AMPLIFY-EXT

Apixaban after the initial Management of PuLmonary embolIsm and deep vein thrombosis with First-line therapY-EXTended treatment (2013)

Condition

Long-term VTE-prophylaxis after treatment of acute DVT and PE

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Objective

To evaluate the safety and efficacy of 2 different apixaban doses versus placebo during extended treatment following initial treatment of DVT or PE for 6–12 months

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Trial design

Randomized, double-blind phase III study
Active treatment: apixaban 5 mg (n=840) or 2.5 mg (n=813) p.o. twice daily for up to 12 months
Control treatment: placebo twice daily for up to 12 months (n=829)

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Endpoints

Primary outcome measure: composite of VTE recurrence (fatal and nonfatal PE and DVT) or death from any cause
Primary safety endpoint: major bleeding
Secondary outcome measure: bleeding during study treatment

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Trial participants

2486 patients with acute DVT or PE ≥18 years of age, who had completed 6–12 months of prior anticoagulant treatment (standard anticoagulant therapy or treatment with apixaban or enoxaparin and warfarin as participants in the AMPLIFY trial) with no symptomatic recurrence. 2482 patients were included in the intention-to-treat analyses

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Results

Efficacy outcome: Symptomatic recurrent VTE or death from VTE occurred in 14 of the 840 patients (1.7%) treated with 2.5 mg of apixaban and in 14 of the 813 patients (1.7%) given 5 mg of apixaban as compared with 73 of the 829 patients (8.8%) who were receiving placebo. 52 patients were lost to follow-up (13 in the 2.5-mg apixaban group, 20 in the 5-mg apixaban group, and 19 in the placebo group). They were classified as having had a primary outcome event. Therefore 3.8% (32 of 840 patients) with 2.5 mg of apixaban, 4.2% (34 of 814) with 5 mg of apixaban and 11.6% (32 of 840) with placebo reached the primary efficacy endpoint. The rate of death from any cause was 1.7% in the placebo group, as compared with 0.8% in the 2.5-mg apixaban group and 0.5% in the 5-mg apixaban group
Safety outcome: Major bleeding was observed in 0.2% in the 2.5-mg apixaban group, in 0.1% in the 5-mg apixaban group, and in 0.5% in the placebo group.  The rates of clinically relevant non-major bleeding were, 3.0% with 2.5 mg of apixaban, 4.2% with 5 mg of apixaban, and 2.3% with placebo

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Summary

Efficacy: Extended anticoagulation with apixaban at either a treatment dose (5 mg) or a thromboprophylactic dose (2.5 mg) resulted in a large and significant reduction in the risk of recurrent fatal or non-fatal VTE
Safety: Both of the regimen of apixaban were safe. The rates of major bleeding in the apixaban groups were low and similar to those in the placebo group

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Reference

Agnelli G, Buller HR, Cohen A, Curto M, Gallus AS, Johnson M, Porcari A, Raskob GE, Weitz JI for the AMPLIFY-EXT Investigators. Apixaban for extended treatment of venous thromboembolism. N Engl J Med 2013;368:699-708

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Corresponding author

Giancarlo Agnelli, MD, Department of Internal and Cardiovascular Medicine – Stroke Unit, University of Perugia, Piazzale Menghini 1, 06100 Perugia, Italy, agnellig@unipg.it

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