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Efficacy and Cost of Low-Molecular-Weight Heparin Compared with Standard Heparin for the Prevention of Deep Vein Thrombosis after Total Hip Arthroplasty

David R. Anderson, MD; Bernie J. O'Brien, PhD; Mark N. Levine, MD; Robin Roberts, MSc; Philip S. Wells, MD; and Jack Hirsh, MD
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From McMaster University and the Hamilton Civic Hospitals Research Centre, Hamilton, Ontario. Requests for Reprints: David Anderson, MD, Room 132, West Wing, Mackenzie Building, 5578 University Avenue, Halifax, Nova Scotia, Canada B3H 1Y8. Acknowledgment: The authors thank Mrs. Debbie Redshaw for data collection. Grant Support: Dr. Anderson was a Research Fellow with the Canadian Heart and Stroke Foundation when this study was done. Dr. Levine is a Career Scientist with the Medical Research Council of Canada. Dr. Wells is the recipient of a McLaughlin fellowship from the University of Ottawa. Dr. Hirsh is a Distinguished Professor of the Ontario Heart and Stroke Foundation.

Copyright 2004 by the American College of Physicians

Ann Intern Med. 1993;119(11):1105-1112. doi:10.7326/0003-4819-119-11-199312010-00008
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Purpose: To compare the efficacy, safety, and cost-effectiveness of low-molecular-weight heparin with standard heparin for the prevention of deep vein thrombosis after total hip arthroplasty.

Data Identification: Studies were identified by MEDLINE search and review of bibliographies of retrieved articles. Hospital resources used in treating deep vein thrombosis and bleeding complications after total hip arthroplasty were estimated using retrospectively collected data from 447 patients who participated in a recently completed randomized, controlled deep vein thrombosis prophylaxis trial at our center.

Study Selection: randomized, controlled trials directly comparing a low-molecular-weight heparin preparation with standard heparin for the prevention of deep vein thrombosis after total hip arthroplasty were potentially eligible for the meta-analysis.

Data Extraction: Data from eligible studies were extracted independently by two of the authors. Multiple regression analysis of data from the patient cohort was used to estimate the effect of deep vein thrombosis and bleeding on length of hospital stay. A hypothetical North American price for low-molecular-weight heparin was determined based on the ratio between low-molecular-weight heparin and standard heparin in France. Costs were based on weighted per-diem hospital expenditures and physician fees for procedures and reported in 1992 U.S. dollars.

Results of Data Synthesis: Meta-analysis of six eligible trials determined that low-molecular-weight heparin was significantly more effective than standard heparin at preventing deep vein thrombosis after total hip arthroplasty (common odds ratio, 0.72; 95% CI, 0.53 to 0.95). However, this benefit was restricted to the prevention of proximal deep vein thrombosis (common odds ratio, 0.40; CI, 0.28 to 0.59). No significant differences were found in the rates of distal deep vein thrombosis or total, major, or minor bleeding between the two groups. Based on a 2.6 to 1 price ratio between low-molecular-weight heparin and standard heparin, use of low-molecular-weight heparin would save the health care system about $50 000 per 1000 patients treated. Sensitivity analysis shows that if the low-molecular-weight heparin/standard heparin price ratio exceeds 3.7 (the threshold value lies between 0.8 and 5.5 based on the extremes of the 95% CI of the common odds ratios for deep vein thrombosis and bleeding complications), use of low-molecular-weight heparin is more expensive. At a price ratio of 10, it would cost more than $250 000 to treat 1000 patients with low-molecular-weight heparin compared with standard heparin or about $5000 for each additional deep vein thrombosis prevented with low-molecular-weight heparin.

Conclusions: Low-molecular-weight heparin is more effective and is at least as safe as standard heparin for the prevention of deep vein thrombosis after total hip arthroplasty. Based on the current French price ratio of low-molecular-weight heparin to standard heparin, the use of low-molecular-weight heparin in North America would result in overall savings in cost; however, the relative cost-effectiveness is critically dependent on the price ratio between the two drugs. Further research is needed to compare the cost-effectiveness of low-molecular-weight heparin with other prophylactic regimens and postoperative deep vein thrombosis management strategies.


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Figure 1.
Cost difference over range of price ratios.

Difference in total cost of managing 1000 patients with low-molecular-weight heparin compared with standard heparin after total hip arthroplasty over a range of low-molecular-weight heparin/standard heparin ratios. Negative dollars indicate cost saving for use of low-molecular-weight heparin. Sensitivity range represents the variation in costs over the 95% CI of the common odds ratio for deep vein thrombosis and bleeding.

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