Age and the risk of warfarin-associated hemorrhage: The anticoagulation and risk factors in atrial fibrillation study

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% Cl = 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.