SUPERIOR REDUCTION IN CLINICALLY RELEVANT BLEEDING

Once-daily LIXIANA® (edoxaban) was superior to warfarin in reducing the risk of clinically relevant bleeding across a broad range of eligible VTE patients.1 (Clinically relevant bleeding was defined as the composite of major* and clinically relevant nonmajor [CRNM] § bleeding).

The primary safety endpoint in Hokusai-VTE was the incidence of adjudicated clinically relevant bleeding.

  • Superior 19% relative risk reduction in clinically relevant bleeding (the composite of major* and CRNM§ bleeding) compared with well-managed warfarin (HR, 0.81; 95% CI, 0.71 to 0.94; P=0.004 for superiority)1


In major subpopulations of eligible patients, safety results were consistent with the overall study population.1,2

Once-daily LIXIANA® (edoxaban) was associated with low rates of the following types of bleeding1:

  • A phase 3, multinational, double-blind, double-dummy, event-driven, noninferiority trial designed to evaluate the efficacy and safety of once-daily LIXIANA® (edoxaban) 60 mg vs dose-adjusted warfarin (target INR of 2.0-3.0) in patients with VTE (n=8292) after initial treatment with heparin. LIXIANA® (edoxaban) dosage was reduced by half if any of the following was present at randomisation or during the course of the study: creatinine clearance 30-50 mL/min, body weight ≤60 kg, or use of concomitant potent P-gp inhibitors. Patients received the study drug for 3 to 12 months. The primary efficacy outcome was recurrent symptomatic VTE. The principal safety outcome was clinically relevant bleeding (defined as major* or clinically relevant nonmajor bleeding§). Warfarin therapy was proactively monitored throughout the trial, resulting in a median TTR of 63.5%. Patients 18 years of age or older were eligible if they had objectively diagnosed, acute, symptomatic DVT involving the popliteal, femoral, or iliac veins or acute symptomatic PE (with or without DVT).1

  • *

    Major bleeding in nonsurgical patients was defined as5

    1. Fatal bleeding, and/or
    2. Symptomatic bleeding in critical area or organ, such as intracranial, intraspinal, intraocular, retroperitoneal, intra-articular, pericardial, or intramuscular with compartment syndrome, and/or
    3. Bleeding causing a fall in haemoglobin level of 20 g/L-1 (1.24 mml/L-1) or more, or leading to transfusing of 2 or more units of whole blood or red cells.
  • §

    Clinically relevant nonmajor bleeding was defined as overt bleeding not meeting the criteria for major bleeding* but associated with medical intervention, unscheduled contact (visit or telephone call) with a physician, (temporary) cessation of study treatment, or associated with any other discomfort such as pain, or impairment of activities of daily life.1

  • One or more of the following factors: moderate renal impairment (creatinine clearance of 30-50 mL/min), low body weight (≤60 kg/132 lbs), concomitant use of P-glycoprotein inhibitors (eg, cyclosporine, dronedarone, ketoconazole, erythromycin).4