Percent Time With a Supratherapeutic INR in Atrial Fibrillation Patients Also Using an Antiplatelet Agent Is Associated With Long-Term Risk of Dementia.
BACKGROUND
Patients with atrial fibrillation (AF) are at higher risk of developing dementia. AF patients treated with warfarin with poor time in therapeutic ranges are significantly more likely to develop dementia. AF patients are also frequently treated with antiplatelet agents due to coexistent vascular disease. We hypothesize that AF patients with anticoagulation and antiplatelet therapies will be at higher risk of dementia, particularly with chronic exposure 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) on concurrent antiplatelet agents with no history of dementia or stroke/TIA were included. The primary outcome was the presence of dementia defined by neurologist determined ICD-9 codes. Percent time with an INR>3.0 was determined and then compared by 3 strata <10% (n = 340), 10-24% (n = 417), ≥25% (n = 235). Multivariable Cox hazard regression was utilized to determine dementia incidence by percent time.


RESULTS
A total of 992 patients were studied. Patients with an INR>3 more than 25% of the time were 2.40 times more likely to develop dementia (P = 0.04). A comparison between < 10% group and 10-24.9% group with INR>3 indicated no difference in risk for the development of dementia (P = 0.74). The risk was significantly increased in patients using triple antithrombotic therapy, although the number of patients within this group was small.


CONCLUSIONS
In AF patients receiving antiplatelet and anticoagulant therapies, the percent of time exposed to over-anticoagulation increased dementia risk. These data support the possibility of chronic cerebral injury from microbleeds as a mechanism underlying the association of AF and dementia.
Intermountain Medical Center Heart Institute, Intermountain Medical Center, Murray, Utah, USA.
Victoria
V
Jacobs
Intermountain Medical Center Heart Institute, Intermountain Medical Center, Murray, Utah, USA.
Scott C
SC
Woller
Intermountain Medical Center Heart Institute, Intermountain Medical Center, Murray, Utah, USA.
Scott M
SM
Stevens
Intermountain Medical Center Heart Institute, Intermountain Medical Center, Murray, Utah, USA.
Heidi T
HT
May
Intermountain Medical Center Heart Institute, Intermountain Medical Center, Murray, Utah, USA.
Tami L
TL
Bair
Intermountain Medical Center Heart Institute, Intermountain Medical Center, Murray, Utah, USA.
Brian G
BG
Crandall
Intermountain Medical Center Heart Institute, Intermountain Medical Center, Murray, Utah, USA.
Michael
M
Cutler
Intermountain Medical Center Heart Institute, Intermountain Medical Center, Murray, Utah, USA.
John D
JD
Day
Intermountain Medical Center Heart Institute, Intermountain Medical Center, Murray, Utah, USA.
J Peter
JP
Weiss
Intermountain Medical Center Heart Institute, Intermountain Medical Center, Murray, Utah, USA.
Jeffrey S
JS
Osborn
Intermountain Medical Center Heart Institute, Intermountain Medical Center, Murray, Utah, USA.
Charles
C
Mallender
Intermountain Medical Center Heart Institute, Intermountain Medical Center, Murray, Utah, USA.
Jeffrey L
JL
Anderson
Intermountain Medical Center Heart Institute, Intermountain Medical Center, Murray, Utah, USA.
T Jared
TJ
Bunch
anticoagulation; antiplatelet agent; atrial fibrillation; cerebral bleed; dementia, microbleed