Apixaban versus enoxaparin for thromboprophylaxis after hip or knee replacement. Pooled analysis of major venous thromboembolism and bleeding in 8,464 patients from the ADVANCE -2 and ADVANCE-3 trials

University of Oklahoma Health Sciences Center, College of Public Health, 801 NE 13th Street, Oklahoma City, Oklahoma 73104, USA.
The Bone & Joint Journal (Impact Factor: 3.31). 02/2012; 94(2):257-64. DOI: 10.1302/0301-620X.94B2.27850
Source: PubMed


In order to compare the effect of oral apixaban (a factor Xa inhibitor) with subcutaneous enoxaparin on major venous thromboembolism and major and non-major clinically relevant bleeding after total knee and hip replacement, we conducted a pooled analysis of two previously reported double-blind randomised studies involving 8464 patients. One group received apixaban 2.5 mg twice daily (plus placebo injection) starting 12 to 24 hours after operation, and the other received enoxaparin subcutaneously once daily (and placebo tablets) starting 12 hours (± 3) pre-operatively. Each regimen was continued for 12 days (± 2) after knee and 35 days (± 3) after hip arthroplasty. All outcomes were centrally adjudicated. Major venous thromboembolism occurred in 23 of 3394 (0.7%) evaluable apixaban patients and in 51 of 3394 (1.5%) evaluable enoxaparin patients (risk difference, apixaban minus enoxaparin, -0.8% (95% confidence interval (CI) -1.2 to -0.3); two-sided p = 0.001 for superiority). Major bleeding occurred in 31 of 4174 (0.7%) apixaban patients and 32 of 4167 (0.8%) enoxaparin patients (risk difference -0.02% (95% CI -0.4 to 0.4)). Combined major and clinically relevant non-major bleeding occurred in 182 (4.4%) apixaban patients and 206 (4.9%) enoxaparin patients (risk difference -0.6% (95% CI -1.5 to 0.3)). Apixaban 2.5 mg twice daily is more effective than enoxaparin 40 mg once daily without increased bleeding.

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    • "Apixaban is an oral factor Xa inhibitor with a rapid onset of action that is administered in fixed doses without the need for laboratory monitoring. Apixaban is effective for the prevention of VTE after major orthopedic surgery14. The AMPLIFY Extension study was a double-blind trial in which 2,486 patients with VTE were randomized to receive two different doses of apixaban (2.5 mg or 5 mg twice daily) or placebo after 6-12 months of anticoagulation treatment. "
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