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Age and the Risk of Warfarin-Associated Hemorrhage: The Anticoagulation and Risk Factors In Atrial Fibrillation Study

Authors

  • Margaret C. Fang MD, MPH,

    1. From the *University of California at San Francisco, San Francisco, CaliforniaDivision of Research, Kaiser Permanente of Northern California, Oakland, CaliforniaGeneral Internal Medicine and Clinical Epidemiology Unit, Boston University School of Medicine, Boston, Massachusetts§Clinical Epidemiology Unit, Massachusetts General Hospital, Boston, Massachusetts.
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  • Alan S. Go MD,

    1. From the *University of California at San Francisco, San Francisco, CaliforniaDivision of Research, Kaiser Permanente of Northern California, Oakland, CaliforniaGeneral Internal Medicine and Clinical Epidemiology Unit, Boston University School of Medicine, Boston, Massachusetts§Clinical Epidemiology Unit, Massachusetts General Hospital, Boston, Massachusetts.
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  • Elaine M. Hylek MD, MPH,

    1. From the *University of California at San Francisco, San Francisco, CaliforniaDivision of Research, Kaiser Permanente of Northern California, Oakland, CaliforniaGeneral Internal Medicine and Clinical Epidemiology Unit, Boston University School of Medicine, Boston, Massachusetts§Clinical Epidemiology Unit, Massachusetts General Hospital, Boston, Massachusetts.
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  • Yuchiao Chang PhD,

    1. From the *University of California at San Francisco, San Francisco, CaliforniaDivision of Research, Kaiser Permanente of Northern California, Oakland, CaliforniaGeneral Internal Medicine and Clinical Epidemiology Unit, Boston University School of Medicine, Boston, Massachusetts§Clinical Epidemiology Unit, Massachusetts General Hospital, Boston, Massachusetts.
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  • Lori E. Henault MPH,

    1. From the *University of California at San Francisco, San Francisco, CaliforniaDivision of Research, Kaiser Permanente of Northern California, Oakland, CaliforniaGeneral Internal Medicine and Clinical Epidemiology Unit, Boston University School of Medicine, Boston, Massachusetts§Clinical Epidemiology Unit, Massachusetts General Hospital, Boston, Massachusetts.
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  • Nancy G. Jensvold MPH,

    1. From the *University of California at San Francisco, San Francisco, CaliforniaDivision of Research, Kaiser Permanente of Northern California, Oakland, CaliforniaGeneral Internal Medicine and Clinical Epidemiology Unit, Boston University School of Medicine, Boston, Massachusetts§Clinical Epidemiology Unit, Massachusetts General Hospital, Boston, Massachusetts.
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  • Daniel E. Singer MD

    1. From the *University of California at San Francisco, San Francisco, CaliforniaDivision of Research, Kaiser Permanente of Northern California, Oakland, CaliforniaGeneral Internal Medicine and Clinical Epidemiology Unit, Boston University School of Medicine, Boston, Massachusetts§Clinical Epidemiology Unit, Massachusetts General Hospital, Boston, Massachusetts.
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  • Results from this study were presented at the 2004 American Heart Association Scientific Session.

Address correspondence to Margaret C. Fang, MD, MPH, University of California, San Francisco, 533 Parnassus Ave., Box 0131, San Francisco, CA 94143. E-mail: mfang@medicine.ucsf.edu

Abstract

OBJECTIVES: To assess whether older age is independently associated with hemorrhage risk in patients with atrial fibrillation, whether or not they are taking warfarin therapy.

DESIGN: Cohort study.

SETTING: Integrated healthcare delivery system.

PARTICIPANTS: Thirteen thousand five hundred fifty-nine adults with nonvalvular atrial fibrillation.

MEASUREMENTS: Patient data were collected from automated clinical and administrative databases using previously validated search algorithms. Medical charts were reviewed from patients hospitalized were for major hemorrhage (intracranial, fatal, requiring ≥2 units of transfused blood, or involving a critical anatomic site). Age was categorized into four categories (<60, 60–69, 70–79, and ≥80), and multivariable Poisson regression was used to assess whether major hemorrhage rates increased with age, stratified by warfarin use and adjusted for other clinical risk factors for hemorrhage.

RESULTS: A total of 170 major hemorrhages were identified during 15,300 person-years of warfarin therapy and 162 major hemorrhages during 15,530 person-years off warfarin therapy. Hemorrhage rates rose with older age, with an average increase in hemorrhage rate of 1.2 (95% confidence interval (CI) 1.0–1.4) per older age category in patients taking warfarin and 1.5 (95% CI=1.3–1.8) in those not taking warfarin. Intracranial hemorrhage rates were significantly higher in those aged 80 and older (adjusted rate ratio=1.8, 95% CI=1.1–3.1 for those taking warfarin, adjusted rate ratio=4.7, 95% CI=2.4–9.2 for those not taking warfarin) than in those younger than 80.

CONCLUSION: Older age increases the risk of major hemorrhage, particularly intracranial hemorrhage, in patients with atrial fibrillation, whether or not they are taking warfarin. Hemorrhage rates were generally comparable with those reported in previous randomized trials, indicating that carefully monitored warfarin therapy can be used with reasonable safety in older patients.

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