MAJOR BLEEDING DATA FOR LIXIANA®

ENGAGE AF-TIMI 48 was the largest (21,105) and longest (median follow up 2.8 years) comparative NVAF study to date with a NOAC. The primary safety endpoint was major bleeding as defined by the International Society on Thrombosis and Haemostasis.1

Superior reduction in major bleeding vs. well-controlled warfarin1

Significant reduction across all bleeding endpoints vs. well-controlled warfarin1

  • Patients on the 30mg reduced dose of LIXIANA® achieved a reduction in major bleeding consistent with overall trial results in NVAF.1,2


  • A Phase 3, three-arm randomised, double-blind, double-dummy, event-driven trial comparing two once-daily regimens of LIXIANA® with warfarin in 21,105 patients with moderate to high risk of atrial fibrillation and stroke (CHADS2 score ≥2).

  • Patients were randomised to receive warfarin (n=7,036), LIXIANA® 60 mg (n=7,035) or LIXIANA® 30 mg (n=7,034) for up to 2.8 years (median follow-up duration).

  • LIXIANA® dosage was reduced by 50% if patients had one or more of the following clinical factors: moderate renal impairment (CrCl 30-50 ml/min, low body weight (≤60 kg/132 lbs), or concomitant use of P-glycoprotein (p-gp) inhibitors.

  • The primary efficacy endpoint was time to first stroke (ischaemic or haemorrhagic) or systemic embolism, and the primary safety endpoint was major bleeding defined by the International Society on Thrombosis and Haemostasis as (i) fatal bleeding; and/or (ii) symptomatic bleeding in critical area or organ, such as intracranial, intraspinal, intraocular, retroperitoneal, intraarticular, pericardial, or intramuscular with compartment syndrome, and/or (iii) bleeding causing a fall in haemoglobin level of 2.0 g/dL or more, or leading to transfusion of two or more units of whole blood or red cells.3

  • 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%.

  • Note: The SPC differs from the clinical trial. Hence, no dose adjustment is required for concomitant use of verapamil, amiodarone and quinidine. In patients taking LIXIANA® and the following P-gp inhibitors; dronedarone, erythromycin, ketoconazole or ciclosporin, the recommended dose is LIXIANA® 30 mg once daily.

References

  1. Giugliano RP et al. NEJM 2013;369(22):2093–2104.
  2. Giugliano RP et al. NEJM 2013;369(22):2093–2104. Supplementary information table.
  3. Schulman S and Kearon C. J Thromb Haemost 2005;3(4):692–694.