Low-molecular-weight heparin prophylaxis using dalteparin in close proximity to surgery vs warfarin in hip arthroplasty patients - A double-blind, randomized comparison

Background: Based on the current understanding that venous thrombosis start s perioperatively, administration of just-in-time low-molecular-weight hepa rin immediately before or in close proximity after hip arthroplasty may be more effective than usual clinical practice. Methods: We performed a randomized, double-blind trial comparing subcutaneo us dalteparin sodium given once daily immediately before or early after sur gery with the use of postoperative warfarin sodium in 1472 patients undergo ing elective hip arthroplasties. The primary end point was deep vein thromb osis detected using contrast venography performed after surgery (mean, 5.7 days) in each group. Results: The frequencies of deep vein thrombosis for patients with interpre table venograms receiving preoperative and postoperative dalteparin for all deep vein thrombosis were 36 (10.7%) of 337 (P<.001) and 44 (13.1%) of 336 (P<.001), respectively, vs 81 (24.0%) of 338 for warfarin; for proximal de ep vein thrombosis, 3 (0.8%) of 354 (P=.04) and 3 (0.8%) of 358 (P=.03), re spectively, vs 11 (3.0%) of 363. Relative risk reductions for the daltepari n groups ranged from 45% to 72%. Symptomatic thrombi were less frequent in the preoperative dalteparin group (5/337 patients [1.5%]) vs the warfarin g roup (15/338 patients [4.4%]) (P=.02). Serious bleeding was similar among g roups. Increased major bleeding at the surgical site was observed for patie nts receiving preoperative dalteparin vs warfarin (P=.01). Conclusions: A modified dalteparin regimen in close proximity to surgery re sulted in substantive risk reductions for all and proximal deep vein thromb osis, compared with warfarin therapy. Such findings have not been observed with low-molecular-weight heparin therapy commenced 12 hours preoperatively or 12 to 24 hours postoperatively vs oral anticoagulants. Increased major but not serious bleeding occurred in patients receiving preoperative daltep arin. Dalteparin therapy initiated postoperatively provided superior effica cy vs warfarin without significantly increased overt bleeding.