Semin Vasc Med 2003; 03(2): 139-146
DOI: 10.1055/s-2003-40672
Copyright © 2003 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA. Tel.: +1(212) 584-4662

The Present and Future of Heparin, Low Molecular Weight Heparins, Pentasaccharide, and Hirudin for Venous Thromboembolism and Acute Coronary Syndromes

Sylvia Haas
  • Klinikum rechts der Isar, Institut für Experimentelle Onkologie und Therapieforschung, Munich, Germany
Further Information

Publication History

Publication Date:
18 July 2003 (online)

ABSTRACT

Due to their favorable pharmacologic properties and beneficial clinical effects, low molecular weight heparins (LMWHs) have become the standard of care in the prevention and treatment of venous thromboembolism and have also been extensively studied in the treatment of acute coronary syndromes. Pentasaccharide is the first of a new class of synthetic antithrombotics and has been shown to be superior to LMWH in preventing deep vein thrombosis. Hirudin is the most potent direct thrombin inhibitor and has provided superior antithrombotic efficacy when compared with LMWH. In acute coronary syndromes, however, the antithrombotic activity of hirudin has been compromised by a significant increase in major hemorrhage.

REFERENCES

  • 1 Rosenberg R D, Damu P S. The purification and mechanism of action of human antithrombin-heparin cofactor.  J Biol Chem . 1973;  248 6490-6505
  • 2 Lam L H, Silbert J E, Rosenberg R D. The separation of active and inactive forms of heparin.  Biochem Biophys Res Commun . 1976;  69 570-577
  • 3 Lindahl U, Backstrom G, Thunberg L. The antithrombin-binding sequence in heparin: identification of an essential 6-O-sulfate group.  J Biol Chem . 1983;  25 9826-9830
  • 4 Gallo R, Chesebro J H, Badimon J J. Treatment of unstable angina: role of antithrombotic therapy.  Thromb Res . 1999;  95 V15-V31
  • 5 Jeske W, Fareed J. In vitro studies on the biochemistry and pharmacology of low molecular weight heparin.  Semin Thromb Hemost . 1999;  25 27-34
  • 6 Olson S T, Björk I, Sheffer R, Craig P A, Shore J D, Choay J. Role of the antithrombin-binding pentasaccharide in heparin acceleration of antithrombin-proteinase reactions: resolution of the antithrombin conformational change contribution to heparin rate enhancement.  J Biol Chem . 1992;  267 12528-12538
  • 7 Haas S. Prevention of venous thromboembolism: recommendations based on the International Consensus and the American College of Chest Physicians Sixth Consensus Conference on antithrombotic therapy.  Clin Appl Thromb Hemost . 2001;  7 171-177
  • 8 Haas S. Treatment of deep venous thrombosis and pulmonary embolism.  Med Clin North Am . 1998;  82 495-510
  • 9 Gurfinkel E P, Manos E J, Mejail R I. Low-molecular-weight heparin versus regular heparin or aspirin in the treatment of unstable angina.  J Am Coll Cardiol . 1994;  24 39-45
  • 10 Fragmin During Instability in Coronary Artery Disease (FRISC) Study Group. Low-molecular-weight heparin during instability in coronary artery disease. Lancet 1996 347: 561-568
  • 11 Swahn E, Wallentin L, for the FRISC Study Group. Low-molecular-weight heparin (Fragmin) during instability in coronary artery disease (FRISC).  Am J Cardiol . 1997;  80 (suppl 5A) 25E-29E
  • 12 Klein W, Buchwald A, Hillis S E, for the FRIC Investigators. 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
  • 13 Cohen M, Demers C, Gurfinkel E P. A comparison of low molecular-weight heparin weight unfractionated heparin for unstable coronary artery disease.  N Engl J Med . 1997;  337 447-452
  • 14 Goodman S, Bigonzi F, Radley D, Le Louer V, Gosset F, Cohen M, for the ESSENCE Group. One-year follow-up of the ESSENCE trial (enoxaparin versus heparin in unstable angina and non-Q-wave myocardial infarction (abstract).  Eur Heart J . 1998;  50 P477
