Apixaban is equally effective as conventional treatment for treatment of acute VTELiterature - Agnelli G, Buller HR, Cohen A, et al.; the AMPLIFY Investigators - N Engl J Med. 2013 Jul 1
Oral Apixaban for the Treatment of Acute Venous Thromboembolism.
Agnelli G, Buller HR, Cohen A, et al.; the AMPLIFY Investigators
N Engl J Med. 2013 Jul 1. [Epub ahead of print]
BackgroundConventional treatment of venous thromboembolism (VTE) consists of a parenteral anticoagualant (e.g. enoxaparin) for at least 5 days, and warfarin started at this time and continued for at least 3 months . This regimen is effective but it requires daily subcutaneous injections of enoxaparin and warfarin therapy requires coagulation monitoring and dose adjustment.
Apixaban is an oral factor Xa inhibitor with a rapid onset of action. Its predictable pharmacokinetics allow a fixed-dose regimen. Apixaban may therefore simplify the treatment of VTE because the initial parenteral anticoagulant therapy and the laboratory monitoring is no longer needed [2.3]. Apixaban has been shown to be effective for the prevention of recurrent VTE in patients who have completed 6-12 months of anticoagulant therapy for acute VTE. Rates of bleeding were similar to those for placebo . The Apixaban for the Initial Management of Pulmonary Embolism and Deep-Vein Thrombosis as First-Line Therapy (AMPLIFY) trial compares apixaban (10 mg twice daily for the first 7 days, followed by 5 mg twice daily for 6 months) with conventional anticoagulant therapy (enoxaparin 1 mg/kg bodyweight every 12 hours for at least 5 days and warfarin started concomitantly and continued for 6 months) in patients with acute symptomatic venous thromboembolism. In this randomised, double-blind trial, 5400 patients with deep-vein thrombosis, pulmonary embolism or both were followed for 6 months. The primary efficacy outcome was incidence of adjudicated composite of recurrent symptomatic VTE or death related to VTE.
- The primary efficacy outcome of recurrent VTE occurred in 59 of 2609 patients (2.3%) in the apixaban group and in 71 of 2635 (2.7%) in the conventional therapy group (risk difference: -0.4, 95%CI: -1.3 to 0.4, P<0.001), yielding a relative risk of 0.84 (95%CI: 0.60-1.18, P<0.001 for non-inferiority).
- In a subgroup of patients who had deep-vein thrombosis at enrollment, the primary efficacy outcome occurred in 38 of 1698 patients (2.2%) receiving apixaban and in 47 of 1736 (2.7%) of patients receiving conventional treatment (relative risk: 0.83, 95%CI: 0.54-1.26).
- Major bleeding occurred in 15 of 2676 patients (0.6%) in the apixaban group and in 49 of 2689 (1.8%) in the conventional therapy group, yielding a relative risk of 0.31 (95%CI: -1.7 to -0.6).
ConclusionA fixed-dose regimen of oral apixaban alone was as effective as conventional treatment (enoxaparin and warfarin) for the treatment of acute VTE, and was associated with a clinically relevant reduction of 69% in major bleeding.
1. Kearon C, Akl EA, Comerota AJ, et al. Antithrombotic therapy for VTE disease: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest 2012;141: Suppl:e419S-e494S. [Erratum, Chest 2012;142:1698-704.]
2. The EINSTEIN Investigators. Oral rivaroxaban for symptomatic venous thromboembolism. N Engl J Med 2010;363:2499-510.
3. The EINSTEIN–PE Investigators. Oral rivaroxaban for the treatment of symptomatic pulmonary embolism. N Engl J Med 2012;366:1287-97.
4. Agnelli G, Buller HR, Cohen A, et al. Apixaban for extended treatment of venous thromboembolism. N Engl J Med 2013;368:699-708.
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