• Thrombophilia
• Hematology Clinical Trials
• Thrombotic Disorders

• Thrombophilia
• Hematology Clinical Trials
• Thrombotic Disorders
• Hematology

Apixaban, an oral factor Xa inhibitor, is noninferior to enoxaparin plus warfarin for the treatment of acute symptomatic proximal deep vein thrombosis (DVT) and pulmonary embolism (PE), and is associated with significantly less bleeding compared with conventional therapy. Administered in fixed doses, apixaban may simplify the treatment of acute venous thromboembolism (VTE). Giancarlo Agnelli, MD, University of Perugia, Perugia, Italy, presented the results of the Efficacy and Safety Study of Apixaban for the Treatment of Deep Vein Thrombosis or Pulmonary Embolism [AMPLIFY; NCT00643201].

The purpose of this 6–month, randomized, double-blind, noninferiority trial was to compare the efficacy and safety of apixaban (10 mg BID for 7 days, followed by 5 mg BID) with conventional anticoagulant therapy consisting of subcutaneous enoxaparin (1 mg/kg BID) followed by warfarin (target INR 2 to 3). The study enrolled adults with acute symptomatic proximal DVT or PE. The criteria for noninferiority required that the upper limit of the 95% CIs be below prespecified margins for both the relative risk (<1.8) and the absolute risk difference (<3.5%). The diagnosis at study entry, the extent of initial DVT or PE, and all suspected outcomes were adjudicated by an independent committee, whose members were unaware of study group assignments.

The primary efficacy outcome was symptomatic recurrent VTE or VTE-related death. Other outcomes included recurrent symptomatic VTE or cardiovascular-related death, and recurrent symptomatic VTE or all-cause death. The primary safety outcome was adjudicated major bleeding. The secondary safety outcome was the composite of major bleeding and clinically relevant nonmajor bleeding.

Patients (n=5400; mean age, 57 years; 58% men) were enrolled at 358 centers in 28 countries and assigned to receive either apixaban (n=2691) or conventional therapy (n=2704). Approximately 65% of patients entered the study with DVT, 25% with PE, and −9% with DVT plus PE. VTE was unprovoked in 90% of patients. Most (75%) patients had a femoral or more proximal DVT, while 38% had extensive PE that included ≥2 lobes with ≥50% of the vasculature for each lobe affected.

After 6 months, 57 (2.3%) of the patients receiving apixaban experienced a first recurrent VTE or VTE-related death compared with 71 (2.7%) receiving conventional therapy. Apixaban was noninferior to conventional treatment (relative risk [RR], 0.84; 95% CI, 0.60 to 1.18; p<0.0001 for noninferiority; Table 1). Similar results were seen with the secondary outcomes.

Days to first recurrent VTE or VTE-related death, the majority of which occurred in the first 30 days, were similar in the two treatment groups. The percentage of time in therapeutic range was 60.9% for warfarin-treated patients.

In the apixaban group, 15 (0.6%) patients had major bleeding versus 49 (1.8%) in the conventionally treated group (RR, 0.31; 95% CI, 0.17 to 0.55; p<0.0001 superiority for apixaban). Clinically relevant nonmajor bleeding and major or clinically relevant nonmajor bleeding occurred in 3.9% and 4.3% of patients in the apixaban group and 8.0% and 9.7% of patients in the conventional group, respectively.

Apixaban administered in a simple, fixed-dose regimen, may be an option for the extended treatment of VTE. It is noninferior to conventional therapy for preventing recurrent VTE, with similar efficacy in patients with DVT and PE, and clinically important and statistically significant reduction in major bleeding of 69%.

This study was simultaneously published [Agnelli G et al. N Engl J Med 2013].

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