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Original Research: ANTITHROMBOTIC THERAPY |

Dosing Frequency of Unfractionated Heparin ThromboprophylaxisDosing Unfractionated Heparin Thromboprophylaxis: A Meta-analysis

Olivia J. Phung, PharmD; Susan R. Kahn, MD; Deborah J. Cook, MD, MSc(Epi); Mohammad Hassan Murad, MD, MPH
Author and Funding Information

From the College of Pharmacy (Dr Phung), Western University of Health Sciences, Pomona, CA; Department of Medicine (Dr Kahn), McGill University, Montreal, QC, Canada; Departments of Medicine, Clinical Epidemiology, and Biostatistics (Dr Cook), McMaster University, Hamilton, ON, Canada; and Division of Preventive Medicine and Knowledge and Evaluation Research Unit (Dr Murad), Mayo Clinic, Rochester, MN.

Correspondence to: Olivia J. Phung, PharmD, College of Pharmacy, Western University of Health Sciences, 309 E Second St, Pomona, CA 91766; e-mail: ophung@westernu.edu


Funding/Support: The authors have reported to CHEST that no funding was received for this study.

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (http://www.chestpubs.org/site/misc/reprints.xhtml).


Chest. 2011;140(2):374-381. doi:10.1378/chest.10-3084
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Background:  In medical patients, it is unclear whether thromboprophylaxis with low-dose unfractionated heparin (UFH) should be administered bid or tid.

Methods:  This study was a mixed-treatment comparison meta-analysis of randomized control trials that enrolled hospitalized nonsurgical patients at risk for VTE and compared UFH bid, UFH tid, or low-molecular-weight heparin (LMWH) to one another or to an inactive control subject. DVT, pulmonary embolism (PE), major bleeding, and death were measured. A Bayesian framework using a random-effects model was applied.

Results:  Sixteen trials with moderate methodologic quality enrolling 27,667 patients contributed to this analysis. The relative risk and 95% credible intervals comparing UFH tid to UFH bid for DVT, PE, death, and major bleeding were 1.56 (0.64-4.33), 1.67 (0.49-208.09), 1.17 (0.72-1.95), and 0.89 (0.08-7.05), respectively. When compared with either dose of UFH, the use of LMWH has an effect similar to UFH on all four outcomes.

Conclusions:  Moderate-quality evidence suggests that subcutaneous UFH bid and UFH tid do not differ in effect on DVT, PE, major bleeding, and mortality. Either of the two dosing regimens of UFH or LMWH appears to be a reasonable strategy for thromboprophylaxis in medical patients. A future randomized trial comparing the two doses of UFH is very unlikely, considering the very large sample size that would be required to demonstrate a significant difference, which, if it exists, is undoubtedly small.

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