A Comparison of Subcutaneous Low-Molecular-Weight Heparin with Warfarin Sodium for Prophylaxis against Deep-Vein Thrombosis after Hip or Knee Implantation

Russell Hull, Gary Raskob, Graham Pineo, David Rosenbloom, William Evans, Thomas Mallory, Kenneth Anquist, Frank Smith, Gary Hughes, David Green, C. Gregory Elliott, Akbar Panju, Rollin Brant

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Deep-vein thrombosis is a potentially life-threatening complication of total hip or knee replacement. There are few data on the effectiveness and safety of warfarin as compared with low-molecular-weight heparin as prophylaxis against this problem. We therefore performed a randomized, double-blind trial in 1436 patients to evaluate the effectiveness and safety of low-molecular-weight heparin (given subcutaneously once daily) as compared with adjusted-dose warfarin to prevent venous thrombosis after hip or knee replacement. Treatment with the drugs was started postoperatively. The primary end point was deep-vein thrombosis as detected by contrast venography (performed a mean of 9.4 days after surgery in each group). Among the 1207 patients with interpretable venograms, 231 of 617 patients (37.4 percent) in the warfarin group and 185 of 590 patients (31.4 percent) in the low-molecular-weight-heparin group had deep-vein thrombosis (P = 0.03). The reduction in risk with low-molecular-weight heparin as compared with warfarin was 16 percent, and the absolute difference in the incidence of venous thrombosis was 6 percent in favor of low-molecular-weight heparin (95 percent confidence interval, 0.8 to 11.4 percent). The incidence of major bleeding was 1.2 percent (9 of 721 patients) in the warfarin group and 2.8 percent (20 of 715 patients) in the low-molecular-weight-heparin group (P = 0.04), and the absolute difference was 1.5 percent in favor of warfarin (95 percent confidence interval, 0.1 to 3.0 percent). Our data demonstrate that the small reduction in the incidence of venous thrombosis with low-molecular-weight heparin, as compared with warfarin, was offset by an increase in bleeding complications. Although the use of low-molecular-weight heparin is simpler, because it is administered subcutaneously without the need for monitoring, it may be more costly than warfarin. Warfarin is inexpensive, but the overall cost of its use is increased by the need to monitor the intensity of anticoagulation. At this time it is unclear which of these approaches is the most cost effective., Postoperative deep-vein thrombosis presents a major clinical threat to patients undergoing hip or knee replacement14. In the absence of prophylactic anticoagulation, this disorder occurs in 40 to 60 percent of patients receiving hip implants59 and in 60 to 70 percent of patients receiving knee implants1012. Several approaches to prevention are accepted in North America1: less intense warfarin sodium (international normalized ratio, 2.0 to 3.0),1316 pneumatic compression,10,11,1418 and subcutaneous heparin1921. Less intense prophylaxis with warfarin sodium has been recommended as a standard by the National Heart, Lung, and Blood…

Original languageEnglish (US)
Pages (from-to)1370-1376
Number of pages7
JournalNew England Journal of Medicine
Issue number19
StatePublished - Nov 4 1993

ASJC Scopus subject areas

  • Medicine(all)


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