Semin Vasc Med 2003; 03(4): 391-402
DOI: 10.1055/s-2004-817703

Copyright © 2003 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA. Tel.: +1(212) 584-4662

Low-Molecular-Weight Heparins for the Treatment of Acute Coronary Syndromes

Graham C. Wong1 , Robert P. Giugliano2
  • 1Vancouver General Hospital, University of British Columbia, Vancouver, BC, Canada
  • 2Brigham and Women's Hospital, Harvard Medical School, Boston, MA
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03. Februar 2004 (online)


Low-molecular-weight heparins (LMWHs) possess several advantages over unfractionated heparin (UFH) for the treatment of acute coronary syndromes (ACSs). Already a class I indication for the treatment of unstable angina/non-ST elevation myocardial infarction (UA/NSTEMI), LMWHs also show promise in the setting of ST elevation myocardial infarction (STEMI) and percutaneous coronary intervention (PCI). Moreover, a growing body of evidence has demonstrated equivalent safety of LMWH with concomitant use of glycoprotein IIb/IIIa inhibitors. Larger clinical studies are needed to confirm the safety and efficacy of LMWH as an antithrombin for the treatment across the spectrum of ACS.


  • 1 Braunwald E, Antman E M, Beasley J W. et al .ACC/AHA guideline update for the management of patients with unstable angina and non-ST-segment elevation myocardial infarction: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee of the Management of Patients With Unstable Angina). 2002. Available at unstable.pdf
  • 2 Ryan T J, Antman E M, Brooks N H. et al . 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
  • 3 Hansen J B, Sandset P M, Huseby K R. et al . Differential effect of unfractionated heparin and low molecular weight heparin on intravascular tissue factor pathway inhibitor: evidence for a difference in antithrombotic action.  Br J Haematol . 1998;  101 638-646
  • 4 Montalescot G, Collet J P, Lison L. et al . Effects of various anticoagulant treatments on von Willebrand factor release in unstable angina.  J Am Coll Cardiol . 2000;  36 110-114
  • 5 Morrow D A, Rifai N, Bigonzi F. et al . Enoxaparin attenuates the rise in von Willebrand factor in patients with ST-segment elevation myocardial infarction treated with fibrinolysis: results from ENTIRE-TIMI 23.  Eur Heart J . 2002;  23(abstr suppl) 506
  • 6 Duplaga B A, Rivers C W, Nutescu E. Dosing and monitoring of low-molecular-weight heparins in special populations.  Pharmacotherapy . 2001;  21 218-234
  • 7 Michalis L K, Katsouras C, Papamichael N. et al . Enoxaparin versus tinzaparin in non-ST-segment elevation acute coronary syndromes: the EVET trial.  Am Heart J . 2003;  146 304-310
  • 8 The FRISC Study Group. 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
  • 9 Gurfinkel E P, Manos E J, Mejail R I. et al . Low molecular weight heparin versus regular heparin or aspirin in the treatment of unstable angina and silent ischemia.  J Am Coll Cardiol . 1995;  26 313-318
  • 10 Klein W, Buchwald A, Hillis S E. et al . 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
  • 11 Cohen M, Demers C, Gurfinkel E P. et al . 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
  • 12 Antman E M, McCabe C H, Gurfinkel E P. et al . 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
  • 13 The FRAX IS Investigators. 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
  • 14 The FRISC II Investigators. Long-term low-molecular-mass heparin in unstable coronary-artery disease: FRISC II prospective randomised multicentre study.  Lancet . 1999;  354 701-707
  • 15 Antman E M, Cohen M, Radley D. et al . 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
  • 16 Kaul S, Shah P K. Low molecular weight heparin in acute coronary syndrome: evidence for superior or equivalent efficacy compared with unfractionated heparin?.  J Am Coll Cardiol . 2000;  35 1699-1712
  • 17 Eikelboom J W, Anand S S, Malmberg K, Weitz J I, Ginsberg J S, Yusuf S. Unfractionated heparin and low-molecular-weight heparin in acute coronary syndrome without ST elevation: a meta-analysis.  Lancet . 2000;  355 1936-1942
  • 18 Lindahl B, Venge P, Wallentin L. Troponin T identifies patients with unstable coronary artery disease who benefit from long-term antithrombotic protection. Fragmin in Unstable Coronary Artery Disease (FRISC) Study Group.  J Am Coll Cardiol . 1997;  29 43-48
