Skip to main content
SpringerLink
Log in

Implications of the GUSTO Trial for Thrombolytic Therapy

  • Leading Article
  • Published:
Drugs Aims and scope Submit manuscript

Summary

This article discusses the impact of previous clinical observations on the development of the GUSTO-I protocol, particularly the absence of a survival benefit of alteplase (rt-PA) over streptokinase in the GISSI-2/International Study Group and ISIS-3 trials in spite of a higher efficacy for clot lysis. The demonstrated superiority of front-loaded alteplase in this large trial is translated into useful guidelines for the practising clinician. Risk-benefit analysis indicates that, in general, this thrombolytic regimen is most indicated in patients presenting with large amounts of jeopardised ischaemic myocardium in the absence of a particularly increased risk of haemorrhagic stroke. Finally, the impact of this study for future development in the field of acute coronary syndromes is evaluated, more specifically for the design of new trials with new fibrinolytic and antithrombotic agents. These include mutants of alteplase, staphylokinase, direct antithrombins and inhibitors of the glycoprotein IIb/IIIa platelet receptor.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. International Study Group. In-hospital mortality and clinical course of 20 981 patients with suspected acute myocardial infarction randomised between alteplase and streptokinase with or without heparin. Lancet 1990 Jul 14; 336: 71–5

    Article  Google Scholar 

  2. Gruppo Italiano per lo Studio della Sopravvivenza nell’Infarto Miocardico. GISSI-2: a factorial randomised trial of alteplase versus streptokinase and heparin versus no heparin among 12 490 patients with acute myocardial infarction. Lancet 1990; 336: 65–71

    Google Scholar 

  3. ISIS-3 (Third International Study of Infarct Survival) Collaborative Group. ISIS-3: a randomised comparison of streptokinase vs tissue plasminogen activator vs anistreplase and of aspirin plus heparin vs aspirin alone among 41 299 cases of suspected acute myocardial infarction. Lancet 1993; 339: 753–70

    Google Scholar 

  4. Hsia J, Hamilton WP, Kleiman N, et al. A comparison between heparin and low-dose aspirin as adjunctive therapy with tissue plasminogen activator for acute myocardial infarction. N Engl J Med 1990; 323: 1433–7

    Article  PubMed  CAS  Google Scholar 

  5. Bleich SD, Nichols TC, Schumacher RR, et al. Effect of heparin on coronary arterial patency after thrombolysis with tissue plasminogen activator in acute myocardial infarction. Am J Cardiol 1990; 66: 1412–7

    Article  PubMed  CAS  Google Scholar 

  6. de Bono DP, Simoons ML, Tijssen J, et al. Effect of early intravenous heparin on coronary patency, infarct size and bleeding complications after alteplase thrombolysis: results of a randomised double blind European Cooperative Study Group trial. Br Heart J 1992; 67: 122–8

    Article  PubMed  Google Scholar 

  7. Neuhaus KL, Feuerer W, Jeep-Tebbe S, et al. Improved thrombolysis with a modified dose regimen of recombinant tissue-type plasminogen activator. J Am Coll Cardiol 1989; 14: 1566–9

    Article  PubMed  CAS  Google Scholar 

  8. Neuhaus KL, Von Essen R, Tebbe U, et al. Improved thrombolysis in acute myocardial infarction with front-loaded administration of alteplase: results of the rt-PA-APSAC patency study (TAPS). J Am Coll Cardiol 1992; 19: 885–91

    Article  PubMed  CAS  Google Scholar 

  9. Topol EJ, Califf RM, George BS, et al. Coronary arterial thrombolysis with combined infusion of recombinant tissue-type plasminogen activator and urokinase in patients with acute myocardial infarction. Circulation 1988; 77: 1100–7

    Article  PubMed  CAS  Google Scholar 

  10. Califf RM, Topol EJ, Stack RS, et al. Evaluation of combination of thrombolytic therapy and timing of cardiac catheterization in acute myocardial infarction: results of thrombolysis and angioplasty in myocardial infarction — phase 5 randomized trial. Circulation 1991; 83: 1543–56

    Article  PubMed  CAS  Google Scholar 

  11. Grines CL, Nissen SE, Booth DC, et al. Aprospective, randomized trial comparing combination half-dose tissue-type plasminogen activator and streptokinase with full-dose tissue-type plasminogen activator. Circulation 1991; 84: 540–9

    Article  PubMed  CAS  Google Scholar 

  12. GUSTO Investigators. An international randomized trial comparing four thrombolytic strategies for acute myocardial infarction. N Engl J Med 1993; 329: 673–82

    Article  Google Scholar 

  13. GUSTO Angiographic Investigators. The effects of tissue plasminogen activator, streptokinase, or both on coronary-artery patency, ventricular function, and survival after acute myocardial infarction. N Engl J Med 1993; 329: 1615–22

