Skip to main content
SpringerLink
Log in

Low molecular weight heparins and coronary artery disease

  • Published:
Current Cardiology Reports Aims and scope Submit manuscript

Abstract

Coronary artery disease encompasses a wide spectrum of conditions including silent ischemia, exertional angina, unstable angina, and myocardial infarction. Acute coronary syndromes (unstable angina and myocardial infarction) are caused by the rupture of an atherosclerotic plaque, platelet activation, and fibrin deposition resulting in thrombosis. Aspirin and unfractionated heparin (UFH) have traditionally been the treatment of choice in patients with acute coronary syndromes; however, low molecular weight heparins (LMWHs) offer potential advantages over UFH. Available evidence indicates that LMWH is superior to UFH in reducing ischemic events or death in the acute phase of unstable angina or non-Q-wave myocardial infarction. Long-term therapy with lower doses of LMWH may not offer any advantage to aspirin in the prevention of coronary events or death. Major bleeding complications are similar for LMWH and UFH although minor bleeding complications are more common with LMWH, primarily due to injection-site hematomas. Finally, use of LMWH appears to be costeffective compared with UFH. The available evidence supports improved clinical outcomes, favorable safety profile, and cost savings associated with LMWH use in the management of unstable angina and non-Q-wave myocardial infarction and should be favored over UFH.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References and Recommended Reading

  1. Theroux P, Fuster V: Acute coronary syndromes. Unstable angina and non-Q-wave myocardial infarction. Circulation 1998, 97:1195–1206.

    PubMed  CAS  Google Scholar 

  2. 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.

    Article  PubMed  CAS  Google Scholar 

  3. Theroux P, Ouimet H, McCans J, et al.: Aspirin, heparin, or both to treat acute unstable angina. N Engl J Med 1988, 319:1105–1111.

    Article  PubMed  CAS  Google Scholar 

  4. The RISC Group: Risk of myocardial infarction and death during treatment with low dose aspirin and intravenous heparin in men with unstable coronary artery disease. Lancet 1990, 336 827–830.

    Article  Google Scholar 

  5. Theroux P, Waters D, Qiu S, et al.: Aspirin versus heparin to prevent myocardial infarction during the acute phase of unstable angina. Circulation 1993, 88(part 1):2045–2048.

    PubMed  CAS  Google Scholar 

  6. Cohen M, Adams PC, Parry G, et al.: Combination antithrombotic therapy in unstable rest angina and non-Q-wave infarction in nonprior aspirin users: primary end points analysis from the ATACS trial. Circulation 1994, 89:81–88.

    PubMed  CAS  Google Scholar 

  7. Neri Serneri GG, Modesti PA, Gensini GF, et al.: Randomized comparison of subcutaneous heparin, intravenous heparin and aspirin in unstable angina. Lancet 1995 345:1201–1204.

    Article  Google Scholar 

  8. Theroux P, Waters D, Lam J, et al.: Reactivation of unstable angina after the discontinuation of heparin. N Engl J Med 1992, 327:141–145.

    Article  PubMed  CAS  Google Scholar 

  9. Holdright D, Patel D, Cunningham D, et al.: Comparison of the effect of heparin and aspirin versus aspirin alone on transient myocardial ischemia and in-hospital prognosis in patients with unstable angina. J Am Coll Cardiol 1994, 24:39–45.

    Article  PubMed  CAS  Google Scholar 

  10. Cairns JA, Gent M, Singer J, et al.: Aspirin, sulfinpyrazone, or both in unstable angina: results of a Canadian multicenter trial. N Engl J Med 1985, 313:1369–1375.

    Article  PubMed  CAS  Google Scholar 

  11. Lewis H Jr, Davis JW, Archibald DG, et al.: 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.

    Article  PubMed  Google Scholar 

  12. 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.

    Article  PubMed  CAS  Google Scholar 

  13. Cairns JA, Theroux P, Lewis HD Jr, et al.: Antithrombotic agents in coronary artery disease. Chest 1998, 114 (suppl):611S-633S.

    PubMed  CAS  Google Scholar 

  14. Leizororovicz A, Simonneau G, Decousis H, Boissel JP: Comparison of efficacy and safety of low-molecularweight heparins and unfractionated heparin in initial treatment of venous thrombosis: a meta-analysis. BMJ 1994, 309:299–304.

