Download PDF
Thromb Haemost 2000; 83(05): 652-656
DOI: 10.1055/s-0037-1613886
Review Article
Schattauer GmbH

Fixed-dose, Body Weight-independent Subcutaneous LMW Heparin versus Adjusted Dose Unfractionated Intravenous Heparin in the Initial Treatment of Proximal Venous Thrombosis

J. Harenberg
1   From the Dept. of Medicine, University Hospital, Mannheim, Germany
,
J. A. Schmidt
2   Dept. of Angiology, Otto-von-Guericke-University, Magdeburg, Germany
,
K. Koppenhagen
3   Dept. of Radiology, Benjamin Franklin University, Berlin, Germany
,
A. Tolle
4   Novartis Pharma GmbH, Nuremberg, Germany
,
M. V. Huisman
5   Dept. of General Internal Medicine, University Hospital, Leiden, Netherlands
,
H. R. Büller
6   Dept. of Vascular Medicine, Academic Medical Center, Amsterdam, Netherlands
,
the EASTERN Investigators › Author Affiliations
Further Information

Publication History

Received 22 July 1999

Accepted after resubmission 17 January 2000

Publication Date:
08 December 2017 (online)

Also available at
    Permissions and Reprints

Summary

Background

Body weight-adjusted subcutaneous low-molecular-weight heparin (LMWH) has been proven to be at least as effective and safe as dose-adjusted intravenous unfractionated heparin (UFH) for the treatment of patients with venous thromboembolism. However, body weight-adjusted dosage of low-molecular-weight heparin may be cumbersome and could lead possibly to incorrect dosing. Therefore a fixed LMWH dose, independent of body-weight, might rationalize initial treatment for venous thromboembolism.

Methods

Patients with proven proximal deep-vein thrombosis were randomly assigned to fixed dose subcutaneous LMWH Certoparin (8,000 anti-factor Xa U b.i.d.; 265 patients) or to adjusted dose i.v. UFH (273 patients) for 12 days. Vitamin K antagonists were started between day 3 and 7 and continued for up to 6 months. The primary outcome measure was a 30 percent or greater improvement in the Marder Score, as revealed by repeated venography on day 12 (end of the initial treatment). The secondary composite outcome measure included death, recurrent venous thromboembolism and major bleeding and was assessed at day 12 and after 6 months by a blinded adjunction committee.

Results

The Marder score improved by 30% or more in 30.3% and 25.0% of patients assigned to LMWH (198 paired venograms) and UFH (192 paired venograms), respectively (2p = 0.26). At the end of the initial treatment, the composite outcome was observed in 4 of the 265 patients (1.5%) randomized to LMWH, as compared with 14 of the 273 patients (5.1%) randomized to UFH (2p = 0.03). At 6 months these figures were 6.8% and 12.8%, respectively (risk reduction 0.53, confidence interval 0.31-0.90, 2p = 0.02).

Conclusion

Fixed dose subcutaneous LMWH certoparin is at least as efficacious as UFH in resolving proximal vein thrombosis. With respect to the composite outcome of death, recurrent venous thromboembolism and major bleeding LMWH treatment performed significantly better both during initial therapy and at a six-month follow-up.

Keywords

Venous thromboembolism - treatment - composite outcome - LMW heparin - fixed-dose body weight-independent heparin regimen

* The investigators and the centers participating are listed in the appendix, pp. 655–6.


 

