Abstract 13426: Percent Time With a Supratherapeutic Inr in Atrial Fibrillation Patients Using an Antiplatelet Agent is Associated With Long-term Risk of Dementia

Abstract

Background: Patients with atrial fibrillation (AF) are at higher risk of developing all forms of dementia. The mechanisms behind the association of AF and dementia are unknown. One possibility is that exposure to chronic microbleeds results in repetitive cerebral injury that is manifest by cognitive decline. We hypothesize that AF patients receiving antiplatelet therapy will display higher rates of dementia if coupled with a higher percentage of time exposed to over-anticoagulation. Methods: Chronically anticoagulated patients receiving warfarin (target INR 2-3) for AF and managed by the Intermountain Healthcare Clinical Pharmacist Anticoagulation Service (CPAS) with no history of dementia or stroke/TIA and receiving antiplatelet therapy were included. The primary outcome was the presence of dementia defined by neurology determined ICD-9 codes. Percent time with an INR above 3.0 was determined. Multivariable Cox hazard regression was utilized to determine dementia incidence by percentage categories of supratherapeutic INR. Results: A total of 1031 patients were studied. Of these, the categories of the mean percent time with an INR >3.0 were 25% (n=240). Patients with a higher percent of time with supratherapeutic INRs were more likely to have valvular heart disease, renal failure (Cr>2.0), a higher percent of CHADS 3-6 scores, and a prior bleed. Dementia was diagnosed in 2.7% of patients with supratherapeutic INR levels 25%, p=0.05. Those with a supratherapeutic INR >25% of the time were at an increased dementia risk throughout follow-up. After multivariate adjustment, those with levels >25% had significantly higher rates of dementia compared to those with levels <10% (HR 2.40, p=0.04). Discussion: In AF patients receiving antiplatelet and anticoagulant therapies, the percent of time exposed to over anticoagulation increases risk of dementia. These data support the possibility of chronic cerebral injury from microbleeds as a mechanism that underlies the association of AF and dementia.