Comparison of Ximelagatran with Warfarin for the Prevention of Venous Thromboembolism after Total Knee Replacement

Francis, Charles W.; Berkowitz, Scott D.; Lieberman, Jay R.; Ginsberg, Jeffrey S.; Paiement, Guy D.; Peters, Gary; Roth, Anne W.; McElhattan, Jennifer; Colwell, Clifford W.

doi:10.1056/nejmoa035162

Cited by 288 publications

(106 citation statements)

References 30 publications

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“…In the PEGASUS trial, which included 2,048 patients undergoing high-risk abdominal surgery, postoperative fondaparinux (2.5 mg once daily) was shown to be as effective and as safe as perioperative dalteparin (5,000 IU once daily). 36 Ximelagatran, an orally administered direct thrombin inhibitor, has shown promise as a prophylactic agent in orthopedic 37 and abdominal 38 surgery based on preliminary results, but it was refused approval by the FDA in September 2004 because of concerns about liver toxicity. 39 The company has withdrawn the substance but other thrombin inhibitors are on the way.…”

Section: Pharmacologic Prophylaxismentioning

confidence: 99%

Venous Thromboembolism: A Review of Risk and Prevention in Colorectal Surgery Patients

Bergqvist

2006

Diseases of the Colon &Amp; Rectum

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Hospitalization for surgery has a high risk of developing venous thromboembolism, a condition that encompasses both deep-vein thrombosis and its potentially fatal complication, pulmonary embolism. Colorectal surgery implies a specific high risk for postoperative thromboembolic complications relative to other general surgery. This may be a result of pelvic dissection, the perioperative positioning of these patients, or the presence of additional risk factors common to this patient group, such as cancer, advanced age, or inflammatory bowel disease. The potential impact of venous thromboembolism and the need for effective thromboprophylaxis often are underestimated in these patients. Recommendations for thromboprophylaxis in colorectal surgery patients are based on the American College of Chest Physicians guidelines for thrombosis prevention in general surgery patients, with treatment stratified according to the type of surgery and additional venous thromboembolism risk factors present. Prophylaxis with low-molecular-weight heparin or unfractionated heparin is recommended for colorectal surgery patients classified as moderate to high risk. The small number of studies focusing specifically on colorectal patients, or on cancer or abdominal surgery patients with a colorectal subgroup, has shown that both low-molecular-weight heparin and unfractionated heparin can effectively reduce the incidence of venous thromboembolism. Low-molecular-weight heparin has the practical advantage of once-daily administration and shows a lower risk of heparin-induced thrombocytopenia. This review will assess the risk of venous thromboembolism in colorectal surgery patients and discuss current evidence-based guidelines and recommendations for prevention of venous thromboembolism.

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Section: Pharmacologic Prophylaxismentioning

confidence: 99%

Venous Thromboembolism: A Review of Risk and Prevention in Colorectal Surgery Patients

Bergqvist

2006

Diseases of the Colon &Amp; Rectum

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“…Although clinical trials showed that ximelagatran, the first oral direct thrombin inhibitor to be developed, is an effective anticoagulant for many clinical indications [19][20][21][22], it was withdrawn from the market by the manufacturer in February 2006 [23] because of fears of liver toxicity. There are, however, other direct thrombin inhibitors that are under development and will appear in its wake.…”

Section: Discussionmentioning

confidence: 99%

Vitamin K deficiency amplifies anticoagulation response to ximelagatran: possible implications for direct thrombin inhibitors and their clinical safety

2008

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“…Dependence on AT to achieve an anticoagulant effect has been overcome, however, by the development of direct thrombin inhibitors (DTIs). One such agent is the novel oral DTI ximelagatran, which is currently undergoing clinical evaluation for the prevention and treatment of thromboembolic disorders [25][26][27]. Following oral administration, ximelagatran is rapidly absorbed and bioconverted to its active form melagatran which, unlike UH and low-molecular-weight heparin (LMWH), provides competitive, direct inhibition of both free and clot-bound thrombin [12,28].…”

Section: Discussionmentioning

confidence: 99%

Drotrecogin Alfa (activated, Xigris�) in Combination with Heparin or Melagatran: An In vitro Investigation

Koestenberger

Cvirn

Gallistl

et al. 2004

J Thromb Thrombolysis

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Comparison of Ximelagatran with Warfarin for the Prevention of Venous Thromboembolism after Total Knee Replacement

Abstract: The efficacy of oral ximelagatran, administered starting the morning after total knee replacement, was superior to that of warfarin for prevention of venous thromboembolism. Rates of hemorrhagic complications with the two drugs were similar.

Cited by 288 publications

References 30 publications

Venous Thromboembolism: A Review of Risk and Prevention in Colorectal Surgery Patients

Venous Thromboembolism: A Review of Risk and Prevention in Colorectal Surgery Patients

Vitamin K deficiency amplifies anticoagulation response to ximelagatran: possible implications for direct thrombin inhibitors and their clinical safety

Drotrecogin Alfa (activated, Xigris�) in Combination with Heparin or Melagatran: An In vitro Investigation

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