary artery disease. Lancet 1990;336:827–830.

    Article  Google Scholar 

  7. Wallentin LC, and the Research Group on Instability in Coronary Artery Disease in Southeast Sweden. Aspirin (75 mg/day) after an episode of unstable coronary artery disease: long-term effects on the risk for myocardial infarction, occurrence of severe angina and the need for revascularization. J Am Coll Cardiol 1991;18:1587–1593.

    Article  PubMed  CAS  Google Scholar 

  8. Cairns JA, Gent M, Singer J, et al. Aspirin, sulfinpyrazone, or both in unstable angina. N Engl J Med 1985; 313:1369–1375.

    Article  PubMed  CAS  Google Scholar 

  9. Lewis HDJ, Davis JW, Archibald DG, et al. Protective effects of aspirin against acute myocardial infarction and death in men with unstable angina. N Engl J Med 1983;309:396–403.

    Article  PubMed  Google Scholar 

  10. Antiplatelet Trialists’ Collaboration. 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. BMJ 1994;308:81–106.

    Article  Google Scholar 

  11. Antithrombotic Trialists’ Collaboration. Collaborative meta-analysis of randomised trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high risk patients. BMJ 2002;324: 71–86.

    Article  Google Scholar 

  12. Maffrand JP, Bernat A, Delebasse D, Defreyen G, Cazenave JP, Gordon JL. ADP plays a key role in thrombogenesis in rats. Thromb Haemost 1988;59:225–230.

    PubMed  CAS  Google Scholar 

  13. De Minno G, Cerbone AM, Mattioli PL, Turco S, Iovine C, Mancini M. Functionally thrombosthenic state in normal platelets following the administration of ticlopidine. J Clin Invest 1985;75:328–338.

    Article  PubMed  Google Scholar 

  14. Panak E, Maffrand JP, Picard-Fraire C, Vallee E, Blanchard J, Roncucci R. Ticlopidine: a promise for the prevention and treatment of thrombosis and its complications. Haemostasis 1983;13(Suppl 1):1–54.

    PubMed  Google Scholar 

  15. Balsano F, Rizzon P, Violi F, et al., and the Studio della Ticlopidina nell’ Angina Instabile Group. Antiplatelet treatment with ticlopidine in unstable angina. A controlled multicenter clinical trial. Circulation 1990;82:17–26.

    Article  PubMed  CAS  Google Scholar 

  16. CAPRIE Steering Commitee. A randomised, blinded, trial of clopidogrel versus aspirin in patients at risk of ischaemic events (CAPRIE). Lancet 1996;348:1329–1339.

    Article  Google Scholar 

  17. The Clopidogrel in Unstable Angina to Prevent Recurrent Events Trial Investigators. 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.

    Article  Google Scholar 

  18. The Platelet IIB/IIIA Antagonist for the Reduction of Acute Coronary Syndrome Events in a Global Organization Network (PARAGON)-B Investigators. Randomized, placebo-controlled trial of titrated intravenous lamifiban for acute coronary syndromes. Circulation 2002;105:316–321.

    Article  Google Scholar 

  19. The PARAGON Investigators. An international, randomized, controlled trial of lamifiban, a platelet glycoprotein IIB/IIIA inhibitor, heparin, or both in unstable angina. Circulation 1998;97:2386–2395.

    Article  Google Scholar 

  20. The 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; 338:1498–1505.

    Article  Google Scholar 

  21. The 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; 338:1488–1497.

    Article  Google Scholar 

  22. The PURSUIT Trial Investigators. Inhibition of platelet glycoprotein IIB/IIIA with eptifibatide in patients with acute coronary syndromes. N Engl J Med 1998;339:436–463.

    Article  Google Scholar 

  23. The 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;357:1915–1924.

    Article  Google Scholar 

  24. The 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;330:956–961.

    Article  Google Scholar 

  25. 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.

    Article  Google Scholar 

  26. Lincoff AM, Califf RM, Anderson KM, et al. Evidence for prevention of death and myocardial infarction with platelet membrane glycoprotein IIB/IIIA receptor blockade by abciximab (c7E3 Fab) among patients with unstable angina undergoing percutaneous coronary revascularization. J Am Coll Cardiol 1997;30:149–156.

    Article  PubMed  CAS  Google Scholar 

  27. Topol EJ, Ferguson JJ, Weisman HF, et al., on behalf of the EPIC Investigators. Long term protection from myocardial ischemic events in a randomized trial of brief integrin β3 blockade wwith percutaneous intervention. JAMA 1997;278:479–484.

    Article  PubMed  CAS  Google Scholar 

  28. The EPISTENT Investigators. Randomised placebo-controlled and balloon-angioplasty-controlled trial to assess safety of coronary stenting with use of platelet glycoprotein-IIIB/IIIA blockade. The EPISTENT Investigators. Evaluation of platelet IIB/IIIA inhibitor for stenting. Lancet 1998;352:87–92.

    Article  Google Scholar 

  29. The CAPTURE Investigators. Randomised placebo-controlled trial of abciximab before and during coronary interventions in refractory unstable angina: the CAPTURE study. Lancet 1997;349:1429–1435.

