title: The association between kidney function and major bleeding in older adults with atrial fibrillation starting warfarin treatment: population based observational study.
abstract: OBJECTIVE
  To determine rates of major bleeding by level of kidney function for older adults with atrial fibrillation starting warfarin.
  
  
  METHODS
  Retrospective cohort study.
  
  
  METHODS
  Community based, using province wide laboratory and administrative data in Alberta, Canada.
  
  
  METHODS
  12,403 adults aged 66 years or more, with atrial fibrillation who started warfarin treatment between 1 May 2003 and 31 March 2010 and had a measure of kidney function at baseline. Kidney function was estimated using the Chronic Kidney Disease Epidemiology Collaboration equation and participants were categorised based on estimated glomerular filtration rate (eGFR): ≥ 90, 60-89, 45-59, 30-44, 15-29, <15 mL/min/1.73 m(2). We excluded participants with end stage renal disease (dialysis or renal transplant) at baseline.
  
  
  METHODS
  Admission to hospital or visit to an emergency department for major bleeding (intracranial, upper and lower gastrointestinal, or other).
  
  
  RESULTS
  Of 12,403 participants, 45% had an eGFR <60 mL/min/1.73 m(2). Overall, 1443 (11.6%) experienced a major bleeding episode over a median follow-up of 2.1 (interquartile range: 1.0-3.8) years. During the first 30 days of warfarin treatment, unadjusted and adjusted rates of major bleeding were higher at lower eGFR (P for trend <0.001 and 0.001, respectively). Adjusted bleeding rates per 100 person years were 63.4 (95% confidence interval 24.9 to 161.6) in participants with eGFR <15 mL/min/1.73 m(2) compared with 6.1 (1.9 to 19.4) among those with eGFR >90 mL/min/1.73 m(2) (adjusted incidence rate ratio 10.3, 95% confidence interval 2.3 to 45.5). Similar associations were observed at more than 30 days after starting warfarin, although the magnitude of the increase in rates across eGFR categories was attenuated. Across all eGFR categories, adjusted rates of major bleeding were consistently higher during the first 30 days of warfarin treatment compared with the remainder of follow-up. Increases in major bleeding rates were largely due to gastrointestinal bleeding (3.5-fold greater in eGFR <15 mL/min/1.73 m(2) compared with ≥ 90 mL/min/1.73 m(2)). Intracranial bleeding was not increased with worsening kidney function.
  
  
  CONCLUSIONS
  Reduced kidney function was associated with an increased risk of major bleeding among older adults with atrial fibrillation starting warfarin; excess risks from reduced eGFR were most pronounced during the first 30 days of treatment. Our results support the need for careful consideration of the bleeding risk relative to kidney function when assessing the risk-benefit ratio of warfarin treatment in people with chronic kidney disease and atrial fibrillation, particularly in the first 30 days of treatment.
authors: Department of Medicine, Division of Nephrology, University of Calgary, AB, Canada, T2N 2T9.
authors: Min
authors: M
authors: Jun
authors: Department of Medicine, Division of Nephrology, University of Calgary, AB, Canada, T2N 2T9 Department of Community Health Sciences, University of Calgary, Calgary, AB, Canada.
authors: Matthew T
authors: MT
authors: James
authors: Department of Medicine, Division of Nephrology, University of Calgary, AB, Canada, T2N 2T9 Department of Community Health Sciences, University of Calgary, Calgary, AB, Canada.
authors: Braden J
authors: BJ
authors: Manns
authors: Department of Medicine, Division of Nephrology, University of Calgary, AB, Canada, T2N 2T9 Department of Community Health Sciences, University of Calgary, Calgary, AB, Canada.
authors: Robert R
authors: RR
authors: Quinn
authors: Department of Medicine, Division of Nephrology, University of Calgary, AB, Canada, T2N 2T9 Department of Community Health Sciences, University of Calgary, Calgary, AB, Canada.
authors: Pietro
authors: P
authors: Ravani
authors: Department of Medicine, Division of Nephrology, University of Calgary, AB, Canada, T2N 2T9.
authors: Marcello
authors: M
authors: Tonelli
authors: The George Institute for Global Health, The University of Sydney, Sydney, Australia.
authors: Vlado
authors: V
authors: Perkovic
authors: Section of Nephrology, Baylor College of Medicine, Houston, TX, USA.
authors: Wolfgang C
authors: WC
authors: Winkelmayer
authors: Department of Medicine, Division of Nephrology, University of Calgary, AB, Canada, T2N 2T9.
authors: Zhihai
authors: Z
authors: Ma
authors: Department of Medicine, Division of Nephrology, University of Calgary, AB, Canada, T2N 2T9 Department of Community Health Sciences, University of Calgary, Calgary, AB, Canada Brenda.Hemmelgarn@albertahealthservices.ca.
authors: Brenda R
authors: BR
authors: Hemmelgarn
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000416:Alberta / Q000453:epidemiology; D000925:Anticoagulants / Q000009:adverse effects*; D001281:Atrial Fibrillation / Q000150:complications*; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects / Q000502:physiology; D006470:Hemorrhage / Q000139:chemically induced* / Q000453:epidemiology; D006801:Humans; D015994:Incidence; D008297:Male; D012044:Regression Analysis; D051436:Renal Insufficiency, Chronic / Q000150:complications / Q000503:physiopathology*; D012189:Retrospective Studies; D014859:Warfarin / Q000009:adverse effects*
chemical_list: D000925:Anticoagulants; D014859:Warfarin
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