Sent 6/24/07 DJ Quinlan, JW Eikelboom, JD Douketis. Anticoagulants (extended duration) for prevention of venous thromboembolism following total hip or knee replacement or hip fracture repair. The Cochrane Database of Systematic Reviews 2002:Art. No.: CD004179. DOI: 10.1002/14651858. (Protocol)

The control group for this review should not be the current standard of care. Prophylactic anticoagulation (regular duration: the control group) following total hip or knee replacement or hip fracture repair provides no survival benefit but does cause significant bleeding risk. In a meta-analysis of RCTs involving VTE prophylaxis of total hip replacement patients, the crude risks of clinically important bleeding (usually wound hematoma) were 0% for compression stockings, 0.3% for controls, 0.4% for aspirin, 1.8% for LMWH, and 2.6% for unfractionated heparin.¹ Because of the seriousness of wound hematomas and the frequently associated infections in these patients, the Scottish Intercollegiate Guidelines Network (SIGN) changed the hip fracture and hip and knee replacement surgical VTE prophylaxis guidelines from recommending anticoagulants to advising aspirin in 2002.² They based this change largely on an RCT of aspirin vs placebo in hip fracture and hip arthroplasty patients, which showed a reduction in FPE with aspirin comparable with that of anticoagulants,³ and a cohort study showing a lower than previously demonstrated rate of VTE in joint replacement patients treated with aspirin, mechanical leg compression, and leg exercises.⁴

Financial conflicts of interests of the authors have not been mentioned. As a member of the CORTES (Clivarin: Assessment of Regression of Thrombosis, Efficacy, and Safety) study group, Dr. Quinlan has received funding from Knoll Pharmaceuticals which makes reviparin (Clivarin®-a LMWH).⁵ He has received honoraria for speaking at symposia sponsored by pharmaceutical companies that market low-molecular-weight heparin preparations,⁶ including including Aventis, Sanofi-Synthelabo.⁷

Both Drs. Douketis and Eikelboom are research scholars of the Heart and Stroke Foundation of Canada. Anticoagulant producing drug company funders of this foundation include AstraZeneca Canada, Bayer, Boehringer Ingelheim Ltd./Ltée, Sanofi-Aventis, and Pfizer Canada Inc.⁸

Dr. Eikelboom has received honoraria for speaking at symposia sponsored by pharmaceutical companies that market low-molecular-weight heparin preparations,⁶ including including Aventis, Sanofi-Synthelabo and grants from Aventis and Sanofi-Synthelabo.⁷

1. Imperiale TF, Speroff T. A meta-analysis of methods to prevent venous thromboembolism following total hip replacement. JAMA. 1994;271(22):1780-1785.

2. Prophylaxis of Venous Thromboembolism. Scottish Intercollegiate Guidelines Network (SIGN) Publication No. 62. October 2002. Available at: http://www.sign.ac.uk/guidelines/fulltext/62/index.html. Accessed November 15, 2004.

3. Prevention of pulmonary embolism and deep vein thrombosis with low dose aspirin: Pulmonary Embolism Prevention (PEP) trial. Lancet. 2000;355(9212):1295-1302.

4. Sarmiento A, Goswami AD. Thromboembolic prophylaxis with use of aspirin, exercise, and graded elastic stockings or intermittent compression devices in patients managed with total hip arthroplasty. J Bone Joint Surg Am. 1999;81(3):339-346.

5. Breddin HK, Hach-Wunderle V, Nakov R, Kakkar VV. Effects of a Low-Molecular-Weight Heparin on Thrombus Regression of Recurrent Thromboembolism in Patients with Deep-Vein Thrombosis. The CORTES Investigators. New England Journal of Medicine. 2001;344(9):626-631.

6. Eikelboom JW, Quinlan DJ, Mehta SR, Turpie AG, Menown IB, Yusuf S. Unfractionated and Low-Molecular-Weight Heparin as Adjuncts to Thrombolysis in Aspirin-Treated Patients With ST-Elevation Acute Myocardial Infarction: A Meta-Analysis of the Randomized Trials. 0.1161/CIRCULATIONAHA.105.573550. Circulation. December 20, 2005;112(25):3855-3867.

7. Quinlan DJ, McQuillan A, Eikelboom JW. Low-Molecular-Weight Heparin Compared with Intravenous Unfractionated Heparin for Treatment of Pulmonary Embolism: A Meta-Analysis of Randomized, Controlled Trials. Ann Intern Med. February 3, 2004 2004;140(3):175-183.

8. The Heart and Stroke Foundation of Canada. Available at: http://ww2.heartandstroke.ca/Page.asp?PageID=1366&ArticleID=4803&Src=blank&From=SubCategory and http://ww2.heartandstroke.ca/images/english/HSFCAR05_Engweb.pdf. Accessed January 17, 2007.