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European Heart Journal 2002 23(16):1282-1290; doi:10.1053/euhj.2001.3083
Copyright © 2002 by the European Society of Cardiology.
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Improved reperfusion and clinical outcome with enoxaparin as an adjunct to streptokinase thrombolysis in acute myocardial infarction. The AMI–SK study

M.L. Simoonsa,f1, M. Krzemiñska-Pakulab, A. Alonsoc, S.G. Goodmand, A. Kalie, U. Loosf, F. Gossetg, V. Louerg and F. Bigonzig

a Thorax Centre, Erasmus University Medical Center, Rotterdam, The Netherlands
b Wojewodski Szpital im. Kniaziewicza, Poland
c Puerta de Hierro, Madrid, Spain
d St Michael's Hospital, Division of Cardiology, University of Toronto, Toronto, Canada
e National Institute of Cardiology, Budapest, Hungary
f Knappschafts-Krankenhaus, Recklinghausen, Germany
g Aventis Pharma, Paris, France

revised November 6, 2001; accepted November 7, 2001

Abstract

Aims To establish whether the addition of enoxaparin (a low-molecular-weight heparin) to streptokinase therapy improves early and sustained coronary patency and clinical outcome in patients with evolving myocardial infarction.

Methods and Results A total of 496 patients with acute myocardial infarction treated with streptokinase were randomized to an intravenous bolus (30mg) and subcutaneous injections (1mg.kg–1, twice daily) of enoxaparin (n=253), or placebo (n=243) for 3–8 days. The median duration of treatment in both groups was 5 days. ST-segment resolution at 90min and 180min measured by electrocardiogram was improved in patients receiving enoxaparin. Complete, partial and no ST-segment resolution at 180min was observed in 36%, 44% and 19% in the enoxaparin group vs 25%, 44% and 31% in the placebo group, respectively (P=0·004). Assessment of the primary end-point revealed improved TIMI-3 flow with enoxaparin vs placebo (70% vs 58%, P=0·01). Combined TIMI-2 and -3 flow was also improved (88% vs 72%, P=0·001), as was TIMI frame count (P=0·003). The triple clinical end-point of death, reinfarction and recurrent angina at 30 days was reduced with enoxaparin (13% vs 21%, P=0·03).

Conclusion Streptokinase in combination with enoxaparin is associated with better ST-segment resolution and better angiographic patency at days 5–10, suggesting more effective reperfusion. This was associated with a significant reduction in clinical events, indicating less reocclusion. Copyright 2002 The European Society of Cardiology. Published by Elsevier Science Ltd. All rights reserved.

Key Words: Myocardial infarction, streptokinase, low-molecular-weight heparin, enoxaparin

f1 Correspondence: Prof. dr. M. L. Simoons, Thoraxcentrum, H 560, Erasmus University, Dr. Molewaterplein 40, 3015 GD Rotterdam, the Netherlands.

