AMPLIFY

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

Condition

Treatment of acute DVT and PE

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Objective

To evaluate the safety and efficacy of apixaban in preventing VTE recurrence or death in patients with DVT or PE (with and without DVT) versus the standard treatment (enoxaparin followed by warfarin)

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Trial design

Randomized, double-blind phase III study
Active treatment: apixaban 10 mg p.o. twice daily for one week and 5 mg p.o. twice daily for 6 months thereafter; placebo injections as in control treatment (n=2691)
Control treatment: enoxaparin 1 mg/kg s.c. twice daily, for at least 5 days, until INR ≥2.0; then warfarin once daily (INR 2.0–3.0) for 6 months; placebo tablets as in active treatment (n=2704)

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Endpoints

Primary efficacy endpoint: incidence of the composite of recurrent symptomatic VTE or death related to VTE
Secondary efficacy endpoints: The predefined secondary efficacy outcomes included each component of the primary efficacy outcome, as well as death from cardiovascular causes and death from any cause. An additional predefined secondary outcome was the composite of symptomatic recurrent VTE with death from cardiovascular causes, with death from any cause, or with death related to VTE plus major bleeding
Primary safety endpoint: major bleeding
Secondary safety endpoint: composite of major bleeding and clinically relevant non-major bleeding

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Trial participants

5395 patients ≥18 years of age with objectively confirmed, symptomatic proximal deep-vein thrombosis or pulmonary embolism (with or without deep-vein thrombosis). 5244 patients were included in the efficacy analysis and 5365 patients were included in the safety analysis

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Results

Efficacy outcome: The primary efficacy endpoint of recurrent VTE or death related to 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 (p<0.001 for non-inferiority; relative risk reduction 16%). The efficacy of apixaban in the patients with pulmonary embolism was similar to that in the patients with deep-vein thrombosis (primary efficacy outcome in 2.3% vs. 2.6% with conventional therapy and in 2.2% vs. 2.7% with conventional therapy, respectively)
Safety outcome: Major bleeding was observed in 0.6% (15 of 2676) of patients who received apixaban and in 1.8% (49 of 2689) of those who received conventional therapy (p<0.001 for superiority; relative risk reduction 69%). The composite outcome of major bleeding and clinically relevant non-major bleeding occurred in 4.3% of the patients in the apixaban group, as compared with 9.7% of those in the conventional-therapy group (p<0.001; relative risk reduction 56%). Rates of other adverse events were similar in the two groups

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Summary

Efficacy: For the treatment of acute VTE, a fixed-dose regimen of apixaban alone was non-inferior to conventional treatment consisting of enoxaparin followed by warfarin
Safety: Treatment with apixaban was associated with significantly less major and clinically relevant non-major bleeding

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Reference

Agnelli G, Buller HR, Cohen A, Curto M, Gallus AS, Johnson M, Masiukiewicz U, Pak R, Thompson J, Raskob GE, Weitz JI; AMPLIFY Investigators. Oral apixaban for the treatment of acute venous thromboembolism. N Engl J Med 2013;369:799-808

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Corresponding author

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

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