Oral thrombin inhibitor dabigatran etexilate vs North American enoxaparin regimen for prevention of venous thromboembolism after knee arthroplasty surgery.
Dabigatran, an oral once-daily unmonitored thrombin inhibitor, has been tested elsewhere using enoxaparin 40 mg once daily. We used the North American enoxaparin 30 mg BID regimen as the comparator. This was a double-blind, centrally randomized trial. Unilateral total knee arthroplasty patients were randomized to receive oral dabigatran etexilate 220 or 150 mg once daily, or enoxaparin 30 mg SC BID after surgery, blinded. Dosing stopped at contrast venography, 12 to 15 days after surgery. Among 1896 patients, dabigatran 220 and 110 mg showed inferior efficacy to enoxaparin (venous thromboembolism rates of 31% [P = .02 vs enoxaparin], 34% [P < .001 vs enoxaparin], and 25%, respectively). Bleeding rates were similar, and no drug-related hepatic illness was recognized. Dabigatran, effective compared to once-daily enoxaparin, showed inferior efficacy to the twice-daily North American enoxaparin regimen, probably because of the latter's more intense and prolonged dosing.
McMaster University Medical Centre, Ontario, Canada.
Ginsberg
Jeffrey S
JS
Davidson
Bruce L
BL
Comp
Philip C
PC
Francis
Charles W
CW
Friedman
Richard J
RJ
Huo
Michael H
MH
Lieberman
Jay R
JR
Muntz
James E
JE
Raskob
Gary E
GE
Clements
Mary L
ML
Hantel
Stefan
S
Schnee
Janet M
JM
Caprini
Joseph A
JA
D000284:Administration, Oral; D000368:Aged; D000925:Anticoagulants / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D019645:Arthroplasty, Replacement, Knee / Q000009:adverse effects*; D001562:Benzimidazoles / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000069604:Dabigatran; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D017984:Enoxaparin / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D005060:Europe; D005260:Female; D006801:Humans; D007279:Injections, Subcutaneous; D008297:Male; D008875:Middle Aged; D009656:North America; D017063:Outcome Assessment, Health Care; D011725:Pyridines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D012307:Risk Factors; D013917:Thrombin / Q000037:antagonists & inhibitors*; D054556:Venous Thromboembolism / Q000209:etiology / Q000517:prevention & control*
D000925:Anticoagulants; D001562:Benzimidazoles; D017984:Enoxaparin; D011725:Pyridines; D013917:Thrombin; D000069604:Dabigatran