undergoing total hip arthroplasty (THA) are in risky for developing venous

undergoing total hip arthroplasty (THA) are in risky for developing venous thromboembolism and for that reason require short-term prophylaxis with antithrombotic agencies. the event of bleeding complications or a need for urgent reversal. enoxaparin (= 0.051). Collectively data from the BISTRO studies established dabigatran 150 mg and 220 mg daily as the two most effective thrombopropylaxis dosages while maintaining a comparable safety profile to enoxaparin. The extended thromboembolism prevention after hip surgery (RE-NOVATE)[54] and RE-NOVATE BML-275 II[47] studies were randomized double-blind BML-275 non-inferiority Phase III studies of 3494 and 2055 patients respectively designed to evaluate the efficacy and safety of dabigatran compared to enoxaparin for VTE prophylaxis after THA (Table ?(Table3).3). RE-NOVATE randomized patients to either dabigatran 150 mg or 220 mg given orally once daily or enoxaparin 40 mg subcutaneously once daily. RE-NOVATE II focused solely on dabigatran 220 mg daily compared to enoxaparin. In each study dabigatran was started 1-4 h after surgery at a half-dose then continued at its full dose daily beginning post-operative day 1. Enoxaparin was started the evening before surgery and then continued once daily following surgery although the investigators did allow for enoxaparin to be initiated post-operatively Snr1 if consistent with local practice. Thromboprophylaxis was continued for either agent for 28-35 d. A primacy efficacy outcome of any VTE or all-cause mortality and a primary safety outcome of major bleeding during the treatment period were established. Both studies evaluated major VTE as defined by proximal DVT non-fatal PE or VTE-related death as a secondary outcome[47 54 Table 3 Phase III clinical trials of target specific oral anticoagulants (target BML-275 specific oral anticoagulants) The RE-NOVATE investigators found the incidence of primary efficacy outcome occurred in 8.6% (75/874) of dabigatran 150 mg 6 (53/880) of dabigatran 220 mg and 6.7% (60/897) of enoxaparin 40 mg patients respectively. Both doses of dabigatran achieved non-inferiority (< 0.0001) with no differences in the rates of major VTE for either dabigatran group compared to enoxaparin. Major and minor bleeding rates were also comparable between all groups[54]. RE-NOVATE II was focused solely on dabigatran 220 mg orally once daily compared to enoxaparin 40 mg subcutaneously daily. Results showed any VTE or death occurred in 7.7% (61/792) of dabigatran compared to 8.8% (69/785) of enoxaparin patients (= 0.43) establishing non-inferiority with dabigatran. There was however a significant difference in the rate of major VTE between dabigatran and enoxaparin (2.2% 4.2% = 0.03)[47]. Results of both RE-NOVATE and RE-NOVATE II studies demonstrated similar rates of major and minor bleeding between dabigatran and enoxaparin[47 54 A pooled analysis of phase III studies of orthopedic thromboprophylaxis (excluding RE-NOVATE II) found no differences in surgical site bleeding or wound contamination although smaller impartial investigations have since suggested a possible increased risk of post-operative wound complications with dabigatran BML-275 compared to LMWH[55 56 No incidence of spinal hematoma was observed in patients receiving both dabigatran and neuraxial anesthesia during three of four phase III studies (excluded RE-NOVATE II)[57]. As previously noted the risk of bleeding in Phase III studies of dabigatran in orthopedic surgery patients was not increased by concurrent..