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
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.
Available from: PubMed Central
- "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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ABSTRACT: Venous thromboembolism (VTE), which includes pulmonary embolism and deep vein thrombosis, is an important cause of morbidity and mortality. The aim of this review is to summarize the findings from clinically important publications over the last year in the area of VTE. In this review, we discuss 11 randomized controlled trials published from March 2013 to April 2014. The COAG and the EU-PACT trials indicate that pharmacogenetic testing has either no usefulness in the initial dosing of vitamin K antagonists or marginal usefulness in the Caucasian population. Recent clinical trials with novel oral anticoagulants (NOACs) have demonstrated that the efficacy and safety of rivaroxaban, apixaban, edoxaban, and dabigatran are not inferior to those of conventional anticoagulants for the treatment of VTE. The PEITHO and ULTIMA trials suggested that rescue thrombolysis or catheter-directed thrombolysis may maximize the clinical benefits and minimize the bleeding risk. Lastly, riociguat has a proven efficacy in treating chronic thromboembolic pulmonary hypertension. In the future, NOACs, riociguat, and catheter-directed thrombolysis have the potential to revolutionize the management of patients with VTE.
Tuberculosis and Respiratory Diseases 09/2014; 77(3):105-10. DOI:10.4046/trd.2014.77.3.105
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ABSTRACT: Thrombosis plays a key role in the pathophysiology of acute coronary syndromes (ACS). The management of patients with ACS includes interventional procedures and use of antithrombotic agents acutely, and dual antiplatelet therapy (aspirin and a P2Y12 receptor antagonist) for secondary prevention. However, patients with recent ACS remain at a substantial residual risk for recurrent ischemic events or death. The idea of follow-up treatment with an oral anticoagulant on top of standard therapy seems promising. Warfarin was the first oral anticoagulant thoroughly investigated in this direction, but the widespread long-term use of warfarin in ACS has been limited by challenges associated with pharmacodynamic/pharmacokinetic deficiencies of the drug and the risk of bleeding. Novel oral anticoagulants, such as direct thrombin inhibitors (DTIs) and FXa inhibitors overcome the downsides of VKAs. Ximelagatran was the first DTI, investigated and proven to be effective in prevention of recurrent ischemic events in ACS patients, but the drug association with hepatotoxicity prompted its withdrawal. Dabigatran etexilate, apixaban, darexaban (YM150) and TAK-442 were studied in phase II dose-escalation trials in order to determine the balance between clinical effectiveness and bleeding risk in daily use with dual antiplatelet therapy, with both positive and negative results. Rivaroxaban is the only agent that completed a phase III trial, showing reduction in recurrent ischemic events rate and death from cardiovascular causes as well as all-cause death. This review summarizes the data from completed and ongoing clinical trials of the new oral anticoagulants in patients with ACS.
05/2012; 7(3):195-208. DOI:10.2174/157488412800958677
Available from: Amir K Jaffer
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ABSTRACT: Patients undergoing total knee and total hip replacement (THR/TKR) surgery are at high risk of venous thromboembolism (VTE), and routine thromboprophylaxis is recommended after these procedures. However, current thromboprophylaxis may require daily injections, careful anticoagulation monitoring, and dietary restrictions, which can lead to poor patient compliance and suboptimal outcomes. Therefore, there is an unmet need for simpler medication options. Newer oral anticoagulants have improved efficacy over standard treatments, with convenient dosing regimens, more predictable pharmacologic profiles that reduce the need for anticoagulation monitoring, and fewer drug or food interactions. These drugs have the potential to simplify anticoagulation after THR or TKR surgery, which may lead to improved adherence, thus lowering the incidence of VTE and associated complications after surgery.
Journal of Thrombosis and Thrombolysis 06/2012; 34(4):518-25. DOI:10.1007/s11239-012-0751-5 · 2.17 Impact Factor
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