title: Efficacy and Safety of Edoxaban in Elderly Patients With Atrial Fibrillation in the ENGAGE AF-TIMI 48 Trial.
abstract: Elderly patients with atrial fibrillation are at higher risk of both ischemic and bleeding events compared to younger patients. In a prespecified analysis from the ENGAGE AF-TIMI 48 trial, we evaluate clinical outcomes with edoxaban versus warfarin according to age.
  
  
  
  Twenty-one thousand one-hundred and five patients enrolled in the ENGAGE AF-TIMI 48 trial were stratified into 3 prespecified age groups: <65 (n=5497), 65 to 74 (n=7134), and ≥75 (n=8474) years. Older patients were more likely to be female, with lower body weight and reduced creatinine clearance, leading to higher rates of edoxaban dose reduction (10%, 18%, and 41% for the 3 age groups, P<0.001). Stroke or systemic embolic event (1.1%, 1.8%, and 2.3%) and major bleeding (1.8%, 3.3%, and 4.8%) rates with warfarin increased across age groups (Ptrend<0.001 for both). There were no interactions between age group and randomized treatment in the primary efficacy and safety outcomes. In the elderly (≥75 years), the rates of stroke/systemic embolic event were similar with edoxaban versus warfarin (hazard ratio 0.83 [0.66-1.04]), while major bleeding was significantly reduced with edoxaban (hazard ratio 0.83 [0.70-0.99]). The absolute risk difference in major bleeding (-82 events/10 000 pt-yrs) and in intracranial hemorrhage (-73 events/10 000 pt-yrs) both favored edoxaban over warfarin in older patients.
  
  
  
  Age has a greater influence on major bleeding than thromboembolic risk in patients with atrial fibrillation. Given the higher rates of bleeding and death with increasing age, treatment of elderly patients with edoxaban provides an even greater absolute reduction in safety events over warfarin, compared to treatment with edoxaban versus warfarin in younger patients.
  
  
  
  URL: https://www.clinicaltrials.gov/. Unique identifier: NCT00781391.
authors.affiliation: TIMI Study Group, Cardiovascular Division, Brigham and Women's Hospital and Harvard Medical School, Boston, MA Tokai University Hospital, Isehara, Japan.
authors.forename: Eri Toda
authors.initials: ET
authors.lastname: Kato
authors.affiliation: TIMI Study Group, Cardiovascular Division, Brigham and Women's Hospital and Harvard Medical School, Boston, MA rgiugliano@partners.org.
authors.forename: Robert P
authors.initials: RP
authors.lastname: Giugliano
authors.affiliation: TIMI Study Group, Cardiovascular Division, Brigham and Women's Hospital and Harvard Medical School, Boston, MA.
authors.forename: Christian T
authors.initials: CT
authors.lastname: Ruff
authors.affiliation: Osaka National Hospital, Osaka, Japan.
authors.forename: Yukihiro
authors.initials: Y
authors.lastname: Koretsune
authors.affiliation: The Cardiovascular Institute, Tokyo, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Yamashita
authors.affiliation: Military Hospital, Budapest, Hungary.
authors.forename: Robert Gabor
authors.initials: RG
authors.lastname: Kiss
authors.affiliation: TIMI Study Group, Cardiovascular Division, Brigham and Women's Hospital and Harvard Medical School, Boston, MA.
authors.forename: Francesco
authors.initials: F
authors.lastname: Nordio
authors.affiliation: TIMI Study Group, Cardiovascular Division, Brigham and Women's Hospital and Harvard Medical School, Boston, MA.
authors.forename: Sabina A
authors.initials: SA
authors.lastname: Murphy
authors.affiliation: Daiichi Sankyo, Tokyo, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Kimura
authors.affiliation: Daiichi Sankyo, Parsippany, NJ.
authors.forename: James
authors.initials: J
authors.lastname: Jin
authors.affiliation: Daiichi Sankyo, Parsippany, NJ.
authors.forename: Hans
authors.initials: H
authors.lastname: Lanz
authors.affiliation: Daiichi Sankyo, Parsippany, NJ.
authors.forename: Michele
authors.initials: M
authors.lastname: Mercuri
authors.affiliation: TIMI Study Group, Cardiovascular Division, Brigham and Women's Hospital and Harvard Medical School, Boston, MA.
authors.forename: Eugene
authors.initials: E
authors.lastname: Braunwald
authors.affiliation: TIMI Study Group, Cardiovascular Division, Brigham and Women's Hospital and Harvard Medical School, Boston, MA.
authors.forename: Elliott M
authors.initials: EM
authors.lastname: Antman
mesh_terms: D000367:Age Factors; D000368:Aged; D000925:Anticoagulants / Q000627:therapeutic use; D001281:Atrial Fibrillation / Q000150:complications / Q000188:drug therapy*; D004311:Double-Blind Method; D004617:Embolism / Q000209:etiology / Q000517:prevention & control*; D065427:Factor Xa Inhibitors / Q000627:therapeutic use*; D005260:Female; D006470:Hemorrhage / Q000139:chemically induced* / Q000453:epidemiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D011725:Pyridines / Q000627:therapeutic use*; D020521:Stroke / Q000209:etiology / Q000517:prevention & control*; D013844:Thiazoles / Q000627:therapeutic use*; D016896:Treatment Outcome; D014859:Warfarin / Q000627:therapeutic use
chemical_list: D000925:Anticoagulants; D065427:Factor Xa Inhibitors; D011725:Pyridines; D013844:Thiazoles; D014859:Warfarin; C552171:edoxaban
keywords: antithrombotic; bleeding; death; elderly; stroke