Freedman KB, Brookenthal KR, Fitzgerald RH Jr, Williams S, Lonner JH.
A meta-analysis of thromboembolic prophylaxis following elective total hip
arthroplasty.
J Bone Surg Am 2000 Jul;82-A(7):929-38

Department of Orthopaedic Surgery, Center for Clinical Epidemiology and
Biostatistics, University of Pennsylvania School of Medicine, Philadelphia 19104,
USA. kfreedma@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).