title: Efficacy and safety of apixaban compared with warfarin according to age for stroke prevention in atrial fibrillation: observations from the ARISTOTLE trial.
abstract: OBJECTIVE
  The risk of stroke in patients with atrial fibrillation (AF) increases with age. In the ARISTOTLE trial, apixaban when compared with warfarin reduced the rate of stroke, death, and bleeding. We evaluated these outcomes in relation to patient age.
  
  
  RESULTS
  A total of 18 201 patients with AF and a raised risk of stroke were randomized to warfarin or apixaban 5 mg b.d. with dose reduction to 2.5 mg b.d. or placebo in 831 patients with ≥2 of the following criteria: age ≥80 years, body weight ≤60 kg, or creatinine ≥133 μmol/L. We used Cox models to compare outcomes in relation to patient age during 1.8 years median follow-up. Of the trial population, 30% were <65 years, 39% were 65 to <75, and 31% were ≥75 years. The rates of stroke, all-cause death, and major bleeding were higher in the older age groups (P < 0.001 for all). Apixaban was more effective than warfarin in preventing stroke and reducing mortality across all age groups, and associated with less major bleeding, less total bleeding, and less intracranial haemorrhage regardless of age (P interaction >0.11 for all). Results were also consistent for the 13% of patients ≥80 years. No significant interaction with apixaban dose was found with respect to treatment effect on major outcomes.
  
  
  CONCLUSIONS
  The benefits of apixaban vs. warfarin were consistent in patients with AF regardless of age. Owing to the higher risk at older age, the absolute benefits of apixaban were greater in the elderly.
authors.affiliation: Department of Cardiology B, Oslo University Hospital, Oslo 0407, Norway sigrun.h@online.no.
authors.forename: Sigrun
authors.initials: S
authors.lastname: Halvorsen
authors.affiliation: Department of Cardiology B, Oslo University Hospital, Oslo 0407, Norway Institute of Clinical Medicine, University of Oslo, Norway.
authors.forename: Dan
authors.initials: D
authors.lastname: Atar
authors.affiliation: Duke Clinical Research Institute, Duke University Medical Center, Durham, NC, USA.
authors.forename: Hongqiu
authors.initials: H
authors.lastname: Yang
authors.affiliation: G. D'Annunzio Università - Chieti and Fondazione Toscana G. Monasterio, Pisa, Italy.
authors.forename: Raffaele
authors.initials: R
authors.lastname: De Caterina
authors.affiliation: Faculty of Medicine, Ankara University, Ankara, Turkey.
authors.forename: Cetin
authors.initials: C
authors.lastname: Erol
authors.affiliation: Division of Hematology, University of Washington, Seattle, WA, USA.
authors.forename: David
authors.initials: D
authors.lastname: Garcia
authors.affiliation: Duke Clinical Research Institute, Duke University Medical Center, Durham, NC, USA.
authors.forename: Christopher B
authors.initials: CB
authors.lastname: Granger
authors.affiliation: Bristol-Myers Squibb, Princeton, NJ, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Hanna
authors.affiliation: Department of Medical Sciences, Cardiology, and Uppsala Clinical Research Center, Uppsala University, Uppsala, Sweden.
authors.forename: Claes
authors.initials: C
authors.lastname: Held
authors.affiliation: Medical Department, Hospital Unit West, Herning/Holstbro, Denmark.
authors.forename: Steen
authors.initials: S
authors.lastname: Husted
authors.affiliation: Boston University Medical Center, Boston, MA, USA.
authors.forename: Elaine M
authors.initials: EM
authors.lastname: Hylek
authors.affiliation: Cardiovascular Centre, University Hospital Motol, Prague, Czech Republic.
authors.forename: Petr
authors.initials: P
authors.lastname: Jansky
authors.affiliation: Duke Clinical Research Institute, Duke University Medical Center, Durham, NC, USA.
authors.forename: Renato D
authors.initials: RD
authors.lastname: Lopes
authors.affiliation: National Institute of Cardiology, Warsaw, Poland.
authors.forename: Witold
authors.initials: W
authors.lastname: Ruzyllo
authors.affiliation: Duke Clinical Research Institute, Duke University Medical Center, Durham, NC, USA.
authors.forename: Laine
authors.initials: L
authors.lastname: Thomas
authors.affiliation: Department of Medical Sciences, Cardiology, and Uppsala Clinical Research Center, Uppsala University, Uppsala, Sweden.
authors.forename: Lars
authors.initials: L
authors.lastname: Wallentin
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D000925:Anticoagulants / Q000008:administration & dosage* / Q000009:adverse effects; D001281:Atrial Fibrillation / Q000188:drug therapy* / Q000401:mortality; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004617:Embolism / Q000401:mortality / Q000517:prevention & control; D065427:Factor Xa Inhibitors / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D006470:Hemorrhage / Q000139:chemically induced / Q000401:mortality; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D011720:Pyrazoles / Q000008:administration & dosage* / Q000009:adverse effects; D011728:Pyridones / Q000008:administration & dosage* / Q000009:adverse effects; D012307:Risk Factors; D020521:Stroke / Q000401:mortality / Q000517:prevention & control*; D016896:Treatment Outcome; D014859:Warfarin / Q000008:administration & dosage*; D055815:Young Adult
chemical_list: D000925:Anticoagulants; D065427:Factor Xa Inhibitors; D011720:Pyrazoles; D011728:Pyridones; C522181:apixaban; D014859:Warfarin
keywords: Age; Anticoagulants; Apixaban; Atrial fibrillation; Bleeding; Stroke