  • 19 Lindahl B, Diderholm E, Lagerqvist B, Venge P, Wallentin L. Mechanisms behind the prognostic value of troponin T in unstable coronary artery disease: a FRISC II substudy.  J Am Coll Cardiol . 2001;  38 979-986
  • 20 Antman E M, Cohen M, Bernink P J. et al . The TIMI risk score for unstable angina/non-ST elevation MI: a method for prognostication and therapeutic decision making.  JAMA . 2000;  284 835-842
  • 21 Fox K, Antman E, Cohen M, Bigonzi F. Comparison of enoxaparin versus unfractionated heparin in patients with unstable angina pectoris/non-ST-segment elevation acute myocardial infarction having subsequent percutaneous coronary intervention.  Am J Cardiol . 2002;  90 477-482
  • 22 Merlini P A, Ardissino D, Rosenberg R D. et al . In vivo thrombin generation and activity during and after intravenous infusion of heparin or recombinant hirudin in patients with unstable angina pectoris.  Arterioscler Thromb Vasc Biol . 2000;  20 2162-2166
  • 23 Antman E M, Cohen M, McCabe C, Goodman S G, Murphy S A, Braunwald E. Enoxaparin is superior to unfractionated heparin for preventing clinical events at 1-year follow-up of TIMI 11B and ESSENCE.  Eur Heart J . 2002;  23 308-314
  • 24 Seitz R, Pelzer H, Immel A. Prothrombin activation by thrombolytic agents.  Fibrinolysis . 1993;  7 109-115
  • 25 Granger C B, Becker R, Tracy R P. et al . Thrombin generation, inhibition and clinical outcomes in patients with acute myocardial infarction treated with thrombolytic therapy and heparin: results from the GUSTO-I Trial GUSTO-I Hemostasis Substudy Group. Global Utilization of Streptokinase and TPA for Occluded Coronary Arteries.  J Am Coll Cardiol . 1998;  31 497-505
  • 26 Collins R, MacMahon S, Flather M. et al . Clinical effects of anticoagulant therapy in suspected acute myocardial infarction: systematic overview of randomised trials.  BMJ . 1996;  313 652-659
  • 27 Granger C B, Hirsch J, Califf R M. et al . Activated partial thromboplastin time and outcome after thrombolytic therapy for acute myocardial infarction: results from the GUSTO-I trial.  Circulation . 1996;  93 870-878
  • 28 Giugliano R P, McCabe C H, Antman E M. et al . Lower-dose heparin with fibrinolysis is associated with lower rates of intracranial hemorrhage.  Am Heart J . 2001;  141 742-750
  • 29 Kontny F, Dale J, Abildgaard U, Pedersen T R. Randomized trial of low molecular weight heparin (dalteparin) in prevention of left ventricular thrombus formation and arterial embolism after acute anterior myocardial infarction: the Fragmin in Acute Myocardial Infarction (FRAMI) Study.  J Am Coll Cardiol . 1997;  30 962-969
  • 30 Frostfeldt G, Ahlberg G, Gustafsson G. et al . 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
  • 31 Tatu-Chitoiu G, Tatu-Chitoiu A, Bumbu A, Teodorescu C, Capraru P, Guran M. et al . Accelerated streptokinase and enoxaparine-a new thrombolytic regimen in acute myocardial infarction (the ASENOX study).  Eur Heart J . 2000;  21(abstr suppl) 177
  • 32 Wallentin L, Dellborg D M, Lindahl B, Nilsson T, Pehrsson K, Swahn E. The low-molecular-weight heparin dalteparin as adjuvant therapy in acute myocardial infarction: the ASSENT PLUS study.  Clin Cardiol . 2001;  24(3 suppl) I12-I14
  • 33 The 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
  • 34 Ross A M, Molhoek P, Lundergan C. et al . Randomized 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 . 2001;  104 648-652
  • 35 Antman E M, Louwerenburg H W, Baars H F. et al . 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
  • 36 Baird S H, Menown I B, McBride S J, Trouton T G, Wilson C. Randomized comparison of enoxaparin with unfractionated heparin following fibrinolytic therapy for acute myocardial infarction.  Eur Heart J . 2002;  23 627-632
  • 37 Wallentin L, Goldstein P, Armstrong P W. et al . Efficacy and safety of tenecteplase in combination with the low molecular weight heparin enoxaparin or unfractionated heparin in the prehospital setting. Assessment of the safety and efficacy of a new thrombolytic regiment (ASSENT)-3 PLUS Randomized trial in accute myocardial infarction.  Circulation . 2003;  108 135-142
  • 38 Simoons M, Krzeminska-Pakula M, Alonso A. et al . Improved reperfusion and clinical outcome with enoxaparin as an adjunct to streptokinase thrombolysis in acute myocardial infarction. The AMI-SK study.  Eur Heart J . 2002;  23 1282
