s 24%. Signifi cant dose dependent decrease in VTE with increasing doses of dabigatran etexilate Major bleeding: 0.3% vs 2.0% RE NOVATE III THR 220 and 150 mg od Enoxaparin Composite of VTE and all cause mortality Bleeding events Primary endpoint: 8.6% and 6.0% vs 6.7% Major bleeding: 2.0% and 1.3% vs 1.6% RE MODEL III TKR 220 and 150 mg od Enoxaparin Composite of VTE and all cause KU-55933 mortality Major bleeding Primary endpoint: 40.5% and 36.4% vs 37.7% Major bleeding: 1.3% and 1.5% vs 1.3% RE MOBILIZE III TKR 220 and 150 mg od Enoxaparin Composite of VTE and all cause mortality Major bleeding Primary endpoint: 33.7%, 31.1% vs 25.3% Major bleeding: 0.6% and 0.6% vs 1.
4% Rivaroxaban ODIXa HIP ODIXa HIP2 ODIXa KNEE ODIXa OD HIP II II II II THR THR TKR THR NPI-2358 5 60 mg bid/od 5 60 mg bid 5 60 mg bid 5 40 mg od Enoxaparina Composite of objective DVT, symptomatic PE, and all cause mortality Major bleeding No signifi cant dose response for effi cacy, total daily doses of 5 60 mg showed similar effi cacy to enoxaparin. Dose response for bleeding: total daily doses of 5 20 mg showed similar safety to enoxaparin RECORD1 III THR 10 mg od Enoxaparin Composite of DVT, PE and all cause mortality Major bleeding Primary endpoint: 1.1% vs 3.7%, p 0.001 Major bleeding: 0.3% vs 0.1% RECORD2 III THR 10 mg od Enoxaparin Composite of DVT, PE and all cause mortality Major bleeding Primary endpoint: 2.0% vs 9.3%, p 0.001 Major bleeding: 0.1% vs 0.1% RECORD3 III TKR 10 mg od Enoxaparin Composite of DVT, PE, and all cause mortality Major bleeding Primary endpoint: 9.6% vs 18.9%, p 0.001 Major bleeding: 0.
6% vs 0.5% RECORD4 III TKR 10 mg od Enoxaparin Composite of DVT, PE, and all cause mortality Major bleeding Study completed, results not yet published Vascular Health and Risk Management 2008:4 1379 Novel oral antithrombotics Apizaban NCT 00097357 II TKR 5 20 mg od 2.5 10 mg bid Enoxaparin or warfarin Composite of DVT, PE and all cause mortality Major bleeding No signifi cant dose response for effi cacy. Signifi cant dose related increase in the incidence of total adjudicated bleeding events VTE treatment Rivaroxaban ODIXa DVT II 10 30 mg bid/ 40 mg od Enoxaparin and warfarin Improvement in thrombotic burden at day 21 without recurrent symptomatic VTE or VTE related death Major bleeding Primary endpoint: 53.0%, 59.2%, 56.9% and 43.8% vs 45.9% Major bleeding: 1.7%, 1.7%, 3.3% and 1.
7% vs 0.0% EINSTEIN DVT II 20 40 mg od Enoxaparin/ tinzaparin/UFH and warfarin Composite of recurrent DVT/PE related death, and reduced thrombotic burden Composite of clinically relevant major and nonmajor bleeding Primary endpoint: 6.1%, 5.4%, 6.6% vs 9.9% Major bleeding: 0.7%, 1.5% and 0.0% vs 1.5% Apixaban BOTICELLI DVT II 5 mg and 10 mg bid, 20 mg od LMWH or fondaparinux and warfarin Composite of recurrent VTE and reduced thrombotic burden Composite of major and nonmajor bleeding Primary endpoint: 6.0%, 5.6% and 2.6% vs 4.2% Major bleeding: 0.8%, 0.0%, 0.8% vs 0.0% a30 mg bid or 40 mg od based on US or European requirements. Abbreviations: THR, total hip replacement, TKR, total knee replacement, bid, twice daily, od, once daily, DVT, deep vein thrombosis, PE, pulmonary embolism. 1380 Vascular Health and Risk Management 2008:4 Lassen and Laux These trials were designed to allow pooling of the results and had the same independent blinded adjudication committees. Subjects were randomized to receive various doses of oral rivaroxaban or subcutaneous enoxaparin for 5 9 days after surgery. The