PREVENTION OF STROKE AND SYSTEMIC EMBOLIC EVENTS WITH LIXIANA®

Proven efficacy in ENGAGE AF-TIMI 48

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 efficacy endpoint was time to first stroke (ischaemic or haemorrhagic) or systemic embolic event.1

Proven efficacy in preventing stroke/SEE (systemic embolic event) - comparable to well-controlled warfarin1

Secondary and other endpoints1

  • Patients on the 30 mg reduced dose achieved efficacy consistent with overall trial results.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 as if defined by the International Society on Thrombosis and Haemostasis.

  • 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. 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.

  • *

    This non inferiority analysis included data from patients who underwent radomisation and received at least one dose of study drug during the treatment period (modified intention-to-treat population).

    The treatment period was defined as the period between administration of the first dose of study drug and either 3 days after receipt or the last dose of the end of double-blind therapy (whichever came first), with interval censoring of events during study-drug interruptions that lasted more than 3 days)

  • **

    If the LIXIANA® dosing regimen met the respecified criteria for non inferiority, that dose was compared with warfarin in a test of superiority with data from ITT population during overall study period (from randomisation to end of treatment period)

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.