Abstract
We evaluated whether a postoperative regimen with melagatran followed by oral ximelagatran, two new direct thrombin inhibitors, was an optimal regimen for thromboprophylaxis in major orthopaedic surgery. In a double-blind study, 2788 patients undergoing total hip or knee replacement were randomly assigned to receive for 8 to 11 days either 3 mg of subcutaneous melagatran started 4-12 h postoperatively, followed by 24 mg of oral ximelagatran twice-daily or 40 mg of subcutaneous enoxaparin once-daily, started 12 h preoperatively. Ximelagatran was to be initiated within the first two postoperative days. The primary efficacy endpoint was venous thromboembolism (deep-vein thrombosis detected by mandatory venography, pulmonary embolism or unexplained death). The main safety endpoint was bleeding. Venous thromboembolism occurred in 355/1146 (31.0%) and 306/1122 (27.3%) patients in the ximelagatran and enoxaparin group, respectively, a difference in risk of 3.7% in favour of enoxaparin (p = 0.053). Bleeding was comparable between the two groups.
Publication types
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Clinical Trial
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Comparative Study
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Multicenter Study
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Randomized Controlled Trial
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Research Support, Non-U.S. Gov't
MeSH terms
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Administration, Oral
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Adult
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Aged
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Aged, 80 and over
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Anticoagulants / administration & dosage
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Anticoagulants / adverse effects
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Anticoagulants / therapeutic use*
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Arthroplasty, Replacement, Hip*
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Arthroplasty, Replacement, Knee*
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Azetidines / administration & dosage
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Azetidines / adverse effects
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Azetidines / therapeutic use*
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Benzylamines
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Cause of Death
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Double-Blind Method
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Drug Administration Schedule
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Enoxaparin / administration & dosage
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Enoxaparin / adverse effects
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Enoxaparin / therapeutic use*
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Female
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Glycine / administration & dosage
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Glycine / adverse effects
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Glycine / analogs & derivatives*
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Glycine / therapeutic use*
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Hemorrhage / chemically induced
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Humans
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Injections, Subcutaneous
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Male
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Middle Aged
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Postoperative Complications / prevention & control*
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Prodrugs / administration & dosage
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Prodrugs / adverse effects
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Prodrugs / therapeutic use
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Prospective Studies
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Pulmonary Embolism / prevention & control*
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Safety
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Thrombin / antagonists & inhibitors*
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Treatment Outcome
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Venous Thrombosis / prevention & control*
Substances
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Anticoagulants
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Azetidines
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Benzylamines
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Enoxaparin
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Prodrugs
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melagatran
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ximelagatran
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Thrombin
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Glycine