Dabigatran Versus Lmwhs for Thromboprophylaxis after Total Hip or Knee Replacement

Summary

A Cochrane review [Abstract] 1 included 14 studies with a total of 21 642 subjects for efficacy and 27 360 for safety. Only patients subjected to elective total hip replacement (THR) or total knee replacement (TKR) were included but no patients with hip repair or hip fracture. Nine studies investigated ximelagatran, 4 oral dabigatran, and one subcutaneous desirudin. No difference was observed in major venous thromboembolism (VTE) in dabigatran compared with LMWH in total hip or knee replacement surgery (OR 0.98, 95% CI 0.74 to 1.29; 4 studies, n=7 664). No difference in total bleeding events (OR 1.02, 95% CI 0.83 to 1.24; 4 studies, n=10 084) or all-cause mortality (OR 1.56, 95% CI 0.63 to 3.90; 4 studies, n=10 036) were observed between dabigatran and LMWH.

A pooled analysis 2 of 3 studies with a total of 8 210 subjects compared dabigatran 220 mg or 150 mg once-daily with subcutaneous enoxaparin (40 mg once-daily or 30 mg twice-daily) for the primary prevention of venous thromboembolism (VTE) in patients undergoing elective total hip and knee arthroplasty. 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%) and 3.8% of the 150 mg group (RD vs. enoxaparin 0.5%, -0.6% to 1.6%). 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%) and 1.1% of the 150 mg group (RD vs. enoxaparin -0.4%, -1.0% to 0.2%).

A randomised, double-blind, non-inferioty study 3 included 2 055 subjects undergoing total hip arthroplasty, and compared 28-35 days treatment with oral dabigatran (220 mg once-daily, starting with a half-dose 1-4 hours after surgery) with subcutaneous enoxaparin 40 mg (once-daily, starting the evening before surgery). The primary efficacy outcome (a composite of total venous thromboembolism [VTE; venographic or symptomatic] and death from all-causes) occurred in 7.7% of the dabigatran group versus 8.8% of the enoxaparin group (risk difference, RD -1.1%, 95% CI -3.8 to 1.6%; p<0.0001 for the pre-specified non-inferiority margin). Major VTE (proximal deep-vein thrombosis or non-fatal pulmonary embolism) plus VTE-related death occurred in 2.2% of the dabigatran group versus 4.2% of the enoxaparin group (RD -1.9%, 95% CI -3.6% to -0.2%; p=0.03). Major bleeding occurred in 1.4% of the dabigatran group and 0.9% of the enoxaparin group (p=0.40).