    Google Scholar 

  15. Lensing AWA, Prins MH, Davidson BL, Hirsch J: Treatment of deep-vein thrombosis with low molecular-weight heparins: a meta-analysis. Arch Intern Med 1995, 155:601–607.

    Article  PubMed  CAS  Google Scholar 

  16. The Columbus Investigators: Low-molecular weight heparin in the treatment of patients with venous thromboembolism. N Eng J Med 1997, 337:657–662.

    Article  Google Scholar 

  17. Hirsh J, Levine MN: Low molecular weight heparin. Blood 1992, 79 1–17.

    PubMed  CAS  Google Scholar 

  18. Weitz JI: Low-molecular-weight heparins. N Engl J Med 1997, 337:688–698.

    Article  PubMed  CAS  Google Scholar 

  19. Beguin S, Mardiguian J, Lindhout T, Hemker HC: The mode of action of low molecular weight heparin preparation (PK 10169) and two of its major components on thrombin generation in plasma. Thromb Haemost 1989, 61:30–34.

    PubMed  CAS  Google Scholar 

  20. Barrowcliffe TW, Merton RE, Havercroft SJ, et al.: Low-affinit heparin potentiates the action of high-affinity heparin oligosaccharides. Thromb Res 1984, 34:125–133.

    Article  PubMed  CAS  Google Scholar 

  21. Young E, Wells P, Holloway S, et al.: Ex-vivo and in-vitro evidence that low-molecular weight heparins exhibit less binding to plasma proteins than unfractionated heparin. Thromb Haemost 1994, 71:300–304.

    PubMed  CAS  Google Scholar 

  22. Carter CJ, Kelton JG, Hirsch J, et al.: The relationship between the hemorrhagic and antithrombotic properties of low molecular weight heparins in rabbits. Blood 1982, 59:1339–1345.

    Google Scholar 

  23. Bergqvist D, Burmark US, Frisell J, et al.: Prospective doubleblind comparison between Fragmin and conventional low-dose heparin: thromboprophylactic effect and bleeding complications. Haemostasis 1986, 16(suppl 2):11–18.

    PubMed  Google Scholar 

  24. Levine M, Gent M, Hirsch J, et al.: A comparison of lowmolecular weight heparin administered primarily at home with unfractionated heparin in the hospital for proximal deep-vein thrombosis. N Engl J Med 1996, 334:677–681.

    Article  PubMed  CAS  Google Scholar 

  25. Koopman MM, Prandoni P, Piovella F, et al.: Treatment of venous thrombosis with intravenous unfractionated heparin administered in the hospital as compared to subcutaneous low-molecular-weight heparin administered at home. N Engl J Med 1996, 334:682–687.

    Article  PubMed  CAS  Google Scholar 

  26. Cohen M, Demers C, Gurfinkel EP, et al.: A comparison of low-molecular-weight heparin with unfractionated heparin for unstable coronary artery disease. N Engl J Med 1997, 337:447–452.

    Article  PubMed  CAS  Google Scholar 

  27. Gurfinkel EP, Manos EJ, Mejail RI, 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.

    Article  PubMed  CAS  Google Scholar 

  28. 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.

    Google Scholar 

  29. Klein W, Buchwald A, Hillis SE, 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.

    PubMed  CAS  Google Scholar 

  30. Antman EM, McCabe CH, Gurfinkel EP, et al.: Enoxaparin prevents death and cardiac ischemic events in unstable angina/non-Q-wave myocardial infraction: Results of the Thrombolyis In Myocardial Infarction (TIMI) 11B Trial. Circulation 1999, 100:1593–1601. The TIMI 11B trial demonstrated that enoxaparin is more effective than unfractionated heparin in reducing the triple composite endpoint of death, myocardial infarction or urgent revascularization. This trial combined with the ESSENCE [26] trial collectively represent data in over 7000 patients demonstrating enoxaparin as superior to unfractionated heparin in the acute management of unstable angina and non-Q-wave myocardial infarction.

    PubMed  CAS  Google Scholar 

  31. The FRAX.I.S. 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: FRAX.I.S. (FRAxiparine in Ischaemic Syndrome). Eur Heart J 1999 20:1553–1562. FRAX.I.S. trials demonstrated nadroparin to be as effective and safe as UFH in the treatment of unstable angina and non-Q-wave myocardial infarction. Long-term treatment up to 14 days provided no additional benefit and was associated with higher bleeding complications.

