Apixaban is equally effective as conventional treatment for treatment of acute VTE
02/07/2013
A fixed-dose regimen of oral apixaban reduced the frequency of acute venous thromboembolism as effective as conventional treatment, but with fewer major bleedings.
Oral Apixaban for the Treatment of Acute Venous Thromboembolism.Literature - Agnelli G, Buller HR, Cohen A, et al.; the AMPLIFY Investigators - N Engl J Med. 2013 Jul 1
Agnelli G, Buller HR, Cohen A, et al.; the AMPLIFY Investigators
N Engl J Med. 2013 Jul 1. [Epub ahead of print]
Background
Conventional 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 [1]. 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 [4]. 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.
Main results
- 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).
Conclusion
A 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.References
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.