Low molecular weight heparin administered once versus twice daily in patients with venous thromboembolism: a meta-analysis

Thromb Haemost. 2001 Oct;86(4):980-4.


Background: Low molecular weight heparin is as effective and safe as unfractionated heparin for treatment of acute venous thromboembolism. It is uncertain whether low molecular weight heparin should be administered once-daily or twice-daily in this setting.

Method: A meta-analysis of randomized studies which directly compared once- and twice-daily administration of low molecular weight heparin for the treatment of acute venous thromboembolism was performed. A literature search was performed using Advanced Pub Med and the Cochrane library database, and abstracts from recent meetings were reviewed. Two investigators extracted data independently.

Results: Five studies, involving 1522 patients, were eligible. There were no statistically significant differences in the frequencies of symptomatic (odds ratio, 0.85 in favor of once-daily therapy at three months, p = 0.6), and asymptomatic, recurrent venous thromboembolism, total and major bleeds (odds ratio, 1.16 in favor of twice-daily therapy at 10 days, p = 0.8); and death, at 10 days, as well as at three months of follow-up.

Conclusion: Once-daily low molecular weight heparin appears to be as effective and safe as twice-daily administration for the acute treatment of venous thromboembolism. However, there is inadequate data from studies that directly compared once-daily and twice-daily administration to be able to exclude the possibility of a higher frequency of fatal bleeding with once-daily therapy.

Publication types

  • Comparative Study
  • Meta-Analysis
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Anticoagulants / administration & dosage*
  • Anticoagulants / adverse effects
  • Anticoagulants / therapeutic use
  • Dalteparin / therapeutic use
  • Drug Administration Schedule
  • Enoxaparin / therapeutic use
  • Hemorrhage / chemically induced
  • Hemorrhage / mortality
  • Heparin, Low-Molecular-Weight / administration & dosage*
  • Heparin, Low-Molecular-Weight / adverse effects
  • Heparin, Low-Molecular-Weight / therapeutic use
  • Humans
  • Nadroparin / therapeutic use
  • Odds Ratio
  • Pulmonary Embolism / drug therapy*
  • Pulmonary Embolism / mortality
  • Randomized Controlled Trials as Topic
  • Recurrence
  • Survival Analysis
  • Thromboembolism / drug therapy*
  • Thromboembolism / mortality
  • Treatment Outcome
  • Venous Thrombosis / drug therapy*
  • Venous Thrombosis / mortality


  • Anticoagulants
  • Enoxaparin
  • Heparin, Low-Molecular-Weight
  • Nadroparin
  • Dalteparin