Direct thrombin inhibitor melagatran followed by oral ximelagatran in comparison with enoxaparin for prevention of venous thromboembolism after total hip or knee replacement.
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.
Eriksson
Bengt I
BI
Orthopaedics Department, Sahlgrenska University Hospital/OSTRA, Göteborg, Sweden. b.eriksson@orthop.gu.se
Agnelli
Giancarlo
G
Cohen
Alexander T
AT
Dahl
Ola E
OE
Mouret
Patrick
P
Rosencher
Nadia
N
Eskilson
Christina
C
Nylander
Ingela
I
Frison
Lars
L
Ogren
Mats
M
D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000925:Anticoagulants / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D019644:Arthroplasty, Replacement, Hip; D019645:Arthroplasty, Replacement, Knee; D001384:Azetidines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001596:Benzylamines; D002423:Cause of Death; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D017984:Enoxaparin / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D005998:Glycine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D006470:Hemorrhage / Q000139:chemically induced; D006801:Humans; D007279:Injections, Subcutaneous; D008297:Male; D008875:Middle Aged; D011183:Postoperative Complications / Q000517:prevention & control*; D011355:Prodrugs / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D011446:Prospective Studies; D011655:Pulmonary Embolism / Q000517:prevention & control*; D012449:Safety; D013917:Thrombin / Q000037:antagonists & inhibitors*; D016896:Treatment Outcome; D020246:Venous Thrombosis / Q000517:prevention & control*
D000925:Anticoagulants; D001384:Azetidines; D001596:Benzylamines; D017984:Enoxaparin; D011355:Prodrugs; C109573:melagatran; C426686:ximelagatran; D013917:Thrombin; D005998:Glycine