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Published on: February 26, 2013
The association between kidney function and major bleeding in older adults with atrial fibrillation starting warfarin
Min Jun1, Matthew T James2, Braden J Manns2
1Department of Medicine, Division of Nephrology, University of Calgary, AB, Canada, T2N 2T9.
Insights
Older adults with atrial fibrillation on warfarin face higher major bleeding risks with reduced kidney function. This risk is most significant in the first 30 days of treatment, especially for gastrointestinal bleeding.
Area of Science:
- Geriatrics
- Nephrology
- Cardiology
Background:
- Atrial fibrillation (AF) is common in older adults.
- Warfarin is a widely used anticoagulant for AF.
- Kidney function impacts drug metabolism and clearance.
Purpose of the Study:
- To determine major bleeding rates in older adults with AF starting warfarin, stratified by kidney function.
- To assess the influence of estimated glomerular filtration rate (eGFR) on bleeding risk.
Main Methods:
- Retrospective cohort study of 12,403 older adults (≥66 years) with AF starting warfarin.
- Kidney function assessed via eGFR (mL/min/1.73 m²).
- Major bleeding events (hospital admission/ED visit) were recorded.
Main Results:
- 45% had eGFR <60 mL/min/1.73 m².
- 11.6% experienced major bleeding over median 2.1 years.
- Lower eGFR correlated with higher adjusted major bleeding rates (P<0.001), particularly within the first 30 days.
- Gastrointestinal bleeding risk increased significantly with reduced eGFR.
Conclusions:
- Reduced kidney function is associated with increased major bleeding risk in older adults with AF on warfarin.
- The highest risk is observed within the first 30 days of warfarin initiation.
- Careful risk-benefit assessment considering kidney function is crucial for these patients.
Objective:
To determine rates of major bleeding by level of kidney function for older adults with atrial fibrillation starting warfarin.
Design:
Retrospective cohort study.
Setting:
Community based, using province wide laboratory and administrative data in Alberta, Canada.
Participants:
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.
Main Outcome Measures:
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.
