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Thromb Haemost 2000; 83(01): 14-19
DOI: 10.1055/s-0037-1613749
Commentary
Schattauer GmbH

Prevention of Venous Thromboembolism in Internal Medicine with Unfractionated or Low-molecular-weight Heparins: A Meta-analysis of Randomised Clinical Trials

Patrick Mismetti
1   From the Clinical Pharmacology Unit, France
,
Silvy Laporte-Simitsidis
1   From the Clinical Pharmacology Unit, France
,
Bernard Tardy
2   From the Intensive Care Unit, Thrombosis Research Group, University Hospital of Saint-Etienne, France
,
Michel Cucherat
3   From the Clinical Pharmacology Unit, Cardiological Hospital of Lyon, France
,
Andréa Buchmüller
1   From the Clinical Pharmacology Unit, France
,
Daphné Juillard-Delsart
1   From the Clinical Pharmacology Unit, France
,
Hervé Decousus
1   From the Clinical Pharmacology Unit, France
› Author Affiliations
Further Information

Publication History

Received 16 March 1999

Accepted after revision 25 August 1999

Publication Date:
06 December 2017 (online)

Also available at
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Summary

Background

The prevention of venous thromboembolic disease is less studied in medical patients than in surgery.

Methods

We performed a meta-analysis of randomised trials studying prophylactic unfractionated heparin (UFH) or low-molecular-weight heparin (LMWH) in internal medicine, excluding acute myocardial infarction or ischaemic stroke. Deepvein thrombosis (DVT) systematically detected at the end of the treatment period, clinical pulmonary embolism (PE), death and major bleeding were recorded.

Results

Seven trials comparing a prophylactic heparin treatment to a control (15,095 patients) were selected. A significant decrease in DVT and in clinical PE were observed with heparins as compared to control (risk reductions = 56% and 58% respectively, p <0.001 in both cases), without significant difference in the incidence of major bleedings or deaths. Nine trials comparing LMWH to UFH (4,669 patients) were also included. No significant effect was observed on either DVT, clinical PE or mortality. However LMWH reduced by 52% the risk of major haemorrhage (p = 0.049).

Conclusions

This meta-analysis, based on the pooling of data available for several heparins, shows that heparins are beneficial in the prevention of venous thromboembolism in internal medicine.

Keywords

Heparin - internal medicine - venous thromboembolism - prophylaxis - meta-analysis
 