    Article  Google Scholar 

  30. Topol EJ, Moliterno DJ, Herrmann HC, et al. Comparison of two platelet glycoprotein IIb/Illa inhibitors, tirofiban and abciximab, for the prevention of ischemic events with percutaneous coronary revascularization. N Engl J Med 2001;344:1888–1894.

    Article  PubMed  CAS  Google Scholar 

  31. Stone G, Moliterno D, Bertrand M, et al. Impact of clinical syndrome acuity on the differential response to 2 glycoprotein IIB/IIIA Inhibitors in patients undergoing coronary stenting. The TARGET Trial. Circulation 2002;105:2347–2354.

    Article  PubMed  CAS  Google Scholar 

  32. Théroux P, Kouz S, Roy L, et al., on behalf of the Investigators. Platelet membrane receptor glycoprotein IIB/IIIA antagonism in unstable angina. The Candian Lamifiban Study. Circulation 1996;94:899–905.

    Article  PubMed  Google Scholar 

  33. Topol EJ, Califf RM, Van de Werf F, et al. Perspectives on large-scale cardiovascular clinical trials for the new millennium. Circulation 1997;95:1072–1082.

    Article  PubMed  CAS  Google Scholar 

  34. Steiner B, Hofer U, Wittke B, et al. Plasma concentrations of lamifiban and glycoprotein IIb-IlIa receptor occupancy best predict clinical outcome in patients with unstable angina: results from PARAGON A. Eur Heart J 1998;19(abstract):598.

    Google Scholar 

  35. 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;139:563–566.

    Article  PubMed  CAS  Google Scholar 

  36. Théroux P, Kouz S, Roy L., et al. Platelet membrane receptor glycoprotein IIB/IIIA antagonism in unstable angina. The Canadian Lamifiban Study. Circulation 1996;94:899–905.

    Article  PubMed  Google Scholar 

  37. Schulman SP, Goldschmidt-Clermont PJ, Topol EJ, et al. Effects of Integrelin, a platelet glycoprotein IIIa receptor antagonist, in unstable angina: a randomized multicenter trial. Circulation 1996;94:2083–2089.

    Article  PubMed  CAS  Google Scholar 

  38. Phillips DR, Teng W, Arfsten A, et al. Effect of Ca2+ on GP IIb-IIIa binding and inhibition of platelet aggregation by reductions in the concentration of ionized calcium in plasma anticoagulated with citrate. Circulation 1997;96:1488–1494.

    Article  PubMed  CAS  Google Scholar 

  39. Moliterno DJ, Topol EJ. Meta-analysis of platelet GP IIB/IIIA antagonist randomized clinical trials: consistent, durable, salutary effects. Circulation 1997;96:I-475.

    Google Scholar 

  40. Topol EJ. Toward a new frontier in myocardial reperfusion therapy: emerging platelet preeminence. Circulation 1997;97:211–218.

    Article  Google Scholar 

  41. Kong DF, Califf RM, Miller DP, et al. Clinical outcomes of therapeutic agents that block the platelet glycoprotein inhibitor integrin in ischemic heart disease. Circulation 1998;98:2829–2935.

    Article  PubMed  CAS  Google Scholar 

  42. Boersma E, Harrington R, Moliterno D, 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.

    Article  PubMed  CAS  Google Scholar 

  43. Roffi M, Chew D, 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.

    Article  PubMed  CAS  Google Scholar 

  44. Newby L, Ohman E, Christenson R, et al., for the PARAGON-B Investigators. 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.

    Article  PubMed  CAS  Google Scholar 

  45. 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; 354:1757–1762.

    Article  PubMed  CAS  Google Scholar 

  46. 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;103:201–206.

    Article  PubMed  CAS  Google Scholar 

  47. 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 (alphaIIbbeta3) inhibitors. Blood 1998;92: 3240–3249.

    PubMed  CAS  Google Scholar 

  48. Steinhubl 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;100:1977–1982.

    Article  PubMed  CAS  Google Scholar 

  49. Chew DP, Moliterno DJ. A critical appraisal of platelet glycoprotein IIB/IIIA inhibition. J Am Coll Cardiol 2000;36:2028–2035.

    Article  PubMed  CAS  Google Scholar 

  50. Oler A, Whooley MA, Oler J, Grady D. Adding heparin to aspirin reduces the incidence of myocardial infarction and deat in patients with unstable angina: a meta-analysis. JAMA 1996;2276:811–815.

    Google Scholar 

  51. Braunwald E, Antman E, Beasley J, 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.

    Article  PubMed  Google Scholar 

Download references

Authors
  1. David J. Moliterno MD
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Department of Cardiovascular Medicine, The Cleveland Clinic Foundation, Cleveland, OH, USA

    A. Michael Lincoff MD

Rights and permissions

Reprints and permissions

Copyright information

© 2003 Springer Science+Business Media New York

About this chapter

Cite this chapter

Moliterno, D.J. (2003). Unstable Angina Trials. In: Lincoff, A.M. (eds) Platelet Glycoprotein IIb/IIIa Inhibitors in Cardiovascular Disease. Contemporary Cardiology. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-59259-376-7_10

Download citation

  • DOI: https://doi.org/10.1007/978-1-59259-376-7_10

  • Publisher Name: Humana Press, Totowa, NJ

  • Print ISBN: 978-1-61737-408-1

  • Online ISBN: 978-1-59259-376-7

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation