Rational Pharmacotherapy in Cardiology

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It is reported that the implementation in clinical practice thrombolytic (fibrinolytic) therapy resulted inmortality reduction during firstmonth after myocardial infarction from 17-18% to 5-8%. Different details of this therapy are considered: terms of thrombolysis since the beginning of myocardial infarction, alternative methods of coronary blood flow recovery , indications and contraindications, complications and side effects, estimation of thrombolysis efficacy. Fibrin-selective and fibrin-non-selective drugs are presented. Different fibrinolytics are described: streptokinase, anistreplase, alteplase, reteplase, tenekteplase. The results of large randomized clinical trials devoted to fibrinolytic therapy of myocardial infarction are analyzed: GISSI, ISSIS, TIMI, GUSTO, INJECT, ASSENT. The possibility to increase in efficacy and safety of fibrinolytics by their combination with acetylsalicylic acid, IIb/IIIa receptor inhibitors and heparins are discussed.

About the Authors

E. V. Konstantinova
Russian state medical University of Roszdrav
Russian Federation
Department of faculty therapy named after A. I. Nesterov

A. V. Magnitskyi
Russian state medical University of Roszdrav
Russian Federation
Department of faculty therapy named after A. I. Nesterov

N. A. Schostak
Russian state medical University of Roszdrav
Russian Federation
Department of faculty therapy named after A. I. Nesterov


1. Davies M.J. The pathophysiology of acute coronary syndromes. Heart, 2000; 83: 361-6.

2. Чазов Е.И., Андреенко Г .В. Экспериментальное обоснование терапии лизирующими препаратами. В кн.: Совещание по применению антикоагулянтов. Л.; 1961.

3. Fletcher A.P ., Alkjaersing N., Smyrniotis F .E. et al. The treatment of patients suffering from early MI with massive and prolonged SK therapy. Trans. Assoc. Am. Phys. 1958; 71: 287.

4. Gruppo Italiano per lo Studio della Streptochinasi nell' Infarcto Miocardico (GISSI). Effectiveness of intravenous thrombolytic treatment in acutemyocardial infarction. Lancet 1986; 1: 397-402.

5. ISIS-2 (Second International Study of Infarct Survival) Collaborative Group. Randomized trial of intravenous streptokinase, oral aspirin, both, or neither among 17,187 cases of suspected acute myocardial infarction: ISIS-2. Ibid. 1988; 2: 349-360.

6. The GUSTO Investigators. An international randomized trial comparing four thrombolytic strategies for acute myocardial infarction. N. Engl. J. Med 1993; 329: 673-682.

7. Hasai B., Begar S.,Wallentin L. et al. A prospective survey of the characteristics, treatment and outcomes of patients with acute coronary syndromes in Europe and the Mediterranean basin. The Euro Heart Survey of Acute Coronary Syndromes (Euro Heart Survey ACS). Eur . Heart J. 2002; 15 (1): 1190-2001.

8. De Vreede J.J., Gorgels A.P ., Verstraaten G.M. et al. Did prognosis after acute myocardial infarction change during the past 30 years? A meta-analysis. J. Am. Coll. Cardiol., 1991; 18: 698-706.

9. Tunstall-Pedoe H., et al.Myocardial infarction and coronary deaths in theWorld Health OrganizationMONICA Project. Registration procedures, event rates, and case-fatality rates in 38 populations from 21 countries in four continents. Circulation. 1994; 90:583-612.

10. The Task Force on the Management of Acute Myocardial Infarction of the European Society of Cardiology. Acute myocardial infarction: pre-hospital and in-hospital management. Eur Heart J 1996; 17:43-63.

11. Lowel H., Lewis M., Hormann A.. Prognostic significance of the prehospital phase in acute myocardial infarction. Results of the Augsburg Infarct Registry 1985-1988 (German). Dtsch Med Wochenschr 1991; 116: 729-733.

12. Boersma E., Maas A.C., Deckers J.W., Simoons M.L. Early thrombolytic treatment in acute myocardial infarction: reappraiisal of the golden hour . Lancet 1996; 348: 771-775.

13. Stern R, Arntz H.R. Prehospital thrombolysis in acutemyocardial infarction. Eur J Emerg Med. 1998; 5:471-479.

14. Late assessment of thrombolytic efficacy (LATE) study with alteplase 6-24 hours after onset of acute myocardial infarction. Lancet. 1993; 342: 759-66.

15. Zijlstra F ., Patel A., Jones M., et al. Clinical characteristics and outcome of patients with early (<2 h), intermediate (2-4 h) and late (> 4 h) presentation treated by primary coronary angioplasty or thrombolytic therapy for acute myocardial infarction. Eur Heart J. 2002; 23: 550-7.

16. Weaver W.D., Simes R.J., Betriu A., et al. Comparison of primary coronary angioplasty and intravenous thrombolytic therapy for acute myocardial infarction: a quantitative rewiew. JAMA. 1997; 278: 2093-2098.

17. The Global Use of Strategies to Open Occluded Coronary Arteries in Acute Coronary Syndromes (GUSTO IIb) Angioplasty Substudy Investigators. A clinical trial comparing primary coronary angioplasty with tissue plasminogen activator for acute myocardial infarction. N Engl J Med. 1997; 336: 1621-1628.

18. American Hospital Association. The Annual Survey of Hospitals Database: Documentation for 2000 Data. Chicago, III: American Hospital Association; 2000.

19. Topol E.J. Acute myocardial infarction: thrombolysis. Heart 2000, 83, 122-6.

20. Van de Werf F .J., Ardissino D., Betriu A. et al. The Task Force on the Management of Acute Myocardial Infarction of the European Society of Cardiology.Management of acute myocardial infarction in patients presenting with ST-segment elevation. Eur . Heart. J. 2003; 24: 28-66.

21. Early effects of tissue-type plasminigen activator added to conventional therapy on the culprit coronary lesion in patients presenting with ischemic cardiac pain at rest. Results of the Thrombolysis inMyocardial Ischemia (TIMI IIIa) Trial. Circulation 1993; 87: 38-52.

22. Indications for fibrinolytic therapy in suspected acute myocardial infarction: collaborative overview of early mortality and major morbidity results from all randomized trials of more than 1000 patients. Fibrinolytic Therapy Trialists (FTT) Collaborative Group. Lancet 1994; 343: 311-22.

23. Carbonnier B., Pluta W., De Ferrari G. et al. Evaluation of two weight-adjusted single bolus doses of amediplase to patients with acute myocardial infarction: the 2k2 dose finding trial (ABSTRACT). Circulation 2001; 104: II-538.

24. Van deWerf F .J., Barron H.V., Armsrong P .W., et al. Incidence and predictors of bleeding events after fibrinolytic therapy with fibrin-specific agents: a comparison of TNK-tPA and rt-PA. Eur . Heart J. 2001; 22: 2253-61.

25. Ito H., Tomooka T., Sakai N., et al. Lack of myocardial perfusion immediately after successful thrombolysis. A predictor of poor recovery of left ventricular function in anterior myocardial infarction. Circulation 1992; 85: 1699-705.

26. Johanson P ., Jernberg T., Gunnarsson G., et al. Prognostic value of ST-segment resolution-when and what to measure. Eur Heart J. 2003; 24: 337-45.

27. French J.K., Andrews J., Manda S.O., et al. Early ST-segment recovery , infarct artery blood flow, and long-term outcome after acute myocardial infarction. Am Heart J. 2002; 143: 265-71.

28. Battershill P .E., Benfield P ., Goa K.L. Streptokinase. A review of its pharmacology and therapeutic efficacy in acute myocardial infarction in older patiens. Drugs Aging. 1994; 4: 63-86.

29. Gruppo Italiano per lo Studio della Streptochinasi nell' Infarcto Miocardico (GISSI). Long-term effects of intravenous thrombolysis in acute myocardial infarction: final report of the GISSI study. Lancet 1987; 2: 871-4.

30. Frenzosi M.G., Santoro E., De Vita C., et al. Ten-year follow-up of the first megatrial testing thrombolytic therapy in patients with acute myocardial infarction: results of the Gruppo Italiano per lo Studio della Streptochinasi nell' Infarcto-1 study. Circulation 1998; 98: 2659-65.

31. ISIS-3: a randomized comparison of streptokinase vs tissue plasminogen activator vs anistreplase and of aspirin plus heparin vs aspirin alone among 41,299 cases of suspected acutemyocardial infarction. ISIS-3 (Third International Study of Infarct Survival) Collaborative Group. Lancet 1992; 339: 753-70.

32. Verstraete M., Bernard R., Bory M. et al. Randomized trial of intravenous recombinant tissue-type plasminogen activator vs intravenous streptokinase in acute myocardial infarction. Report from the European Cooperative Study Group for Recombinant tissue-type plasminogen activator . Lancet 1985; 13: 842-848.

33. The TIMI Research Gpoup. The thrombolysis in myocardial infarction (TIMI) trial. Phase I Findings. N. Eng;. J. Med. 1985; 312: 932-936.

34. Chesebro J.H., Knatterud H., Roberts R. et al. Thrombolysis in Myocardial Infarction (TIMI) Trial, Phase 1. A comparison between intravenous tissue plasminogen activator and intravenous streptokinase. Clinical findings through hospital discharge. Circulation 1987; 76: 142-154.

35. Cannon C.P ., McCabe C.H., Diver D.J. et al. Comparison of front-loaded recombinant tissue-type plasminogen activator , anistreplase and combination thrombolytic therapy for acute myocardial infarction: results of the Thrombolysis in Myocardial Infarction (TIMI) 4 trial. Ibid. 1994; 24: 1602- 1610.

36. Шостак Н.А., Константинова Е.В. Применение альтеплазы у больных с острым инфарктом миокарда с подъемом сегмента ST на ЭКГ в типичной клинической практике. Кардиология. 2005; 9: 26-28.

37. Шульман В.А., Радионов В.В., Г оловенкин С.Е. с соавт. Сравнительная оценка эффективности тканевого активатора плазминогена и стрептокиназы в лечении больных острым инфарктом миокарда. Кардиология. 2004; 5: 40-42.

38. Hoffmeister H.M., Kastner C., Szabo S, et al. Fibrin specificity and procoagulant effect related to the kallikrein-contact phase system and to plasmin generation with double-bolus reteplase and front-loaded alteplase thrombolysis in acute myocardial infarction. Am. J. Cardiol. 2000; 86: 263-8.

39. Randomized, double-blind comparison of reteplase double-bolus administration with streptokinase in acute myocardial infarction (INJECT): trial to investigate equivalence. International Joint Efficacy Comparison of Thrombolytics. Lancet 1995; 346: 329-36.

40. The Global Use of Strategies to Open Occluded Coronary Arteries (Gusto III) Investigators. A comparison of reteplase with alteplase for acute myocardial infarction. N. Engl. J. Med. 1997; 337: 1118-1123.

41. Collen D., Stassen J.M.,Yasuda T., et al. Comparative Thrombolytic properties of tissue-type plasminogen activator and of a plasminogen activator inhibitor-1-resistant glycosylation variant, in a combined arterial and venous thrombosis model in the dog. Thromb Hemost 1994,72,98-104.

42. Single-bolus tenecteplase compared with front-loaded alteplase in acute myocardial infarction: the ASSENT-2 double-blind randomized trial. Assessment of the safety and efficacy of a new thrombolytic investigator . Lancet 1999; 354: 716-722.

43. Topol E.J. Gusto V Investigators. 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.

For citation:

Konstantinova E.V., Magnitskyi A.V., Schostak N.A. THROMBOLYTIC THERAPY IN PATIENTS WITH ACUTE MYOCARDIAL INFARCTION. Rational Pharmacotherapy in Cardiology. 2006;2(4):58-62. (In Russ.)

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