Ximelagatran (Exantra®, AstraZeneca), an oral direct thrombin inhibitor, is an effective change of pace from warfarin, a commonly used anticoagulant, according to a 74-hospital study of 680 patients who had undergone total knee arthroplasty.
After seven to 12 days of treatment, the incidence of venous thromboembolism (measured by central adjudication) was 19% in patients taking ximelagatran and 26% in those taking warfarin. On local assessment, the incidence was 25% with ximelagatran and 34% with warfarin. Major bleeding was rare, affecting only 1.7% of patients taking ximelagatran and 0.9% of those taking warfarin.
Unlike canadian warfarin, ximelagatran does not call for monitoring or dose adjustment. Drug interactions, diet, concomitant disease, and varying metabolisms all influence the utilization of warfarin, the researchers explain. Warfarin also has a delayed onset and does not achieve the target anticoagulant level until at least the third postoperative day—a problem in orthopedic surgery, when thrombosis may start on the first day. Ximelagatran is rapidly absorbed and converted to its active form, melagatran, which acts directly on throm-bin and is eliminated unmetabolized through the kidneys.
In fixed doses, ximelagatran produces predictable plasma melagatran concentrations and produces no known food or drug interactions, the researchers say, although plasma concentrations are influenced by renal function and the patient’s weight. Animal studies have indicated that ximelagatran has a wide therapeutic window and increases bleeding only slightly at therapeutic doses.
Because wound healing is a concern when antithrombotic therapy is used, the researchers also analyzed complications at the surgical site but observed no differences between the two groups.