    Article  Google Scholar 

  14. Califf RM, Topol EJ, Van de Werf F, et al. One year follow-up from the GUSTO-I trial. Circulation 1994; 90: 1–325

    Article  Google Scholar 

  15. Simes J, Holmes DR, Ross A, et al. The link between the angiographic substudy and mortality outcomes in a large randomized trial of myocardial infarction: the importance of early and complete infarct-artery reperfusion. Circulation 1995; 91: 1923–8

    Article  PubMed  CAS  Google Scholar 

  16. Kleiman NS, White HD, Ohman EM, et al. Mortality within 24 hours of thrombolysis for myocardial infarction: the importance of early reperfusion. Circulation 1994; 90: 2658–65

    Article  PubMed  CAS  Google Scholar 

  17. Lee KL, Woodlief LH, Topol EJ, et al. Predictors of 30-day mortality in the era of reperfusion for acute myocardial infarction: results from an international trial of 41 021 patients. Circulation 1995; 91: 1659–68

    Article  PubMed  CAS  Google Scholar 

  18. Gore JM, Granger CB, Simoons ML, et al. Stroke after thrombolysis: mortality and functional outcomes in the GUSTO-I trial. Circulation 1995; 92: 2811–8

    Article  PubMed  CAS  Google Scholar 

  19. Van de Werf F, Topol EJ, Lee KL, et al. Variations in patient management and outcomes for acute myocardial infarction in the United States and other countries: results from the GUSTO trial. JAMA 1995; 273: 1586–91

    Article  PubMed  Google Scholar 

  20. Pilote L, Califf RM, Sapp S, et al. Regional variation across the united states in the management of acute myocardial infarction. N Engl J Med 1995; 333: 565–72

    Article  PubMed  CAS  Google Scholar 

  21. Mark DB, Hlatky MA, Califf RM, et al. Cost effectiveness of thrombolytic therapy with tissue plasminogen activator as compared with streptokinase for acute myocardial infarction. N Engl J Med 1995; 332: 1418–24

    Article  PubMed  CAS  Google Scholar 

  22. Holmes DR, Bates ER, Kleiman NS, et al. Contemporary reperfusion therapy for cardiogenic shock: the GUSTO-I trial experience. J Am Coll Cardiol 1995; 26: 668–74

    Article  PubMed  Google Scholar 

  23. Barbash GI, Reiner J, White HD, et al. Evaluation of paradoxic beneficial effects of smoking in patients receiving thrombolytic therapy for acute myocardial infarction: mechanism of the ‘smoker’s paradox’ from the GUSTO-I trial, with an-giographic insights. J Am Coll Cardiol 1995; 26: 1222–8

    Article  PubMed  CAS  Google Scholar 

  24. Langer A, Krucoff MW, Klootwijk P, et al. Noninvasive assessment of speed and stability of infarct-related artery reperfusion: results of the GUSTO ST segment monitoring study. J Am Coll Cardiol 1995; 25: 1552–7

    Article  PubMed  CAS  Google Scholar 

  25. Reiner JS, Lundergan CF, van den Brand M, et al. Early angiography cannot predict postthrombolytic coronary reocclusion: observations from the GUSTO angiographic study. J Am Coll Cardiol 1994; 24: 1439–44

    Article  PubMed  CAS  Google Scholar 

  26. Mark DB, Naylor CD, Hlatky MA, et al. Use of medical resources and quality of life after acute myocardial infarction in Canada and the United States. N Engl J Med 1994; 331: 1130–5

    Article  PubMed  CAS  Google Scholar 

  27. Topol EJ, Armstrong P, Van de Werf F, et al. Confronting the issues of patient safety and investigator conflict of interest in an international clinical trial of myocardial reperfusion. J Am Coll Cardiol 1992; 19: 1123–8

    Article  PubMed  CAS  Google Scholar 

  28. Ridker PM, Marder VJ, Hennekens CH. Large scale trials of thrombolytic therapy for acute myocardial infarction GISSI-2, ISIS-3, and GUSTO-1. Ann Intern Med 1993; 119: 530–2

    PubMed  CAS  Google Scholar 

  29. Sleight P. Thrombolysis after GUSTO: a European perspective. J Myo Isch 1993; 8: 25–30

    Google Scholar 

  30. Topol E. Textbook of interventional cardiology. Philadelphia (PA): W.B. Saunders, 1994: 103

    Google Scholar 

  31. Boersma H, vander Vlugt MJ, Arnold AER, et al. Estimated gain in life expectancy: a simple tool to select optimal reperfusion treatment in individual patients with evolving myocardial infarction. Eur Heart J 1996; 17: 64–75

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Cardiology, University Hospital Gasthuisberg, Herestraat 49, B-3000, Leuven, Belgium

    Frans Van de Werf

Authors
  1. Frans Van de Werf
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Van de Werf, F. Implications of the GUSTO Trial for Thrombolytic Therapy. Drugs 52, 307–312 (1996). https://doi.org/10.2165/00003495-199652030-00001

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/00003495-199652030-00001

Keywords

Search

Navigation