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Table of Contents
Vol. 4, No. 3, 2004
Issue release date: July–September 2004
Heart Drug 2004;4:111–118
(DOI:10.1159/000078147)

Low-Molecular-Weight Heparin in Acute Coronary Syndromes

O’Donnell M. · Turpie A.G.G.
Department of Medicine, McMaster University, Hamilton, Ont., Canada

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Abstract

Acute coronary syndrome (ACS) may be divided into two distinct conditions on the basis of the electrographical presence or absence of significant ST-segment elevation. Coronary arterial plaque rupture with subsequent thrombus formation is usually responsible for the development of ACS. A number of antithrombotic therapies have been developed to inhibit key steps in the sequential process of thrombus formation. Thrombin generation is of critical importance in the creation of intracoronary thrombosis. Heparins, in therapeutic doses, reduce the risk of death and myocardial infarction by about 50% in aspirin-treated patients presenting with ACS with non-ST-segment elevation. Low-molecular-weight heparin (LMWH) primarily targets the inhibition of factor Xa (and to a lesser extent thrombin) by binding with antithrombin. A number of well-designed, large randomized controlled trials have shown that LMWHs have at least comparable efficacy and safety to unfractionated heparin, but their superior practical advantages have made them a mainstay therapy in the treatment of ACS with non-ST-segment elevation. More recently, the role of LMWH in the treatment of ACS with ST elevation has been evaluated in a large randomized trial.



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References

  1. Hamm CW, Bertrand M, Braunwald E: Acute coronary syndrome without ST elevation: Implementation of new guidelines. Lancet 2002;358:1533–1538.
  2. Collins R, MacMahon S, Flather M, Baigent C, Remvig L, Mortensen S, Appleby P, Godwin J, Yusuf S, Peto R: Clinical effects of anticoagulant therapy in suspected acute myocardial infarction: Systematic overview of randomised trials. BMJ 1996;313:652–659.
  3. The TIMI IIIB Investigators: 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;89:1545–1556.
  4. Weitz JI: Activation of blood coagulation by plaque rupture: Mechanisms and prevention. Am J Cardiol 1995;75:23–25.
  5. Fuster V, Badimon L, Badimon JJ, Chesebro JH: The pathogenesis of coronary artery disease and the acute coronary syndromes. N Engl J Med 1992;326:242–250.
  6. Ardissino D, Merlini PA, Ariens R, Coppola R, Bramucci E, Mannucci PM: Tissue-factor antigen and activity in human coronary atherosclerotic plaques. Lancet 1997;349:769–771.
  7. Davies MJ, Thomas AC: Plaque fissuring: The cause of acute myocardial infarction, sudden ischemic death, and crescendo angina. Br Heart J 1985;53:363–373.
  8. Toschi V, Gallo R, Lettino M, Fallon JT, Gertz SD, Fernandez-Ortiz A, Chesebro JH, Badimon L, Nemerson Y, Fuster V, Badimon JJ: Tissue factor modulates the thrombogenicity of human atherosclerotic plaques. Circulation 1997;95:594–599.
  9. Weitz JL: Low molecular weight heparins. N Engl J Med 1997;337:688–689.
  10. Eikelboom JW, Anand SS, Malmberg K, Weitz JI, Ginsberg JS, Yusuf S: Unfractionated heparin and low-molecular-weight heparin in acute coronary syndrome without ST elevation: A meta-analysis. Lancet 2000;355:1936–1942.
  11. Assessment of the Safety and Efficacy of a New Thrombolytic Regimen (ASSENT)-3 Investigators: Efficacy and safety of tenecteplase in combination with enoxaparin, abciximab, or unfractionated heparin: the ASSENT-3 randomised trial in acute myocardial infarction. Lancet 2001;358:605–613.
  12. Fareed J, Jeske W, Hoppensteadt D, Clarizio R, Walenga JM: Are the available low-molecular-weight heparin preparations the same? Semin Thromb Hemost 1996;22(suppl 1):77–91.

    External Resources

  13. Hoppensteadt DA, Jeske W, Fareed J, Bermes EW Jr: The role of tissue factor pathway inhibitor in the mediation of the antithrombotic actions of heparin and low-molecular-weight heparin. Blood Coagul Fibrinolysis 1995;6(suppl 1):S57–S64.

    External Resources

  14. Hirsh J, Warkentin TE, Shaughnessy SG, Anand SS, Halperin JL, Raschke R, Granger C, Ohman EM, Dalen JE: Heparin and low-molecular-weight heparin: Mechanisms of action, pharmacokinetics, dosing, monitoring, efficacy, and safety. Chest 2001;119(1 suppl):64S–94S.

