Stroke, mortality, and competing risks: analyses in a large cohort of patients with atrial fibrillation
Ashburner, Jeffrey M.
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Patients with atrial fibrillation (AF) are at increased risk of stroke. Warfarin anticoagulation therapy reduces the incidence of stroke and increases the incidence of hemorrhagic events. This dissertation further informs the decision to use anticoagulation therapy in AF patients by examining outcomes in patients with major hemorrhages, further examination of stroke risk in diabetic patients with AF, and by evaluating the association between warfarin and stroke while accounting for competing risk events. These studies utilized data from the AnTicoagulation and Risk Factors In Atrial Fibrillation (ATRIA) and ATRIA-CVRN (Cardiovascular Research Network) (Study 1 only) studies which consist of patients from Kaiser Permanente Northern and Southern California. Study 1 examined short and long-term mortality in patients who experienced major gastrointestinal (GI) hemorrhages. In the ATRIA cohort, patients using and not using warfarin at the time of GI hemorrhage were equally likely to die within 30-days, while in ATRIA-CVRN, patients using warfarin were much less likely to die within 30-days (adjusted mortality rate ratio (aMRR): 0.33, 95% CI: 0.16-0.70). For longer-term mortality, both cohorts were consistent with a reduced mortality rate among patients whose GI hemorrhage occurred while using warfarin. Study 2 assessed the association between diabetes characteristics (duration of diabetes and glycemic control) and incidence of ischemic stroke among patients with AF and diabetes. Duration ≥ 3 years was associated with a large increase in rate of stroke (adjusted hazard ratio (aHR): 2.04, 95% CI: 1.27-3.26) compared to patients with duration < 3 years. Patients with the poorest glycemic control (hemoglobin A1c (HbA1c) values ≥ 9.0%) did not have an increased rate of ischemic stroke compared to patients with HbA1c < 7.0%. Study 3 evaluated the association between warfarin and thromboembolism in analyses that did and did not account for competing death events. In analyses not accounting for competing events, the adjusted HR was 0.61 (95% CI: 0.54-0.69), and after accounting for competing death events this association was attenuated (aHR: 0.87, 95% CI: 0.77-0.99). In summary, these studies add to the literature about the benefits of warfarin therapy and risk of stroke in patients with AF, findings that can improve decisions about use of anticoagulants in patients with AF.