Dabigatran versus enoxaparin for prevention of venous thromboembolism after hip or knee arthroplasty: a pooled analysis of three trials.
BACKGROUND
Three randomized, double-blind trials compared dabigatran, an oral direct thrombin inhibitor, with enoxaparin for the primary prevention of venous thromboembolism (VTE) in patients undergoing elective total hip and knee arthroplasty.


OBJECTIVE
We conducted a pre-specified pooled analysis of these trials. 8,210 patients were randomized, of whom 8,135 were treated (evaluable for safety) with dabigatran 220 mg or 150 mg once-daily, or subcutaneous enoxaparin (40 mg once-daily or 30 mg twice-daily). Efficacy analyses were based on the modified intention-to-treat population of 6,200 patients with an evaluable outcome. The common risk difference (RD) of treatment effect between each dabigatran dose and enoxaparin was estimated using fixed-effects models, and statistical heterogeneity was estimated using the I2 statistic.


RESULTS
The composite outcome of major VTE (proximal deep vein thrombosis and/or pulmonary embolism) and VTE-related mortality occurred in 3.3% of the enoxaparin group versus 3.0% of the dabigatran 220 mg group (RD vs. enoxaparin -0.2%, 95% CI -1.3% to 0.9%, I2=37%) and 3.8% of the 150 mg group (RD vs. enoxaparin 0.5%, -0.6% to 1.6%, I2=0%). Major bleeding occurred in 1.4% of the enoxaparin group versus 1.4% of the dabigatran 220 mg group (RD vs. enoxaparin -0.2%, -0.8% to 0.5%, I2=40%) and 1.1% of the 150 mg group (RD vs. enoxaparin -0.4%, -1.0% to 0.2%, I2=0%).


CONCLUSIONS
Oral dabigatran was as effective as subcutaneous enoxaparin in reducing the risk of major VTE and VTE-related mortality after hip or knee arthroplasty and has a similar bleeding profile.
Friedman
R J
RJ
Medical University of South Carolina and Charleston Orthopedic Associates, Charleston, South Carolina 29414, USA. rjfriedman@mybones.com
Dahl
O E
OE
Rosencher
N
N
Caprini
J A
JA
Kurth
A A
AA
Francis
C W
CW
Clemens
A
A
Hantel
S
S
Schnee
J M
JM
Eriksson
B I
BI
D000284:Administration, Oral; D000368:Aged; D019644:Arthroplasty, Replacement, Hip / Q000009:adverse effects* / Q000401:mortality; D019645:Arthroplasty, Replacement, Knee / Q000009:adverse effects* / Q000401:mortality; D001562:Benzimidazoles / Q000008:administration & dosage* / Q000009:adverse effects; D016009:Chi-Square Distribution; D000069604:Dabigatran; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D017558:Elective Surgical Procedures; D017984:Enoxaparin / Q000008:administration & dosage* / Q000009:adverse effects; D019317:Evidence-Based Medicine; D005260:Female; D005343:Fibrinolytic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D006470:Hemorrhage / Q000139:chemically induced; D006801:Humans; D007279:Injections, Subcutaneous; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D011725:Pyridines / Q000008:administration & dosage* / Q000009:adverse effects; D016032:Randomized Controlled Trials as Topic; D018570:Risk Assessment; D012307:Risk Factors; D016896:Treatment Outcome; D054556:Venous Thromboembolism / Q000209:etiology / Q000401:mortality / Q000517:prevention & control*
D001562:Benzimidazoles; D017984:Enoxaparin; D005343:Fibrinolytic Agents; D011725:Pyridines; D000069604:Dabigatran