SUPERIOR REDUCTION OF MAJOR BLEEDING1,*

Once-daily LIXIANA® (edoxaban) was superior to warfarin in reducing the risk of major bleeding events1,*

The primary safety endpoint in the ENGAGE AF-TIMI 48 clinical trial was reduction in risk of major bleeding* events.


The safety of LIXIANA® (edoxaban) was also established in subpopulations of eligible NVAF patients—including those with factors that increase the risk of bleeding.1,2,*

Once-daily LIXIANA® (edoxaban) was also associated with significantly lower rates of intracranial, life-threatening, and fatal bleeding compared with well-managed warfarin1

Once-daily LIXIANA® (edoxaban) significantly reduced the primary net clinical outcome compared with warfarin1

The primary net clinical outcome of stroke, systemic embolic events, major bleeding, and all-cause mortality was reduced by 11% compared with well-managed warfarin (7.26% vs 8.11%, respectively; HR, 0.89; 95% CI, 0.83 to 0.96; P=0.003)1

  • A phase 3, multinational, double-blind, double-dummy, noninferiority trial comparing once-daily LIXIANA® (edoxaban) with warfarin in 21,105 patients with nonvalvular atrial fibrillation at moderate to high risk of stroke (CHADS2 ≥2). Patients were randomised to receive warfarin (n=7036), LIXIANA® (edoxaban) 60 mg (n=7035) or LIXIANA® (edoxaban) 30 mg (n=7034) for up to 2.8 years (median follow-up duration). LIXIANA® (edoxaban) dosage was reduced by half if one or more of the following were present at randomisation or during the course of the study: creatinine clearance 30-50 mL/min, body weight ≤60 kg, or concomitant verapamil, quinidine, or dronedarone. The primary efficacy endpoint was reduction in stroke or systemic embolic events, and the primary safety endpoint was reduction in major bleeding events. Warfarin therapy (target INR of 2.0-3.0) was proactively monitored throughout the trial, resulting in a median time within therapeutic range (TTR) of 68.4%. Adverse events (excluding bleeding) and discontinuation rates were similar among the 3 treatment groups.1

  • *

    Major bleeding in nonsurgical patients was defined as3

    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.
  • §

    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