  • References

  • 1 Sandler DA, Martin JF. Autopsy proven pulmonary embolism in hospital patients: are we detecting enough deep vein thrombosis?. J Royal Soc Med 1989; 82: 198-200.
    CrossrefPubMedSearch in Google Scholar
  • 2 Goldhaber SZ, Hennekens CH, Evans DA, Newton EC, Godleski JJ. Factors associated with an antemorten diagnosis of major pulmonary embolism. Am J Med 1982; 73: 822-6.
    CrossrefPubMedSearch in Google Scholar
  • 3 Anderson FA, Wheeler HB. Physician practices in the management of venous thromboembolism: a community-wide survey. J Vasc Surg 1992; 16: 707-14.
    CrossrefPubMedSearch in Google Scholar
  • 4 Thromboembolic Risk Factors (THRIFT) Consensus Group. Risk of and prophylaxis for venous thromboembolism in hospital patients. Br Med J 1992; 305: 567-74.
    CrossrefPubMedSearch in Google Scholar
  • 5 Anderson FA, Wheeler HB, Goldberg RJ. et al A population-based perspective of the hospital incidence and case-facility rates of deep vein thrombosis and pulmonary embolism. The Worcester DVT study. Arch Intern Med 1991; 151: 933-8.
    CrossrefPubMedSearch in Google Scholar
  • 6 Collins R, Scrimgeour A, Yusuf S, Peto R. Reduction in fatal pulmonary embolism and venous thrombosis by perioperative administration of subcutaneous heparin. N Engl J Med 1988; 318: 1162-73.
    CrossrefPubMedSearch in Google Scholar
  • 7 Leizorovicz A, Haugh MC, Chapuis FR, Samama MM, Boissel JP. Low molecular weight heparin in prevention of perioperative thrombosis. Br Med J 1992; 305: 913-20.
    CrossrefPubMedSearch in Google Scholar
  • 8 Mismetti P, Laporte-Simitsidis S, Tardy B, Queneau P, Decousus H. Prophylaxis of post operative venous thrombosis and pulmonary embolism by oral anticoagulants: a meta-analysis. Clinical Trials Meta-Analysis 1993; 28: 227-40.
    PubMedSearch in Google Scholar
  • 9 Nurmohamed MT, Rosendaal FR, Buller HR. et al Low-molecular-weight heparin versus standard heparin in general and orthopaedic surgery: a metaanalysis. Lancet 1992; 340: 152-6.
    CrossrefPubMedSearch in Google Scholar
  • 10 Counsell C, Sandercock P. The efficacy and safety of anticoagulant therapy in patients with acute presumed ischaemic stroke: a systematic review of the randomized trials comparing anticoagulants with control. In: Warlow C, Van Gijn J, Sandercock P. The Cochrane Database Library. Cochrane Collaboration; issue 1. Oxford: update Software 1997..
  • 11 Collins R, MacMahon S, Flather M. et al Clinical effects of anticoagulant therapy in suspected acute myocardial infarction: systematic overview of randomised trials. Br Med J 1996; 313: 652-9.
    CrossrefPubMedSearch in Google Scholar
  • 12 Lau J, Antman EM, Jimenez-Silva J, Kupelnick B, Mosteller F, Chalmers TC. Cumulative meta-analysis of therapeutic trials for myocardial infarction. N Engl J Med 1992; 327: 248-54.
    CrossrefPubMedSearch in Google Scholar
  • 13 Cucherat M, Boissel JP, Leizorovicz A, Haugh MC. EasyMA: a program for the meta-analysis of clinical trials. Comp Methods Prog Biomed 1997; 53: 187-90.
    CrossrefPubMedSearch in Google Scholar
  • 14 Belch JJ, Lowe GDO, Ward AG, Forbes CD, Prentice CRM. Prevention of deep vein thrombosis in medical patients by low-dose heparin. Scott Med J 1981; 26: 115-7.
    CrossrefPubMedSearch in Google Scholar
  • 15 Cade JF, Andrews JT, Stubbs AE. Comparison of sodium and calcium heparin in prevention of venous thromboembolism. Aust N Z J Med 1982; 12: 501-4.
    CrossrefPubMedSearch in Google Scholar
  • 16 Dahan R, Houlbert D, Caulin C. et al Prevention of deep vein thrombosis in elderly medical in-patients by a low molecular weight heparin: a randomized double blind trial. Haemostasis 1986; 16: 159-64.
    PubMedSearch in Google Scholar
  • 17 Ibarra-Perez C, Lau-Cortes E, Colmenero-Zubiate S. et al Prevalence and prevention of deep venous thrombosis of the lower extremities in high risk pulmonary patients. Angiology 1988; 39: 503-13.
    PubMedSearch in Google Scholar
  • 18 Bergmann JF, Caulin C. Heparin prophylaxis in bedridden patients. Lancet 1996; 348: 205-6.
    PubMedSearch in Google Scholar
  • 19 Gärdlung B. for the Heparin Prophylaxis Group. Randomized, controlled trial of low-dose heparin for prevention of fatal pulmonary embolism in patients with infectious diseases. Lancet 1996; 347: 1357-61.
    CrossrefPubMedSearch in Google Scholar
  • 20 Fraisse E, Holzapfel L, Coulaud JM. et al Efficacy and safety of calcium Nadroparin (Fraxiparine®) in the prevention of deep-vein thrombosis during acute phase of chronic obstructive pulmonary disease. Submitted for publication 1998. Data provided by Sanofi Winthrop..
    PubMed
  • 21 Halkin H, Goldberg J, Modan M, Modan B. Reduction of mortality in general medical in-patients by low-dose heparin prophylaxis. Ann Intern Med 1982; 96: 561-5.
    CrossrefPubMedSearch in Google Scholar
  • 22 Poniewierski M, Barthels M, Kuhn M, Poliwoda H. Effectiveness of low molecular weight heparin (Fragmin®) in the prevention of thromboembolism in internal medicine patients. A randomized double blind study. Med Klin 1988; 83: 241-5.
    PubMedSearch in Google Scholar
  • 23 Aquino JP, Gambier A, Ducros J. Prevention of thromboembolic accidents in elderly subjects with Fraxiparine. In: Fraxiparine, 2nd international symposium. Recent pharmacological and clinical data. Bounameaux H, Samama MM, Ten Cate JW. Stuttgart, New York: Schattauer; 1990: 51-4.
    Search in Google Scholar
  • 24 Harenberg J, Kallenbach B, Martin U. et al Randomised controlled study of heparin and low molecular weight heparin for prevention of deep-vein thrombosis in medical patients. Thromb Res 1990; 59: 639-50.
    CrossrefPubMedSearch in Google Scholar
  • 25 Forette B, Wolmark Y. Calcium nadroparin in the prevention of thromboembolic disease in elderly subjects. Study of tolerance. Presse Med 1995; 24: 567-71.
    PubMedSearch in Google Scholar
  • 26 Harenberg J, Roebruck P, Heene DL. Subcutaneous low-molecular-weight heparin versus standard heparin and the prevention of thromboembolism in medical inpatients. The Heparin Study in Internal Medicine (HESIM) Group. Haemostasis 1996; 26: 127-39.
    PubMedSearch in Google Scholar
  • 27 Manciet G, Vergnes C, Vaissié JJ, Boisseau MR. Étude de l’efficacité et de la tolérance de Fraxiparine® administrée au long cours chez le sujet âgé: étude randomisée en double insu (APTE). Bounameaux H, Samama MM, Ten Cate JW. Stuttgart, New York: Schattauer; 1990: 55-9.
    Search in Google Scholar
  • 28 Lechler E, Schramm W, Flosbach CW. The venous thrombotic risk in nonsurgical patients: epidemiologal data and efficacy/safety profile of a low molecular weight heparin (enoxaparin). The PRIME Study Group. Haemostasis 1996; 26: 49-56.
    PubMedSearch in Google Scholar
  • 29 Bergmann JF, Neuhart E. from the Enoxaparin in Medicine Study Group (EMSG). A multicenter randomized double-blind study of enoxaparin compared with unfractionated heparin in the prevention of venous thromboembolic disease in elderly in-patients bedridden for an acute medical illness. Thromb Haemost 1996; 76: 529-34.
    PubMedSearch in Google Scholar
  • 30 Kleber FX, Witt C, Flosbach CW, Koppenhagen K, Vogel G. and the PRINCE study group. Study to compare the efficacy and safety of the LMWH Enoxaparin and standard heparin in the prevention of thromboembolic events in medical patients with cardiopulmonary diseases. Ann Hematol 1998; 76 (Suppl. 01) P261.
    PubMedSearch in Google Scholar
  • 31 Cogo A, Bernardi E, Prandoni P. et al Acquired risk factors for deep vein thrombosis in symptomatic outpatients. Arch Intern Med 1994; 154: 164-8.
    CrossrefPubMedSearch in Google Scholar