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Thromb Haemost 1998; 79(05): 897-901
DOI: 10.1055/s-0037-1615089
Review Article
Schattauer GmbH

Comparison of a once Daily with a twice Daily Subcutaneous Low Molecular Weight Heparin Regimen in the Treatment of Deep Vein Thrombosis

Bernard A. Charbonnier
1   From the University Hospital Trousseau, Tours, France
,
Jean-Noël Fiessinger
2   From the Broussais Hospital, Paris, France
,
J. D. Banga
3   From the Academic Hospital, Utrecht, The Netherlands
,
Ernst Wenzel
4   From the Universitätskliniken, Homburg/Saar, Germany
,
Pascal d’Azemar
5   From the Sanofi Recherche, Gentilly, France
,
Luc Sagnard
5   From the Sanofi Recherche, Gentilly, France
,
FRAXODI group › Author AffiliationsThis study was supported by a grant from Sanofi-Recherche.
Further Information

Publication History

Received 22 September 1997

Accepted after revision 16 December 1997

Publication Date:
07 December 2017 (online)

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Summary

Background: Clinical trials have been performed to compare with standard heparin a once or a twice daily regimen of low-molecular-weight heparin but no direct comparison has been done between these two low-molecular-weight heparin regimens in terms of efficacy and safety with a long-term clinical evaluation.

Methods: Patients with proximal deep vein thrombosis, confirmed by venography were randomly assigned to either nadroparin (10,250 AXa IU/ml) twice daily or nadroparin (20,500 AXa IU/ml) once daily for at least 5 days. Regimens were adjusted to bodyweight. Oral anticoagulants were started on day 1 or 2 and continued for 3 months. Patients were followed up for 3 months. The composite outcome of venous thromboembolism and death possibly related to pulmonary embolism was the primary measure of efficacy. Major bleeding was the principal measure of safety. The study was designed to show equivalence between the two regimens.

Results: Recurrent thromboembolic events or death possibly related to pulmonary embolism were reported in 13 patients in the once daily group (4.1%) and in 24 patients of the twice daily group (7.2%): (absolute difference 3.1% in favor of the once daily regimen; 95% confidence interval -6.6%, +0.5%). Major bleeding episodes during nadroparin treatment occurred in 4 (1.3%) and 4 patients (1.2%) in the once and twice daily groups, respectively.

Conclusions: A nadroparin regimen of one injection per day is at least as effective and safe as the same total daily dose divided over two injections for the treatment of acute deep vein thrombosis.

 

