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


OBJECTIVE
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.


METHODS
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.


METHODS
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.


METHODS
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.


RESULTS
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.
Quinlan
Daniel J
DJ
King's College Hospital, London, United Kingdom.
McQuillan
Andrew
A
Eikelboom
John W
JW
D006470:Hemorrhage / Q000139:chemically induced; D006493:Heparin / Q000009:adverse effects / Q000627:therapeutic use*; D006495:Heparin, Low-Molecular-Weight / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D007275:Injections, Intravenous; D007279:Injections, Subcutaneous; D009026:Mortality; D011446:Prospective Studies; D011655:Pulmonary Embolism / Q000188:drug therapy*; D016032:Randomized Controlled Trials as Topic; D012008:Recurrence; D012680:Sensitivity and Specificity; D020246:Venous Thrombosis / Q000150:complications / Q000188:drug therapy
D006495:Heparin, Low-Molecular-Weight; D006493:Heparin