  • 15 Antman E M, McCabe C H, Gurfinkel E P, for the TIMI 11B Investigators. 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
  • 16 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
  • 17 Zidar J P. Low-molecular weight heparins in coronary stenting (the ENTICES trial). Enoxaparin and ticolpidine after elective stenting.  Am J Cardiol . 1998;  82 29L-32L
  • 18 The 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
  • 19 Turpie A GG, Gallus A S, Hoek J A. A synthetic pentasaccharide for the prevention of deep-vein thrombosis after total hip replacement.  N Engl J Med . 2001;  344 619-625
  • 20 Lassen M R, Bauer K A, Eriksson B I, Turpie A G. for the European Pentasaccharide Hip Elective Surgery Study (EPHESUS) Steering Committee. Postoperative fondaparinux versus preoperative enoxyparin for prevention of venous thromboembolism in elective hip-replacement surgery: a randomised double-blind comparison.  Lancet . 2002;  359 1715-1720
  • 21 Turpie A G, Bauer K A, Eriksson B I, Lassen M R, for the PENTATHLON 2000 Study Steering Committee. Postoperative fondaparinux versus postoperative enoxyparin for prevention of venous thromboembolism after elective hip-replacement surgery: a randomised double-blind trial.  Lancet . 2002;  359 1721-1726
  • 22 Bauer K A, Eriksson B A, Lassen M R, Turpie A G. for the Steering Committee of the Pentasaccharide in Major Knee Surgery Study (PENTAMAKS). Fondaparinux compared with enoxyparin for the prevention of venous thromboembolism after elective knee surgery.  N Engl J Med . 2001;  345 1305-1310
  • 23 Eriksson B I, Bauer K A, Lassen M R, Turpie A G. for the Steering Committee of the Pentasaccharide in Hip-Fracture Surgery Study (Penthifra). Fondaparinux compared with enoxyparin for the prevention of venous thromboembolism after hip-fracture surgery.  N Engl J Med . 2001;  345 1298-1304
  • 24 Turpie A G, Bauer K A, Eriksson B I, Lassen M R. Fondaparinux vs enocyparin for prevention of venous thromboembolism in major orthopedic surgery: a meta-analysis of 4 randomized double-blind studies.  Arch Intern Med . 2002;  162 1833-1840
  • 25 Topol E J, Fuster V, Harrington D J. Recombinant hirudin for unstable angina pectoris: a multicentre, randomized, angiographic trial.  Circulation . 1994;  89 1557-1559
  • 26 GUSTO IIb Investigators. A comparison of recombinant hirudin with heparin for the treatment of acute coronary syndromes N Engl J Med .  1996;  335 775-782
  • 27 Organization to Assess Strategies for Ischemic Syndromes (OASIS) Investigators. Comparison of the effects of two doses of recombinant hirudin compared with heparin in patients with acute myocardial ischemia without ST elevation: a pilot study. Circulation 1997 96: 769-777
  • 28 OASIS-2 Investigators. Effects of recombinant hirudin (lepirudin) compared with heparin on death, myocardial infarction, refractory angina, and revascularisation procedures in patients with acute myocardial ischaemia without ST elevation: a randomised trial.  Lancet . 1999;  353 429-438
  • 29 Eriksson B I, Wille-Jörgensen P, Kälebo P, Mouret P. A comparison of recombinant hirudin with a low-molecular weight heparin to prevent thromboembolic complications after total hip replacement.  N Engl J Med . 1997;  337 1329-1335
  • 30 Moia M, Schiele F, Walker. Treatment of acute deep vein thrombosis (DVT) by subcutaneous r-hirudin (HBW 023): a multi-centre study.  Thromb Haemost . 1995;  83 1456
  • 31 Parent F, Bridey F, Dreyfus M. Treatment of severe venous thrombo-embolism with intravenous hirudin (HBW 023): an open pilot study.  Thromb Haemost . 1993;  70 386
  • 32 Schiele F, Vuillemenot A, Kramarz P. A pilot study of subcutaneous recombinant hirudin (HBW 023) in the treatment of deep vein thrombosis.  Thromb Haemost . 1994;  71 558
    >