title: Warfarin Initiation, Atrial Fibrillation, and Kidney Function: Comparative Effectiveness and Safety of Warfarin in Older Adults With Newly Diagnosed Atrial Fibrillation.
abstract: BACKGROUND
  The effectiveness and safety of warfarin use among patients with atrial fibrillation (AF) and reduced kidney function are uncertain.
  
  
  METHODS
  Community-based retrospective cohort study (May 1, 2003, to March 31, 2012) using province-wide laboratory and administrative data in Alberta, Canada.
  
  
  METHODS
  14,892 adults 66 years or older with new AF and a measurement of kidney function. Long-term dialysis patients or kidney transplant recipients were excluded.
  
  
  METHODS
  Propensity scores were used to construct a matched-pairs cohort of patients with AF who did and did not have a warfarin prescription within a 60-day period surrounding their AF diagnosis.
  
  
  RESULTS
  Within 1 year of initiating warfarin therapy (or the matched date for nonusers): (1) the composite of all-cause death, ischemic stroke, or transient ischemic attack (also assessed as separate end points) and (2) first hospitalization or emergency department visit for a major bleeding episode defined as an intracranial, upper or lower gastrointestinal, or other bleeding.
  
  
  METHODS
  Baseline glomerular filtration rate (GFR) was estimated using the CKD-EPI creatinine equation. Patients were matched within estimated GFR (eGFR) categories: ≥90, 60 to 89, 45 to 59, 30 to 44, and <30mL/min/1.73m2. Information for baseline characteristics (sociodemographics, comorbid conditions, and prescription drug use) was obtained.
  
  
  RESULTS
  Across eGFR categories, warfarin therapy initiation was associated with lower risk for the composite outcome compared to nonuse (adjusted HRs [95% CI] for eGFR categories ≥ 90, 60-89, 45-59, 30-44, and <30mL/min/1.73m2: 0.59 [0.35-1.01], 0.61 [0.54-0.70], 0.55 [0.47-0.65], 0.54 [0.44-0.67], and 0.64 [0.47-0.87] mL/min/1.73m2, respectively). Compared to nonuse, warfarin therapy was not associated with higher risk for major bleeding except for those with eGFRs of 60 to 89mL/min/1.73m2(HR, 1.36; 95% CI, 1.13-1.64).
  
  
  CONCLUSIONS
  Selection bias.
  
  
  CONCLUSIONS
  Among older adults with AF, warfarin therapy initiation was associated with a significantly lower 1-year risk for the composite outcome across all strata of kidney function. The risk for major bleeding associated with warfarin use was increased only among those with eGFRs of 60 to 89mL/min/1.73m2.
authors.affiliation: Cumming School of Medicine, Division of Nephrology, University of Calgary, Alberta, Canada; The George Institute for Global Health, The University of Sydney, Sydney, Australia.
authors.forename: Min
authors.initials: M
authors.lastname: Jun
authors.affiliation: Cumming School of Medicine, Division of Nephrology, University of Calgary, Alberta, Canada; Department of Community Health Sciences, University of Calgary, Calgary, Alberta, Canada.
authors.forename: Matthew T
authors.initials: MT
authors.lastname: James
authors.affiliation: Cumming School of Medicine, Division of Nephrology, University of Calgary, Alberta, Canada.
authors.forename: Zhihai
authors.initials: Z
authors.lastname: Ma
authors.affiliation: Cumming School of Medicine, Division of Nephrology, University of Calgary, Alberta, Canada.
authors.forename: Jianguo
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Cumming School of Medicine, Division of Nephrology, University of Calgary, Alberta, Canada; Department of Community Health Sciences, University of Calgary, Calgary, Alberta, Canada.
authors.forename: Marcello
authors.initials: M
authors.lastname: Tonelli
authors.affiliation: Department of Medicine, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Finlay A
authors.initials: FA
authors.lastname: McAlister
authors.affiliation: Cumming School of Medicine, Division of Nephrology, University of Calgary, Alberta, Canada; Department of Community Health Sciences, University of Calgary, Calgary, Alberta, Canada.
authors.forename: Braden J
authors.initials: BJ
authors.lastname: Manns
authors.affiliation: Cumming School of Medicine, Division of Nephrology, University of Calgary, Alberta, Canada; Department of Community Health Sciences, University of Calgary, Calgary, Alberta, Canada.
authors.forename: Pietro
authors.initials: P
authors.lastname: Ravani
authors.affiliation: Cumming School of Medicine, Division of Nephrology, University of Calgary, Alberta, Canada; Department of Community Health Sciences, University of Calgary, Calgary, Alberta, Canada.
authors.forename: Robert R
authors.initials: RR
authors.lastname: Quinn
authors.affiliation: Department of Medicine, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Natasha
authors.initials: N
authors.lastname: Wiebe
authors.affiliation: The George Institute for Global Health, The University of Sydney, Sydney, Australia.
authors.forename: Vlado
authors.initials: V
authors.lastname: Perkovic
authors.affiliation: Libin Cardiovascular Institute of Alberta, University of Calgary, Calgary, Alberta, Canada.
authors.forename: Stephen B
authors.initials: SB
authors.lastname: Wilton
authors.affiliation: Section of Nephrology, Baylor College of Medicine, Houston, TX.
authors.forename: Wolfgang C
authors.initials: WC
authors.lastname: Winkelmayer
authors.affiliation: Cumming School of Medicine, Division of Nephrology, University of Calgary, Alberta, Canada; Department of Community Health Sciences, University of Calgary, Calgary, Alberta, Canada. Electronic address: brenda.hemmelgarn@albertahealthservices.ca.
authors.forename: Brenda R
authors.initials: BR
authors.lastname: Hemmelgarn
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000416:Alberta / Q000453:epidemiology; D000419:Albuminuria / Q000453:epidemiology; D000925:Anticoagulants / Q000627:therapeutic use*; D001281:Atrial Fibrillation / Q000150:complications / Q000188:drug therapy* / Q000453:epidemiology; D002423:Cause of Death; D015331:Cohort Studies; D015897:Comorbidity; D003404:Creatinine / Q000378:metabolism; D005919:Glomerular Filtration Rate; D006470:Hemorrhage / Q000139:chemically induced; D006801:Humans; D002546:Ischemic Attack, Transient / Q000209:etiology / Q000517:prevention & control*; D009026:Mortality; D057216:Propensity Score; D051436:Renal Insufficiency, Chronic / Q000453:epidemiology / Q000378:metabolism*; D012189:Retrospective Studies; D020521:Stroke / Q000209:etiology / Q000517:prevention & control*; D014859:Warfarin / Q000627:therapeutic use*
chemical_list: D000925:Anticoagulants; D014859:Warfarin; D003404:Creatinine
keywords: Atrial fibrillation (AF); antithrombotic therapy; bleeding event; cardiovascular disease; chronic kidney disease (CKD); death; estimated glomerular filtration rate (eGFR); ischemic stroke; kidney function; major bleeding; stroke; transient ischemic attack (TIA); warfarin