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Low-Molecular-Weight Heparins Compared with Unfractionated Heparin for Treatment of Acute Deep Venous Thrombosis
A Meta-Analysis of Randomized, Controlled Trials
- Michael K. Gould, MD, MSc;
- Anne D. Dembitzer, MD;
- Ramona L. Doyle, MD;
- Trevor J. Hastie, PhD; and
- Alan M. Garber, MD, PhD
- From Veterans Affairs Palo Alto Health Care System, Palo Alto, California; and Stanford University, Stanford, California.
Abstract
Background: Low-molecular-weight heparins may simplify the management of deep venous thrombosis. A critical clinical issue is whether this more convenient therapy is as safe and effective as treatment with unfractionated heparin.
Purpose: To compare the safety and efficacy of low-molecular-weight heparins with those of unfractionated heparin for treatment of acute deep venous thrombosis.
Data Sources: Reviewers identified studies by searching MEDLINE, reviewing references from retrieved articles, scanning abstracts from conference proceedings, and contacting investigators and pharmaceutical companies.
Study Selection: Randomized, controlled trials that compared a low-molecular-weight heparin preparation with unfractionated heparin for treatment of acute deep venous thrombosis.
Data Extraction: Two reviewers extracted data independently. Reviewers evaluated study quality using a validated four-item instrument.
Data Synthesis: Eleven of 37 studies met inclusion criteria for three major outcomes. Most studies used proper randomization procedures, but only one was double-blinded. Compared with unfractionated heparin, low-molecular-weight heparins reduced mortality rates over 3 to 6 months of patient follow-up (odds ratio, 0.71 [95% CI, 0.53 to 0.94]; P = 0.02). For major bleeding complications, the odds ratio favored low-molecular-weight heparins (0.57 [CI, 0.33 to 0.99]; P = 0.047), but the absolute risk reduction was small and not statistically significant (0.61% [CI, −0.04% to 1.26%]; P = 0.07). For preventing thromboembolic recurrences, low-molecular-weight heparins seemed as effective as unfractionated heparin (odds ratio, 0.85 [CI, 0.63 to 1.14]; P > 0.2).
Conclusions: Low-molecular-weight heparin treatment reduces mortality rates after acute deep venous thrombosis. These drugs seem to be as safe as unfractionated heparin with respect to major bleeding complications and appear to be as effective in preventing thromboembolic recurrences.
- Heparin, low-molecular weight
- Thrombophlebitis
- Meta-analysis
- Heparin
- Outcome and process assessment (health care)
Article and Author Information
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Acknowledgments: The authors thank Christopher Stave for assisting with the literature search and Ingram Olkin for thoughtfully reviewing a previous version of the manuscript.
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Grant Support: By grant HS00028-11 from the Agency for Health Care Policy and Research, Rockville, Maryland.
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Requests for Reprints: Michael K. Gould, MD, MSc, Pulmonary and Critical Care Medicine Section (111P), Veterans Affairs Palo Alto Health Care System, 3801 Miranda Avenue, Palo Alto, CA 94304; e-mail, gould{at}stanford.edu.
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Current Author Addresses: Dr. Gould: Pulmonary and Critical Care Section (111P), Veterans Affairs Palo Alto Health Care System, 3801 Miranda Avenue, Palo Alto, CA, 94304.
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Dr. Dembitzer: Department of Medicine, Veterans Affairs Palo Alto Health Care System, 3801 Miranda Avenue, Palo Alto, CA 94304.
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Dr. Doyle: Division of Pulmonary and Critical Care Medicine, Stanford University Medical Center, Stanford, CA 94305.
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Dr. Hastie: Department of Health Research and Policy, HRP Redwood Building, Stanford University Medical Center, Stanford, CA 94305.
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Dr. Garber: Center for Primary Care and Outcomes Research, Stanford University Medical Center, 30 Alta Road, Stanford, CA 94305.
- Copyright ©2004 by the American College of Physicians
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