BMJ 1994;309:299-304 (30 July)

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Comparison of efficacy and safety of low molecular weight heparins and unfractionated heparin in initial treatment of deep venous thrombosis: a meta-analysis

A Leizorovicz, G Simonneau, H Decousus, J P Boissel 

Service de Pharmacologie Clinique, BP 3041, 69394 Lyons Cedex 03, France Service de Pneumologie, Hopital A, Beclere, 92140 Clamart, France Hopital Bellevue, 42023 St Etienne Cedex, France Correspondence to: Dr Leizorovicz.

Abstract

Objective : To compare the efficacy and safety of low molecular weight heparins and unfractionated heparin in the initial treatment of deep venous thrombosis for the reduction of recurrent thromboembolic events, death, extension of thrombus, and haemorrhages.
Design : Meta-analysis of results from 16 randomised controlled clinical studies.
Subjects : 2045 patients with established deep20venous thrombosis.
Intervention : Treatment with low molecular weight heparins or unfractionated heparin.
Main outcome measures : Incidences of thromboembolic events (deep venous thrombosis or pulmonary embolism, or both); major haemorrhages; total mortality; and extension of thrombus.
Results : A significant reduction in the incidence20of thrombus extension (common odds ratio 0.51, 95% confidence interval 0.32 to 0.83; P=0.006) in favour of low molecular weight heparin was observed. Non-significant trends also in favour of the low molecular weight heparins were observed for the recurrence of thromboembolic events (0.66, 0.41 to 1.07; P=0.09), major haemorrhages (0.65, 0.36 to 1.16; P=0.15), and total mortality (0.72, 0.46 to 1.4; P=0.16).
Conclusions : Low molecular weight heparins seem to have a higher benefit to risk ratio than unfractionated heparin in the treatment of venous thrombosis. These results, however, remain to be confirmed by using clinical outcomes in suitably powered clinical trials.

Clinical implications

  • Clinical implications

  • Unfractionated heparin as a first line treatment followed by an oral anticoagulant is the accepted therapeutic approach for deep venous thrombosis

  • Despite treatment, 5-10% of patients suffer from recurrent thromboembolic events in the months after the initial deep venous thrombosis

  • More than 2000 patients have been enrolled in 16 controlled clinical trials comparing the efficacy and safety of low molecular weight heparins and unfractionated heparin; none of these trials allows definitive conclusions to be drawn

  • The results from this meta-analysis show a global significant trend in favour of low molecular weight heparins for a venographic outcome (thrombus extension); although there were favourable trends for clinical outcomes (recurrent thromboembolic events, mortality) and apparently better safety (major haemorrhage), these did not reach significance

  • Although some clinicians may even now prefer to use low molecular weight heparins because they are easier to administer and do not require adjustment of the dose by laboratory analysis, their clinical superiority needs to be confirmed in larger scale clinical trials


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Relevant Article

Possible benefits of low molecular weight heparins
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BMJ 1994 309: 1019. [Extract] [Full Text]

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