The Journal of Bone and Joint Surgery 82:929 (2000)
© 2000 The Journal of Bone and Joint Surgery, Inc.
A Meta-Analysis of Thromboembolic Prophylaxis Following Elective Total Hip Arthroplasty*
Kevin B. Freedman, M.D., M.S.C.E. ,
Keith R. Brookenthal, M.D. ,
Robert H. Fitzgerald, Jr, M.D. ,
Sankey Williams, M.D. and
Jess H. Lonner, M.D.
Investigation performed at the University of Pennsylvania
School of Medicine, Philadelphia, Pennsylvania
*No benefits in any form have been received or will be received
from a commercial party related directly or indirectly to the subject
of this article. No funds were received in support of this study.
Department of Orthopaedic Surgery (K. B. F., K. R. B., R. H.
F., Jr., and J. H. L.), Division of General Internal Medicine (S.
W.), Center for Clinical Epidemiology and Biostatistics (K. B. F.
and S. W.), and Department of Biostatistics and Epidemiology (K.
B. F. and S. W.), University of Pennsylvania School of Medicine,
2 Silverstein Pavilion, 3400 Spruce Street, Philadelphia, Pennsylvania 19104.
E-mail address for K. B. Freedman: kfreedma{at}mail.med.upenn.edu
Background: Although several agents have
been shown to reduce the risk of thromboembolic disease, there is no
clear preference for thromboembolic prophylaxis in elective total
hip arthroplasty. The purpose of this study was to define the efficacy
and safety of the agents that are currently used for prophylaxis
against deep venous thrombosis - namely, low-molecular-weight heparin,
warfarin, aspirin, low-dose heparin, and pneumatic compression.
Methods: A Medline search identified all randomized,
controlled trials, published from January 1966 to May 1998, that
compared the use of one of the prophylactic agents with the use
of any other agent or a placebo in patients undergoing elective
total hip arthroplasty. For a study to be included in our analysis,
bilateral venography had to have been performed to confirm the presence
or absence of deep venous thrombosis. Fifty-two studies, in which 10,929
patients had been enrolled, met the inclusion criteria and were
included in the analysis. The rates of distal, proximal, and total
(distal and proximal) deep venous thrombosis; symptomatic and fatal
pulmonary embolism; minor and major wound-bleeding complications;
major non-wound bleeding complications; and total mortality were determined
for each agent in each study. The absolute risk of each outcome
was determined by dividing the number of events by the number of patients
at risk. A general linear model with random effects was used to
calculate the 95 percent confidence interval of risk. A crosstabs
of study by outcome was performed to test homogeneity (ability to
combine studies). The risk of each outcome was compared among agents
and between each agent and the placebo.
Results: With prophylaxis, the risk of total
(proximal and distal) deep venous thrombosis ranged from 17.7 percent
(low-molecular-weight heparin) to 31.1 percent (low-dose heparin);
the risk with prophylaxis with any agent was significantly lower
than the risk with the placebo (48.5 percent) (p < 0.0001).
The risk of proximal deep venous thrombosis was lowest with warfarin
(6.3 percent) and low-molecular-weight heparin (7.7 percent), and again
the risk with any prophylactic agent was significantly lower than
the risk with the placebo (25.8 percent) (p < 0.0001). Compared
with the risk with the placebo (1.51 percent), only warfarin (0.16
percent), pneumatic compression (0.26 percent), and low-molecular-weight
heparin (0.36 percent) were associated with a significantly lower risk
of symptomatic pulmonary embolism. There were no significant differences
among agents with regard to the risk of fatal pulmonary embolism
or of mortality with any cause. The risk of minor wound-bleeding
was significantly higher with low-molecular-weight heparin (8.9
percent) and low-dose heparin (7.6 percent) than it was with the placebo
(2.2 percent) (p < 0.05). Compared with the risk with the placebo
(0.28 percent), only low-dose heparin was associated with a significantly higher
risk of major wound-bleeding (2.56 percent) and total major bleeding
(3.46 percent) (p < 0.0001).
Conclusions: The best prophylactic agent in
terms of both efficacy and safety was warfarin, followed by pneumatic
compression, and the least effective and safe was low-dose heparin.
Warfarin provided the lowest risk of both proximal deep venous thrombosis and
symptomatic pulmonary embolism. However, there were no identifiable
significant differences in the rates of fatal pulmonary embolism
or death among the agents. Significant risks of minor and major
bleeding complications were observed with greater frequency with
certain prophylactic agents, particularly low-molecular-weight heparin (minor
bleeding) and low-dose heparin (both major and minor bleeding).

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