Apixaban Is as Effective for Treatment of Acute Venous Thromboembolism as Conventional Therapy and Reduces Bleeding Risk

EBM Focus - Volume 8, Issue 29

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Reference: N Engl J Med 2013 Jul 1 early online, (level 1 [likely reliable] evidence)

The standard treatment for venous thromboembolism (VTE) includes short-term treatment with a parenteral heparin-type anticoagulant (e.g. enoxaparin) and long-term treatment with warfarin, which requires frequent monitoring and dose adjustment. Newer anticoagulants, like fixed-dose oral factor Xa inhibitors, could simplify VTE management by reducing the need for injections and monitoring. The AMPLIFY trial compared the efficacy of the factor Xa inhibitor apixaban to conventional therapy for treatment of acute VTE in 5,395 adult patients.

Patients (mean age 57 years) with acute symptomatic proximal deep vein thrombosis or pulmonary embolism were randomized to 1 of 2 interventions and followed for 7 months. The conventional therapy group received enoxaparin 1 mg/kg subcutaneously every 12 hours for ≥ 5 days plus warfarin with target international normalized ratio (INR) 2-3 for 6 months. The apixaban group received apixaban 10 mg orally twice daily for the first 7 days, then 5 mg twice daily for 6 months. Blinding was maintained through placebo subcutaneous injections and placebo warfarin with sham INR monitoring. The primary outcome was a composite of recurrent symptomatic VTE and VTE-related death.

Primary outcome events occurred in 2.3% with apixaban vs. 2.7% with conventional therapy group (not significant). The apixaban group had lower rates of major bleeding (0.6% vs. 1.8%, p < 0.001, NNT 84) and clinically-relevant nonmajor bleeding (3.8% vs. 8%, p < 0.05, NNT 24). There were no significant differences in all-cause mortality (1.5% vs. 1.9%) or in serious adverse events. These data in patients with acute VTE add to recently published evidence regarding the efficacy and safety of long-term apixaban use for prevention of recurrent VTE (DynaMed EBM Focus Volume 8, Issue 11). Apixaban is currently FDA-approved only for use in patients with nonvalvular atrial fibrillation.

For more information, see the Anticoaqulant therapy for venous thromboembolism topic in DynaMed.