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The AMPLIFY-EXT trial is an extension of the AMPLIFY trial which originally investigated the use of apixaban for the initial treatment of acute venous thromboembolism (VTE) including deep vein thrombosis (DVT) and/or pulmonary embolism (PE). The AMPLIFY trial compared apixaban with the combination of enoxaparin and warfarin (conventional therapy) for VTE. Patients were randomized to full-dose apixaban (10 mg twice daily for 7 days followed by 5 mg twice daily) or enoxaparin followed by warfarin. The results showed that apixaban is non-inferior to enoxaparin followed by warfarin in preventing recurrent VTE while having a significantly lower bleeding risk.
The AMPLIFY-EXT is an extension of the original trial, which investigated whether continuing apixaban in half-dose 2.5 mg BID and 5 mg BID is beneficial for preventing recurrent VTE. The trial showed that both doses of apixaban significantly reduced the risk of recurrent VTE and all-cause mortality when compared to placebo. There was no significant increase in major bleeding either. Therefore, the AMPLIFY-EXT trial has supported the use of low-dose apixaban 2.5 mg BID for the prophylaxis of VTE after an initial treatment of VTE has been completed.
Consider reducing the dose of apixaban from 5 mg BID after completing an initial course of full dose anticoagulation (usually 3-6 months) to 2.5 mg BID when extended or indefinite therapy is required. However, dose reduction should be carefully considered in high-risk patients such as those with recurrent VTE, severe thrombophilia or antiphospholipidic syndrome, active cancer-associated VTE, or other persistent risk factors.
Abstract
Background
Apixaban, an oral factor Xa inhibitor that can be administered in a simple, fixed-dose regimen, may be an option for the extended treatment of venous thromboembolism.
Methods
In this randomized, double-blind study, we compared two doses of apixaban (2.5 mg and 5 mg, twice daily) with placebo in patients with venous thromboembolism who had completed 6 to 12 months of anticoagulation therapy and for whom there was clinical equipoise regarding the continuation or cessation of anticoagulation therapy. The study drugs were administered for 12 months.
Results
A total of 2486 patients underwent randomization, of whom 2482 were included in the intention-to-treat analyses. Symptomatic recurrent venous thromboembolism or death from venous thromboembolism occurred in 73 of the 829 patients (8.8%) who were receiving placebo, as compared with 14 of the 840 patients (1.7%) who were receiving 2.5 mg of apixaban (a difference of 7.2 percentage points; 95% confidence interval [CI], 5.0 to 9.3) and 14 of the 813 patients (1.7%) who were receiving 5 mg of apixaban (a difference of 7.0 percentage points; 95% CI, 4.9 to 9.1) (P<0.001 for both comparisons). The rates of major bleeding were 0.5% in the placebo group, 0.2% in the 2.5-mg apixaban group, and 0.1% in the 5-mg apixaban group. The rates of clinically relevant nonmajor bleeding were 2.3% in the placebo group, 3.0% in the 2.5-mg apixaban group, and 4.2% in the 5-mg apixaban group. 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.
Conclusions
Extended anticoagulation with apixaban at either a treatment dose (5 mg) or a thromboprophylactic dose (2.5 mg) reduced the risk of recurrent venous thromboembolism without increasing the rate of major bleeding. (Funded by Bristol-Myers Squibb and Pfizer; AMPLIFY-EXT ClinicalTrials.gov number, NCT00633893.)
