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

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. Author Contributions: Margaret Fang, Alan Go, Elaine Hylek, and Daniel Singer contributed to study concept and design, data analysis and interpretation, and preparation of manuscript. Yuchiao Chang contributed to data analysis and interpretation, and preparation of manuscript. Lori Henault and Nancy Jensvold contributed to study concept and design and acquisition of subjects and data. Anticoagulation therapy with warfarin effectively reduces the risk of ischemic stroke associated with atrial fibrillation but also increases the risk for major hemorrhage. [1][2][3][4] Although previous randomized trials of warfarin for atrial fibrillation reported low rates of hemorrhage, these studies included few patients aged 80 and older and selected their patients more rigorously than in actual clinical practice. 1,5 It is uncertain whether the low bleeding rates observed in trial settings apply to patients with atrial fibrillation in usual clinical care. Prior studies have also provided conflicting evidence as to whether older age is an independent risk factor for warfarin-associated hemorrhage. 6-8 As increasing numbers of elderly patients take warfarin for atrial fibrillation, 9 more-precise data are needed on hemorrhage rates in the oldest patients. NIH Public AccessMost observational studies of warfarin did not specifically address the risk of hemorrhage in patients with atrial fibrillation. Studies generally included patients taking warfarin for m...

Death and Disability from Warfarin-Associated Intracranial and Extracranial Hemorrhages

“…As previously reported, the rate of thromboembolism occurring without warfarin therapy was 2.5 per 100 person-years in the overall ATRIA cohort 10 and even higher in other cohorts 2,[20][21][22] ; these rates are reduced by more than 50% by warfarin therapy. 10,23 This benefit exceeds the additional risk of warfarin-associated intracranial hemorrhage (0.47 per 100 person-years with warfarin therapy compared with 0.29 per 100 person-years without warfarin therapy), 10,24 and the balance of risk to benefit seems to favor the use of warfarin for the typical patient with atrial fibrillation. 2 Nevertheless, there are likely to be subgroups of patients with atrial fibrillation for whom this balance is less favorable, making further work to identify these subgroups critical to optimizing the use of warfarin at the individual and population levels.…”

“…Older age, elevated INR level, and history of ischemic stroke have all been identified as risk factors for intracranial hemorrhage, but because older age and prior stroke are also risk factors for ischemic stroke, additional investigation into unique risk factors for intracranial hemorrhage is clearly needed. 2,15,24 Modifiable measures, such as maintaining anticoagulation intensity within the therapeutic range of INR 2.0 to 3.0, can reduce but will not entirely remove the risk of bleeding associated with warfarin. 15,25 A study of Medicare patients with atrial fibrillation showed that a high fall risk was associated with an increased risk of intracranial hemorrhage, 16 although the high rate of ischemic stroke (13.7 per 100 person-years) among this subset of patients with a high fall risk made warfarin the preferred option for most patients.…”

2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS

“…[383][384][385]. Czynniki ryzyka udaru mózgu i czynniki ryzyka krwawienia są częściowo wspólne (por.…”

2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS

“…385 Myocardial Infarction 48) trial, 321 edoxaban 60 mg once daily and edoxaban 30 mg once daily (with dose reductions in certain patients, Table 13), were compared with adjusted-dose warfarin. 405 Edoxaban 60 mg once daily was non-inferior to warfarin ( Table 13).…”