  • References

  • 1 Leizorovicz A, Simonneau G, Decousus H, Boissel JP. Comparison of efficacy and safety of low-molecular-weight heparins and unfractionated heparin in initial treatment of deep venous thrombosis: a meta-analysis. BMJ 1994; 309: 299-304.
    CrossrefPubMedGoogle Scholar
  • 2 Lensing AWA, Prins MH, Davidson BL, Hirsh J. Treatment of deep venous thrombosis with low-molecular-weight heparins. A metaanalysis. Arch Intern Med 1995; 155: 601-7.
    CrossrefPubMedGoogle Scholar
  • 3 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. The American Journal of Medicine 1996; 100: 269-77.
    CrossrefPubMedGoogle Scholar
  • 4 Levine M, Gent M, Hirsh J, Leclerc J, Anderson D, Weitz J, Ginsberg J, Turpie AG, Demers C, Kovacs M, Geerts W, Kassis J, Desjardins L, Cusson J, Cruickshank M, Powers P, Brien W, Haley S, Willan A. 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: 671-81.
    CrossrefPubMedGoogle Scholar
  • 5 Koopman MMW, Prandoni P, Piovella F, Ockelford PA, Brandjes DPM, van der Meer J, Gallus AS, Simmoneau G, Chesterman CH, Prins MH, Bossuyt PMM, de Haes H, van den Belt AGM, Sagnard L, d’Azémar P, Bueller HR. Treatment of venous thrombosis with intravenous unfractionated heparin administered in the hospital as compared with subcutaneous low-molecular-weight heparin administered at home. N Engl J Med 1996; 334: 682-7.
    CrossrefPubMedGoogle Scholar
  • 6 Ninet J, Bachet P, Prandoni P, Ruol A, Vigo M, Barret A, Mericq O, Boneu B, Janvier G, Duroux P, Girard P, Laprevote-Heully MC, Sourou P, Robert D, Chagny M, Nenci G, Agnelli G, D’Addata M, Palumbo H, Bensaid J. A randomised trial of subcutaneous low-molecular-weight heparin (CY 216) compared with intravenous unfractionated heparin in the treatment of deep vein thrombosis – A collaborative European multicentre study. Thromb Haemost 1991; 65 (03) 251-6.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 7 Théry C, Simonneau G, Meyer G, Helenon O, Bridey F, Armagnac C, d’Azémar P, Coquart JP. Randomized trial of subcutaneous low-molecular-weight heparin CY 216 (Fraxiparine) compared with intravenous unfractionated heparin in the curative treatment of submassive pulmonary embolism. A dose ranging study. Circulation 1992; 85: 1380-9.
    CrossrefPubMedGoogle Scholar
  • 8 Lopaciuk S, Meissner A, Filipecki S, Zawilska K, Sowier J, Ciesielski L, Bielawiec M, Glowinski S, Czestochowska E. Subcutaneous low molecular weight heparin versus subcutaneous unfractionated heparin in the treatment of deep vein thrombosis: a Polish multicenter trial. Thromb Haemost 1992; 68 (01) 14-8.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 9 Prandoni P, Lensing AWA, Büller 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. The Lancet 1992; 339: 441-5.
    CrossrefPubMedGoogle Scholar
  • 10 Mismetti P, Laporte-Simitsidis S, Boneu B, d’Azémar P, Gaud C, Duret JP, Decousus H. Pharmacodynamic study of a repeated once daily curative dosage of nadroparin (FRAXIPARINE® ) in twelve elderly healthy volunteers. Haemostasis. 1996 vol 2b (Suppl. 3), abstract n° 93.
    PubMedGoogle Scholar
  • 11 Blackweldeer WC. “Proving the null hypothesis” in clinical, controlled clinical trials. 1982; 3: 345-53.
    PubMedGoogle Scholar
  • 12 Hull RD, Raskob GE, Pineo GF, Green D, Trowbridge AA, Elliott CG, Lerner RG, Hall J, Sparling T, Bretteli HR, Norton J, Carter CJ, George R, Merli G, Ward J, Mayo W, Rosenbloom D, Brant R. Subcutaneous low-molecular-weight heparin compared with continuous intravenous heparin in the treatment of proximal-vein thrombosis. N Engl J Med 1992; 326: 975-82.
    CrossrefPubMedGoogle Scholar
  • 13 Brandjes DPM, Heijboer H, Büller 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: 21.
    PubMedGoogle Scholar
  • 14 Lindmarker P, Holmström M, Granqvist S, Johnson H, Lockner D. Comparison of once-daily subcutaneous Fragmin® with continuous intravenous unfractionated heparin in the treatment of deep vein thrombosis. Thromb Haemost 1994; 72 (02) 186-90.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 15 Fiessinger JN, Lopez-Fernandez M, Gatterer E, Granqvist S, Kher A, Olsson CG, Söderberg K. Once-daily subcutaneous Dalteparin, a low molecular weight heparin, for the initial treatment of acute deep vein thrombosis. Thromb Haemost 1996; 76 (02) 195-9.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 16 Luomanmäki K, Grankvist S, Hallert C, Jauro I, Ketola K, Kim HC, Kiviniemi H, Koskivirta H, Sörskog L, Vilkko P. A multicentre comparison of once-daily subcutaneous dalteparin (low molecular weight heparin) and continuous intravenous heparin in the treatment of deep vein thrombosis. Journal of Internal Medicine 1996; 240: 85-92.
    CrossrefPubMedGoogle Scholar