    External Resources

  15. Nieuwenhuis HK, Albada J, Banga JD, Sixma JJ: Identification of risk factors for bleeding during treatment of acute venous thromboembolism with heparin or low molecular weight heparin. Blood 1991;78:2337–2343.
  16. Klein W, Buchwald A, Hillis WS, Monrad S, Sanz G, Turpie AG, van der Meer J, Olaisson E, Undeland S, Ludwig K: Comparison of low-molecular-weight heparin with unfractionated heparin acutely and with placebo for 6 weeks in the management of unstable coronary artery disease: Fragmin in Unstable Coronary Artery Disease Study (FRIC). Circulation 1997;96:61–68.
  17. Cohen M, Demers C, Gurfinkel EP, Turpie AG, Fromell GJ, Goodman S, Langer A, Califf RM, Fox KA, Premmereur J, Bigonzi F: A comparison of low-molecular weight heparin with unfractionated heparin for unstable coronary artery disease. Efficacy and Safety of Subcutaneous Enoxaparin in Non-Q-Wave Coronary Events Study Group. N Engl J Med 1997;337:447–452.
  18. Antman EM, McCabe CH, Gurfinkel EP, Turpie AG, Bernink PJ, Salein D, Bayes De Luna A, Fox K, Lablanche JM, Radley D, Premmereur J, Braunwald E: Enoxaparin prevents death and cardiac ischemic events in unstable angina/non-Q-wave myocardial infarction: Results of the Thrombolysis in Myocardial Infarction (TIMI) 11B Trial. Circulation 1999;100:1593–1601.
  19. Bendz B, Hansen JB, Andersen TO, Ostergaard P, Sandset PM: Partial depletion of tissue factor pathway inhibitor during subcutaneous administration of unfractionated heparin, but not with two low molecular weight heparins. Br J Haematol 1999;107:756–762.
  20. Lewis HD Jr, Davis JW, Archibald DG, Steinke WE, Smitherman TC, Doherty JE 3rd, Schnaper HW, LeWinter MM, Linares E, Pouget JM, Sabharwal SC, Chesler E, DeMots H: Protective effects of aspirin against acute myocardial infarction and death in men with unstable angina. Results of a Veterans Administration Cooperative Study. N Engl J Med 1983;309:396–403.
  21. Oler A, Whooley MA, Oler J, Grady D: Adding heparin to aspirin reduces the incidence of myocardial infarction and death in patients with unstable angina: A meta-analysis. JAMA 1996;276:811–815.
  22. Low-molecular-weight heparin during instability in coronary artery disease. Fragmin during Instability in Coronary Artery Disease (FRISC) Study Group. Lancet 1996;347:561–568.
  23. Merlini PA, Bauer KA, Oltrona L, Ardissino D, Cattaneo M, Belli C, Mannucci PM, Rosenberg RD: Persistent activation of coagulation mechanism in unstable angina and myocardial infarction. Circulation 1994;90:61–68.
  24. 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;354:701–704.
  25. FRAXIS Study Group: Comparison of two treatment durations (6 days and 14 days) of a low molecular weight heparin with a 6-day treatment of unfractionated heparin in the initial management of unstable angina or non-Q wave myocardial infarction: FRAXIS. (FRAxiparine in Ischaemic Syndrome). Eur Heart J 1999;20:1553–1562.
  26. Goodman SG, Cohen M, Bigonzi F, Gurfinkel EP, Radley DR, Le Iouer V, Fromell GJ, Demers C, Turpie AG, Califf RM, Fox KA, Langer A: Randomized trial of low molecular weight heparin (enoxaparin) versus unfractionated heparin for unstable coronary artery disease: One-year results of the ESSENCE Study. Efficacy and Safety of Subcutaneous Enoxaparin in Non-Q Wave Coronary Events. J Am Coll Cardiol 2000;36:693–698.
  27. Antman EM, Cohen M, Radley D, McCabe C, Rush J, Premmereur J, Braunwald E, for the TIMI 11B (Thrombolysis in Myocardial Infarction) and ESSENCE (Efficacy and Safety of Subcutaneous Enoxaparin in Non-Q-Wave Coronary Events) Investigators: 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.
  28. Cohen M, Turpie AG: Management of unstable angina and myocardial infarction. Lancet 2000;356:1193–1194.
  29. Lee TH, Goldman L: Evaluation of the patient with acute chest pain. N Engl J Med 2000;342:1187–1189.
  30. Antman EM, Louwerenburg HW, Baars HF, Wesdorp JC, Hamer B, Bassand JP, Bigonzi F, Pisapia G, Gibson CM, Heidbuchel H, Braunwald E, Van de Werf F: Enoxaparin as adjunctive antithrombin therapy for ST-elevation myocardial infarction: results of the ENTIRE-Thrombolysis in Myocardial Infarction (TIMI) 23 Trial. Circulation 2002;105:1642–1649.
  31. Kereiakes DJ, Montalescot G, Antman EM, Cohen M, Darius H, Ferguson JJ, Grines C, Karsch KR, Kleiman NS, Moliterno DJ, Steg PG, Teirstein P, Van de Werf F, Wallentin L: 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.
  32. Collet JP, Montalescot G, Lison L, Choussat R, Ankri A, Drobinski G, Sotirov I, Thomas D: Percutaneous coronary intervention after subcutaneous enoxaparin pretreatment in patients with unstable angina pectoris. Circulation 2001;103:658–663.
  33. Batchelor WB, Mahaffey KW, Berger PB, Deutsch E, Meier S, Hasselblad V, Fry ET, Teirstein PS, Ross AM, Binanay CA, Zidar JP; ATLAST Trial Investigators: A randomized, placebo-controlled trial of enoxaparin after high-risk coronary stenting: The ATLAST trial. J Am Coll Cardiol 2001;38:1608–1613.


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