Apixaban compared with warfarin in patients with atrial fibrillation and previous stroke or transient ischaemic attack: a subgroup analysis of the ARISTOTLE trial

The Lancet Neurology, 05/21/2012

The effects of apixaban versus warfarin were consistent in patients with atrial fibrillation (AF) with and without previous stroke or transient ischaemic attack (TIA). Owing to the higher risk of these outcomes in patients with previous stroke or TIA, the absolute benefits of apixaban might be greater in this population.

Methods

  • Between Dec 19, 2006, and April 2, 2010, patients were enrolled in the ARISTOTLE trial at 1034 clinical sites in 39 countries.
  • 18 201 patients with AF or atrial flutter were randomly assigned to receive apixaban 5 mg twice daily or warfarin (target international normalised ratio 2•0–3•0).
  • The median duration of follow–up was 1•8 years (IQR 1•4–2•3).
  • The primary efficacy outcome was stroke or systemic embolism, analysed by intention to treat.
  • The primary safety outcome was major bleeding in the on–treatment population.
  • All participants, investigators, and sponsors were masked to treatment assignments.
  • In this subgroup analysis, authors estimated event rates and used Cox models to compare outcomes in patients with and without previous stroke or TIA.

Results

  • Of the trial population, 3436 (19%) had a previous stroke or TIA.
  • In the subgroup of patients with previous stroke or TIA, the rate of stroke or systemic embolism was 2•46 per 100 patient–years of follow–up in the apixaban group and 3•24 in the warfarin group (hazard ratio [HR] 0•76, 95% CI 0•56 to 1•03); in the subgroup of patients without previous stroke or TIA, the rate of stroke or systemic embolism was 1•01 per 100 patient–years of follow–up with apixaban and 1•23 with warfarin (HR 0•82, 95% CI 0•65 to 1•03; p for interaction=0•71).
  • The absolute reduction in the rate of stroke and systemic embolism with apixaban versus warfarin was 0•77 per 100 patient–years of follow–up (95% CI –0•08 to 1•63) in patients with and 0•22 (–0•03 to 0•47) in those without previous stroke or TIA.
  • The difference in major bleeding with apixaban compared with warfarin was 1•07 per 100 patient–years (95% CI 0•09–2•04) in patients with and 0•93 (0•54–1•32) in those without previous stroke or TIA.

Print Article Summary