    Article  Google Scholar 

  32. FRagmin and Fast Revascularization during InStability in Coronary artery disease (FRISC II) Investigators: Long-term low-molecular weight heparin in unstable coronary-artery disease: FRISC II prospective randomized multicenter study. Lancet 1999, 354:701–707. The FRISC II trial evaluated the long-term implications of dalteparin administration for 3 months following acute stabilization in patients with unstable angina and non-Q-wave myocardial infraction.

    Article  Google Scholar 

  33. Goodma S, Langer A, Demers C, et al.: One year follow-up of the ESSENCE trial (enoxaparin vs. heparin in unstabl angina/non-Q-wave myocardial infarction): sustained clinical benefit [abstract]. Can J Cardiol 1998, 14 122F.

    Google Scholar 

  34. Raschke, RA, Reilly RM, Guidry JR, et al.: The weight based heparin nomogram compared with a “standard care” nomogram: a randomized controlled trial. Ann Intern Med 1993, 119:874–881.

    PubMed  CAS  Google Scholar 

  35. Becker RC, Ball SP, Eisenberg P, et al.: A randomized, multicenter trial of weight-adjusted intravenous heparin dose titration and point-of-care coagulation monitoring in hospitalized patients with active thromboembolic disease. Am Heart J 1999, 137:59–71.

    Article  PubMed  CAS  Google Scholar 

  36. Antman EM, 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. This meta-analysis combined the results of the ESSENCE [26] and TIMI 11B [30*] trials and included over 7000 patients with unstable angina and non-Q-wave myocardial infarction. Results demonstrated.

    PubMed  CAS  Google Scholar 

  37. Mark DB, Cowper PA, Berkowitz SD, et al.: Economic assessment of low-molecular-weight heparin (enoxaparin) versus unfractionated heparin in acute coronary syndrome patients Results from the ESSENCE randomized trial. Circulation 1998, 97:1702–1707.

    PubMed  CAS  Google Scholar 

  38. Balen RM, Marra CA, Zed PJ, et al.: Cost-effectiveness analysis of enoxaparin versus unfractionated heparin for acute coronary syndromes: a Canadian hospital perspective. Pharmacoeconomics 1999, in press.

  39. Ernofsson M, Strekerud F, Toss H, et al.: Low-molecular weight heparin reduces the generation and activity of thrombin in unstable coronary artery disease. Thromb Haemost 1998, 79:491–494.

    PubMed  CAS  Google Scholar 

  40. Xiao Z, Theroux P: Platelet activation with unfractionated heparin at therapeutic concentration and comparisons with low-molecular weight heparin and with direct thrombin inhibitor. Circulation 1998, 97:251–256.

    PubMed  CAS  Google Scholar 

  41. Hansen J-B, Sandset PM: Differential effects of low molecular weight heparin and unfractionated heparin on circulating levels of antithrombin and tissue factor pathway inhibitor (TFPI): a possible mechanism for the difference in therapeutic efficacy. Thromb Res 1998, 91:177–181.

    Article  PubMed  CAS  Google Scholar 

  42. Montalescot G, Philippe F, Ankri A, et al.: Early increase of von Willebrand factor predicts adverse outcome in unstable coronary artery disease. Beneficial effects of enoxaparin. Circulation 1998, 98:294–299.

    PubMed  CAS  Google Scholar 

  43. The Platelet Receptor Inhibition in Ischemic Syndrome Management in Patients Limited by Unstable Signs and Symptoms (PRISM-PLUS) Study Investigators: Inhibition of the platelet glycoprotein IIb/IIIa receptor with tirofiban in unstable angina and non-Q-wave myocardial infraction. N Engl J Med 1998, 338:1488–1497.

    Article  Google Scholar 

  44. The PURSUIT Trial Investigators: Inhibition of platelet glycoprotein IIb/IIIa with eptifibatide in patients with acut coronary syndromes. N Engl J Med 1998, 339:436–443.

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. CSU Pharmaceutical Sciences, Vancouver Hospital and Health Sciences Center, 855 West 12th Avenue, V5Z 1M9, Vancouver, BC, Canada

    Peter J. Zed PharmD

Authors
  1. Peter J. Zed PharmD
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Zed, P.J. Low molecular weight heparins and coronary artery disease. Curr Cardiol Rep 2, 61–68 (2000). https://doi.org/10.1007/s11886-000-0027-0

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11886-000-0027-0

Keywords

Search

Navigation