Review: Low-molecular-weight heparin or standard heparin for deep vein thrombosis after total hip arthroplasty
ACP J Club. 1994 May-June;120:71. doi:10.7326/ACPJC-1994-120-3-071
Abstract title formerly "Low-Molecular-Weight Heparin or Standard Heparin for Deep Vein Thrombosis: A Meta-Analysis." Anderson DR, O'Brien BJ, Levine MN, et al. Efficacy and cost of low-molecular-weight heparin compared with standard heparin for the prevention of deep vein thrombosis after total hip arthroplasty. Ann Intern Med. 1993 Dec 1;119:1105-12.
To compare the efficacy, safety, and cost-effectiveness of low-molecular-weight (LMW) heparin with standard heparin for the prevention of deep vein thrombosis (DVT) after total hip arthroplasty, using meta-analysis.
Studies were identified by searching MEDLINE using the key words venous thrombosis, hip arthroplasty, and heparin. Additional studies were identified by scanning the bibliographies of retrieved articles and by reviewing abstracts from recent meetings. The hospital resource consequences of DVT and bleeding were estimated using data from 447 inpatients managed at a Hamilton, Ontario, hospital.
Studies were selected if they were randomized controlled trials directly comparing LMW heparin with standard heparin for the prevention of DVT (determined by blinded venogram interpretation) after hip arthroplasty. Studies were excluded if the dose of the study drugs was other than that recommended by the manufacturer.
2 investigators independently extracted data on total DVT, bleeding complications, and symptomatic pulmonary embolism. Trial results were combined using the Mantel-Haenszel common odds ratio method. A price for LMW heparin was estimated based on prices in France. Costs were based on weighted per diem hospital expenditures and on physician fees for procedures.
6 trials met the selection criteria. LMW heparin was more effective than standard heparin in preventing DVT (common odds ratio [OR] 0.72, 95% CI 0.53 to 0.95). This benefit was greatest for prevention of proximal DVT (OR 0.40, CI 0.28 to 0.59). No significant differences were found for total, major, or minor bleeding. Based on a 2.6 to 1 price ratio between LMW heparin and standard heparin, use of LMW heparin would save about $50 000 per 1000 patients treated. If the price ratio exceeded 3.7, use of LMW heparin would be more expensive.
Low-molecular-weight heparin was more effective and at least as safe as standard heparin for the prevention of deep vein thrombosis after total hip arthroplasty. Based on the French price ratio of low-molecular-weight heparin to standard heparin, use of low-molecular-weight heparin in North America would result in overall cost savings.
Sources of funding: Canadian Heart and Stroke Foundation; Medical Research Council of Canada; Ontario Heart and Stroke Foundation.
For article reprint: Not available.
The incidence of DVT may be as high as 50% in patients having total hip arthroplasty and even higher after major knee surgery. Accordingly, there is considerable interest in prophylaxis for DVT in patients having these procedures. Based on a review of randomized trials, low-dose treatment with warfarin (INR, 2.0 to 3.0) was recommended as the most effective anticoagulant regimen for prophylaxis by the American College of Chest Physicians' Third Consensus Conference on Antithrombotic Therapy (1).
The study by Hull and colleagues suggests that treatment with a LMW heparin (Logiparin; Novo Nordisk Pharmaceuticals Inc.), administered as a single daily subcutaneous injection, may be slightly more effective than low-dose warfarin but is associated with a slightly higher incidence of bleeding. Logiparin and other LMW heparins have a high degree of bioavailability and a long half-life. A slightly greater benefit may also occur using LMW heparin compared with warfarin in patients having knee surgery. Overall, Logiparin reduced the incidence of proximal DVT by 1.5% and of distal thrombosis by 4.5%, albeit with a 1.6% increase in risk for major bleeding episodes.
The review by Anderson and colleagues concluded that LMW heparins were potentially more cost-effective than unfractionated heparins (administered subcutaneously twice daily) based on an analysis of the cost of managing patients with DVT and bleeding complications. In their meta-analysis comparing the 2 types of heparin, a 7% reduction occurred in the incidence of proximal DVT using LMW heparin but no difference occurred in the incidence of distal DVT or in the rates of major or minor bleeding. Anderson and colleagues suggest that if LMW heparin costs 2.6 times as much as standard unfractionated heparin (administered subcutaneously twice daily), the increased cost is offset by the decreased number of patients who require treatment for proximal DVT. Applying the costs calculated by Anderson and colleagues for managing DVT and major bleeding complications to the study by Hull and colleagues, it is unlikely that LMW heparin is more cost-effective than low-dose warfarin because the cost of the increase in major bleeding complications with Logiparin would diminish the benefit of a decrease in the number of patients requiring treatment for DVT. Further, Anderson and colleagues suggest that LMW heparins are cost-effective based on an increased price of only 2.6 times that of unfractionated heparin. Enoxaparin (Lovenox, Rhône-Poulenc), the first LMW heparin to be approved in the United States for prophylaxis of DVT after hip replacement, was introduced at an average wholesale price of $23/d (2). This is considerably more than the cost of subcutaneous heparin twice daily in most U.S. hospitals or the cost of low-dose warfarin. Thus, treatment with LMW heparins appears to offer greater protection from DVT after total hip or knee arthroplasty than does subcutaneous administration of unfractionated heparin, and may be equivalent to the preferred regimen of low-dose warfarin prophylaxis, but at a greater cost.
Paul Eisenberg, MD
Washington University School of Medicine St. Louis, Missouri, USA