References

  1. Eur Heart J. 1997;18:1371–1381[Free Full Text]
  2. Eur Heart J. 1996;17:43–63[Free Full Text]
  3. Ryan TJ, Antman EM, Brooks NH. 1999 update: ACC/AHA guidelines for the management of patients with acute myocardial infarction. A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on Management of Acute Myocardial Infarction). J Am Coll Cardiol. 1999;34:890–911[Free Full Text]
  4. De Bono DP, Simoons ML, Tijssen J. 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. Br Heart J. 1992;67:122–128[Abstract/Free Full Text]
  5. Hsia J, Hamilton WP, Kleiman N, Roberts R, Chaitman BR, Ross AM. A comparison between heparin and lowdose aspirin as adjunctive therapy with tissue plasminogen activator for acute myocardial infarction. Heparin-Aspirin Reperfusion Trial (HART) Investigators. N Engl J Med. 1990;323:1433–1437[Abstract]
  6. Bleich SD, Nichols T, Schumacher R. Effect of heparin on coronary arterial patency after thrombolysis with tissue plasminogen activator in acute myocardial infarction. Am J Cardiol. 1990;66:1412–1417[CrossRef][ISI][Medline]
  7. Lancet. 1990;336:65–71[ISI][Medline]
  8. Lancet. 1992;339:753–770[ISI][Medline]
  9. N Engl J Med. 1993;329:673–682[Abstract/Free Full Text]
  10. N Engl J Med. 1993;329:1615–1622[Abstract/Free Full Text]
  11. Brouwer MA, van den Bergh PJPC, Vromans RPJW. Aspirin plus medium intensity coumadin versus aspirin alone in the prevention of reocclusion after successful thrombolysis for suspected acute myocardial infarction: preliminary results of the Apricot-2 trial (Abstr). Circulation. 2000;102:II-600
  12. Noble S, Spencer CM. Enoxaparin. A review of its clinical potential in the management of coronary artery disease. Drugs. 1998;56:259–272[CrossRef][ISI][Medline]
  13. Baird S, McBride S, Trouten TG. LMWH versus unfractionated heparin following thrombolysis in myocardial infarction (Abstr). J Am Coll Cardiol. 1998;31:191a
  14. N Engl J Med. 1985;312:932–936[Medline]
  15. Gibson CM, Cannon CP, Daley WL. TIMI frame count: a quantitative method of assessing coronary artery flow. Circulation. 1996;93:879–888[Abstract/Free Full Text]
  16. van 't Hof A, Liem A, de Boer MJ, Zijlstra F. Clinical value of 12-lead electrocardiogram after successful reperfusion therapy for acute myocardial infarction. Lancet. 1997;350:615–619[CrossRef][ISI][Medline]
  17. Hermens WT, Willems GM, Nijssen KM, Simoons ML. Effect of thrombolytic treatment delay on myocardial infarct size [letter]. Lancet. 1992;340:1297[ISI][Medline]
  18. Bovill EG, Terrin ML, Stump DC. Hemorrhagic events during therapy with recombinant tissue-type plasminogen activator, heparin, and aspirin for acute myocardial infarction. Results of the Thrombolysis in Myocardial Infraction (TIMI), Phase II Trial. Ann Intern Med. 1991;115:256–265[ISI][Medline]
  19. Frostfeldt G, Ahlberg G, Gustafsson G. Low molecular weight heparin (dalteparin) as adjuvant treatment of thrombolysis in acute myocardial infarction—a pilot study: biochemical markers in acute coronary syndromes (BIOMACS II). J Am Coll Cardiol. 1999;33:627–633[Abstract/Free Full Text]
  20. Ronner E, Van Kesteren HA, Zijnen P. Safety and efficacy of eptifibatide vs placebo in patients receiving thrombolytic therapy with streptokinase for acute myocardial infarction. A phase II dose escalation, randomised, double-blind study. Eur Heart J. 2000;21:1530–1536[Abstract/Free Full Text]
  21. Topol EJ, George BS, Kereiakes DJ. A randomized controlled trial of intravenous tissue plasminogen activator and early intravenous heparin in acute myocardial infarction. Circulation. 1989;79:281–286[Abstract/Free Full Text]
  22. Ross AM, Molhoek P, Lendergan C. Randomised comparison of enoxaparin, a low-molecular-weight heparin, with unfractionated heparin adjunctive to recombinant tissue plasminogen activator thrombolysis and aspirin. Second Trial of Heparin and Aspirin Reperfusion Therapy (HART II). Circulation. 2000;104:648–652
  23. Dellborg M, Bergstrand L, Granger C. LMW Heparin (Dalteparin) for improvement of patency after thrombolysis in AMI: A prospective Randomized Multicentre Coronary Angiography Study (Abstr). J Am Coll Cardiol. 2001;37:874–879
  24. Coussement PK, Bassand JP, Convens C. A synthetic factor-Xa inhibitor (ORG31540/SR9017A) as an adjunct to fibrinolysis in acute myocardial infarction. The PENTALYSE study. Eur Heart J. 2001;22:1716–1724[Abstract/Free Full Text]
  25. Lancet. 2001;358:605–613[CrossRef][ISI][Medline]
  26. ASPECT-2 (Anticoagulants in the Secondary prevention of Events in Coronary Thrombosis-2): reports on the effects of aspirin versus aspirin plus coumadin (INR 2.0–2.5) or coumadin (INR 3.0–4.0) on the endpoints death and death/reMI/stroke in past MI patients
  27. Simoons ML, Serruys PW, Brand M vd. Early thrombolysis in acute myocardial infarction: limitation of infarct size and improved survival. J Am Coll Cardiol. 1986;7:717–728[Abstract]
  28. Baardman T, Hermens, Lenderink T. Differential effects of tissue plasminogen activator and streptokinase on infarct size and on rate of enzyme release: influence of early infarct related artery patency. The GUSTO Enzyme Substudy. Eur Heart J. 1996;17:237–246[Abstract/Free Full Text]
  29. Seitz R, Pelzer H, Immel A. Prothrombin activation by thrombolytic agents. Fibrinolysis. 1993;7:109–115[CrossRef][ISI]
  30. Rasmanis G, Versterqvist O, Green K, Edhag O, Henriksson P. Evidence of increased platelet activation after thrombolysis in patient with acute myocardial infarction. Br Heart J. 1992;68:374–376
  31. Leadley RJ Jr, Kasiewski CJ, Bostwick JS. Comparison of enoxaparin, hirulog and heparin as adjunctive antithrombotic therapy during thrombolysis with rtPA in the stenosed canine coronary artery. Thromb Haemost. 1997;78:1278–1285[ISI][Medline]
  32. Lancet. 1996;347:56–58[ISI][Medline]
  33. Cohen M, Demers C, Gurfinkel EP. For the efficacy and safety of subcutaneous enoxaparin in non-Q-wave coronary events study group. A comparison of low molecular weight heparin with unfractionated heparin for unstable coronary artery disease. N Engl J Med. 1997;337:447–452[Abstract/Free Full Text]
  34. Antman E, McCabe CH, Gurfinkel EP. Enoxaparin prevents death and cardiac ischemic events in unstable angina/non-Q wave myocardial infarction: results of the Thrombolysis in Myocardial Infarction (TIMI IIB) trial. Circulation. 1999;100:1593–1601[Abstract/Free Full Text]
  35. Lancet. 1999;354:701–704[CrossRef][ISI][Medline]
  36. Eur Heart J. 1999;20:1553–1562[Abstract/Free Full Text]
  37. Theroux P, Ouimet H, McCans J. Aspirin, heparin, or both to treat acute unstable angina. N Engl J Med. 1988;319:1105–1111[Abstract]

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