Low-molecular-weight heparin compared with intravenous unfractionated heparin for treatment of pulmonary embolism: a meta-analysis of randomized, controlled trials

Ann Intern Med. 2004 Feb 3;140(3):175-83. doi: 10.7326/0003-4819-140-3-200402030-00008.


Background: Low-molecular-weight heparin has greatly simplified the management of deep venous thrombosis. However, for patients who present with pulmonary embolism, the role of low-molecular-weight heparin is uncertain and unfractionated heparin remains widely used.

Purpose: To compare the efficacy and safety of fixed-dose subcutaneous low-molecular-weight heparin with that of dose-adjusted intravenous unfractionated heparin to treat acute pulmonary embolism.

Data sources: The MEDLINE, EMBASE, and Cochrane Library databases were searched up to 1 August 2003. Additional data sources were manual searches of abstract proceedings and personal contact with investigators and pharmaceutical companies.

Study selection: Randomized trials comparing fixed-dose subcutaneous low-molecular-weight heparin with dose-adjusted intravenous unfractionated heparin for the treatment of nonmassive symptomatic pulmonary embolism or asymptomatic pulmonary embolism in the context of symptomatic deep venous thrombosis.

Data extraction: Two reviewers independently selected studies and extracted data on study design; quality; and clinical outcomes, including symptomatic venous thromboembolism, death, and major and minor bleeding. Odds ratios for individual outcomes were calculated for each trial and were pooled by using the Mantel-Haenszel method.

Data synthesis: Fourteen trials involving 2110 patients with pulmonary embolism met the inclusion criteria. Separate outcome data for patients with pulmonary embolism were not available from 2 trials (159 patients), leaving 12 trials for meta-analysis. Compared with unfractionated heparin, low-molecular-weight heparin was associated with a non-statistically significant decrease in recurrent symptomatic venous thromboembolism at the end of treatment (1.4% vs. 2.4%; odds ratio, 0.63 [95% CI, 0.33 to 1.18]) and at 3 months (3.0% vs. 4.4%; odds ratio, 0.68 [CI, 0.42 to 1.09]). Similar estimates were obtained for patients who presented with symptomatic pulmonary embolism (1.7% vs. 2.3%; odds ratio, 0.72 [CI, 0.35 to 1.48]) or asymptomatic pulmonary embolism (1.2% vs. 3.2%; odds ratio, 0.53 [CI, 0.15 to 1.88]). For major bleeding complications, the odds ratio favoring low-molecular-weight heparin (1.3% vs. 2.1%; odds ratio, 0.67 [CI, 0.36 to 1.27]) was also not statistically significant.

Conclusions: Fixed-dose low-molecular-weight heparin treatment appears to be as effective and safe as dose-adjusted intravenous unfractionated heparin for the initial treatment of nonmassive pulmonary embolism.

Publication types

  • Meta-Analysis

MeSH terms

  • Hemorrhage / chemically induced
  • Heparin / adverse effects
  • Heparin / therapeutic use*
  • Heparin, Low-Molecular-Weight / adverse effects
  • Heparin, Low-Molecular-Weight / therapeutic use*
  • Humans
  • Injections, Intravenous
  • Injections, Subcutaneous
  • Mortality
  • Prospective Studies
  • Pulmonary Embolism / drug therapy*
  • Randomized Controlled Trials as Topic
  • Recurrence
  • Sensitivity and Specificity
  • Venous Thrombosis / complications
  • Venous Thrombosis / drug therapy


  • Heparin, Low-Molecular-Weight
  • Heparin