  • 39 Cohen M, Theroux P, Weber S. et al . Combination therapy with tirofiban and enoxaparin in acute coronary syndromes.  Int J Cardiol . 1999;  71 273-281
  • 40 Ferguson J J. The use of enoxaparin and IIb/IIIa antagonists in acute coronary syndromes; including PCI: final results of the NICE 3 study.  J Am Coll Cardiol . 2001;  37 (suppl A) 365A
  • 41 Cohen M, Theroux P, Borzak S. et al . Randomized double-blind safety study of enoxaparin versus unfractionated heparin in patients with non-ST-segment elevation acute coronary syndromes treated with tirofiban and aspirin: the ACUTE II study. The Antithrombotic Combination Using Tirofiban and Enoxaparin.  Am Heart J . 2002;  144 470-477
  • 42 James S, Armstrong P, Califf R. et al . Safety and efficacy of abciximab combined with dalteparin in treatment of acute coronary syndromes.  Eur Heart J . 2002;  23 1538-1545
  • 43 Goodman S. Integrilin and Enoxaparin Randomized assessment of Acute Coronary Syndromes Treatment (INTERACT). In: American College of Cardiology 51st Annual Scientific Session; 2002; Atlanta, GA; 2002
  • 44 Mukherjee D, Mahaffey K W, Moliterno D J. et al . Promise of combined low-molecular-weight heparin and platelet glycoprotein IIb/IIIa inhibition: results from Platelet IIb/IIIa Antagonist for the Reduction of Acute coronary syndrome events in a Global Organization Network B (PARAGON B).  Am Heart J . 2002;  144 995-1002
  • 45 Boersma E, Harrington R A, Moliterno D J. 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
  • 46 Cohen M. The Treatment with Enoxaparin and Tirofiban in Acute Myocardial Infarction (TETAMI) Study. In: American Heart Association 75th Scientific Sessions; 2002; Chicago, IL; 2002
  • 47 Bhatt D L, Lee B I, Casterella P J. et al . Safety of concomitant therapy with eptifibatide and enoxaparin in patients undergoing percutaneous coronary intervention: results of the Coronary Revascularization Using Integrilin and Single bolus Enoxaparin Study.  J Am Coll Cardiol . 2003;  41 20-25
  • 48 Choussat R, Montalescot G, Collet J P. et al . A unique, low dose of intravenous enoxaparin in elective percutaneous coronary intervention.  J Am Coll Cardiol . 2002;  40 1943-1950
  • 49 Kereiakes D J, Kleiman N S, Fry E. et al . Dalteparin in combination with abciximab during percutaneous coronary intervention.  Am Heart J . 2001;  141 348-352
  • 50 Kereiakes D J, Grines C, Fry E. et al . Enoxaparin and abciximab adjunctive pharmacotherapy during percutaneous coronary intervention.  J Invasive Cardiol . 2001;  13 272-278
  • 51 Collet J P, Montalescot G, Lison L. et al . Percutaneous coronary intervention after subcutaneous enoxaparin pretreatment in patients with unstable angina pectoris.  Circulation . 2001;  103 658-663
  • 52 Martin J L, Fry E TA, Serano A. Pharmacokinetic study of enoxaparin in patients undergoing coronary intervention after treatment with subcutaneous enoxaparin in acute coronary syndromes. The PEPCI Study.  Eur Heart J . 2001;  22(abstr suppl) 14
  • 53 Karsch K R, Preisack M B, Baildon R. et al . Low molecular weight heparin (reviparin) in percutaneous transluminal coronary angioplasty. Results of a randomized, double-blind, unfractionated heparin and placebo-controlled, multicenter trial (REDUCE trial). Reduction of Restenosis After PTCA, Early Administration of Reviparin in a Double-Blind Unfractionated Heparin and Placebo-Controlled Evaluation.  J Am Coll Cardiol . 1996;  28 1437-1443
  • 54 Rabah M M, Premmereur J, Graham M. et al . Usefulness of intravenous enoxaparin for percutaneous coronary intervention in stable angina pectoris.  Am J Cardiol . 1999;  84 1391-1395
  • 55 The FRISC II Investigators. Invasive compared with non-invasive treatment in unstable coronary-artery disease: FRISC II prospective randomised multicentre study. FRagmin and Fast Revascularisation during InStability in Coronary artery disease Investigators.  Lancet . 1999;  354 708-715
  • 56 Blazing M A, De Lemos A J, Dyke C K, Califf R M, Bilheimer D, Braunwald E. The A-to-Z Trial: methods and rationale for a single trial investigating combined use of low-molecular-weight heparin with the glycoprotein IIb/IIIa inhibitor tirofiban and defining the efficacy of early aggressive simvastatin therapy.  Am Heart J . 2001;  142 211-217
  • 57 The SYNERGY Executive Committee. The SYNERGY trial: study design and rationale.  Am Heart J . 2002;  143 952-960