  • References

  • 1 Hyers TM, Agnelli G, Hull R, Weg JG, Morris TA, Sammama M, Tapson V. Antithrombotic therapy for venous thromboembolic disease. Chest 1998; 114: 561-78.
    CrossrefPubMedSearch in Google Scholar
  • 2 Levine M, Gent M, Hirsh J, Leclerc J, Anderson D, Weitz J, Ginsberg JS, Turpie AG, Demers C, Kovacs M. A comparison of low-molecular-weight heparin administered primarily at home with unfractionated heparin administered in the hospital for proximal deep-vein-thrombosis. N Engl J Med 1996; 334: 677-81.
    CrossrefPubMedSearch in Google Scholar
  • 3 Koopman MMW, Prandoni P, Piovella F, Ockford PA, Brandjes DP, Van der Meer J, Gallus AS, Simonneau G, Chesterman CH, Prins MH. Treatment of patients with proximal-vein thrombosis with intravenous unfrationated heparin in hospital compared with subcutaneous low-molecular-weight heparin out of hospital or with early discharge. N Engl J Med 1996; 334: 682-7.
    CrossrefPubMedSearch in Google Scholar
  • 4 Simonneau G, Sors H, Charbonnier B, Page Y, Laaban J-P, Azarian R, Laurent M, Hirsch J-L, Ferrari E, Bosson J-L, Mottier D, Beau B. for the THÉSÉE Study Group. A comparison of low-molecular-weight heparin with unfractionated heparin for acute pulmonary embolism. N Engl J Med 1997; 337: 663-9.
    CrossrefPubMedSearch in Google Scholar
  • 5 The Columbus Investigators. Low-molecular-weight heparin in the treatment of patients with venous thromboembolism. N Engl J Med 1997; 337: 657-62.
    CrossrefPubMedSearch in Google Scholar
  • 6 Weitz JI. Low Molecular Weight Heparins. N Engl J Med 1997; 337: 688-98.
    CrossrefPubMedSearch in Google Scholar
  • 7 Ginsberg JS. Management of venous thromboembolism. N Engl J Med 1996; 335: 1816-28.
    CrossrefPubMedSearch in Google Scholar
  • 8 Kirchmaier CM, Lindhoff-Last E, Rübsam D, Scharrer I, Vigh ZS, Mosch G, Wolf H, Breddin HK. Regression of deep vein thrombosis by iv.administration of a low molecular weight heparin – results of a pilot study. Thromb Res 1994; 73: 337-48.
    CrossrefPubMedSearch in Google Scholar
  • 9 Harenberg J, Huck K, Bratsch H, Stehle G, Dempfle CE, Mall K, Blauth M, Usadel KH, Heene DL. Therapeutic application of subcutaneous low-molecular-weight heparin in acute venous thrombosis. Haemostasis 1990; 20 (Suppl. 01) 205-19.
    PubMedSearch in Google Scholar
  • 10 Kirchmaier CM, Wolf H, Schäfer H, Ehlers B, Breddin HK. for the certoparin-Study group. Efficacy of a low molecular weight heparin administered intravenously or subcutaneously in comparison with intravenous unfractionated heparin in the treatment of deep venous thrombosis. Int Angiol 1998; 17: 135-45.
    PubMedSearch in Google Scholar
  • 11 Rabinov K, Paulin S. Roentgen diagnosis of venous thrombosis in the leg. Arch Surg 1972; 104: 134-44.
    CrossrefPubMedSearch in Google Scholar
  • 12 Gallus A, Jackaman J, Tillett J, Mills W, Wycherley A. Safety and efficacy of warfarin started early after submassive venous thrombosis or pulmonary embolism. Lancet 1986; II: 1293-6.
    PubMedSearch in Google Scholar
  • 13 Hull RD, Raskob GE, Rosenbloom D, Panju AA, Brill PEdwards, Ginsberg JS, Hirsh J, Martin GJ, Green D. Heparin for 5 days as compared with 10 days in the initial treatment of proximal venous thrombosis. N Engl J Med 1990; 322: 1260-4.
    CrossrefPubMedSearch in Google Scholar
  • 14 The PIOPED Investigators. Value of the ventilation/perfusion scan in acute pulmonary embolism: results of the Prospective Investigation of Pulmonary Embolism Diagnosis (PIOPED). JAMA 1990; 263: 2753-9.
    CrossrefPubMedSearch in Google Scholar
  • 15 Marder VJ, Soulen RL, Atichartakan V, Budzynski AZ, Parulekar S, Kim IR. Quantitative venography assessment of deep vein thrombosis in the evaluation of streptokinase and heparin therapy. J Lab Clin Med 1977; 89: 1018-29.
    PubMedSearch in Google Scholar
  • 16 Prandoni P, Lensing AW, Buller HR, Carta M, Cogo A, Vigo M, Casara D, Ruol A, ten Cate JW. Comparison of subcutaneous low-molecular-weight heparin with intravenous standard heparin in proximal deep-vein thrombosis. Lancet 1992; 339: 441-5.
    CrossrefPubMedSearch in Google Scholar
  • 17 Brandjes DP, Heijboer H, Buller HR, de Rijk M, Jagt H, ten Cate JW. Acenocoumarol and heparin compared with acenocoumarol alone in the initial treatment of proximal-vein thrombosis. N Engl J Med 1992; 327: 1485-9.
    CrossrefPubMedSearch in Google Scholar
  • 18 Lensing AWA, Prins MH, Davidson BL, Hirsh J. Treatment of deep venous thrombosis with low-molecular-weight heparins. A meta-analysis. Arch Intern Med 1995; 155: 601-7.
    PubMedSearch in Google Scholar
  • 19 Siragusa S, Cosmi B, Piovella F, Hirsh J, Ginsberg JS. Low-molecular-weight heparins and unfractionated heparin in the treatment of patients with acute venous thromboembolism: results of a meta-analysis. Am J Med 1996; 100: 269-77.
    CrossrefPubMedSearch in Google Scholar
  • 20 Bratt G, Törnbohm E, Graqvist St, Aberg W, Lockner D. A comparison between low molecular weight heparin (KABI 2165) and standard heparin in the intravenous treatment of deep venous thrombosis. Thromb Haemost 1985; 54: 813-7.
    Thieme ConnectPubMedSearch in Google Scholar