Abstract
Objective: Both time in therapeutic range (TTR) for anticoagulation and depression are associated with dementia risk. However, it is unknown if depression impacts TTR or their combined effect on dementia risk. Methods: We studied 14,953 patients who were chronically anticoagulated with warfarin (target INR 2-3) for atrial fibrillation (AF), venous thromboembolism (VTE), or a mechanical heart valve and managed by the Intermountain Healthcare Clinical Pharmacist Anticoagulation Service from 2003 to 2015. We excluded patients with a diagnosis of dementia before or within the first six months of warfarin management. TTR was evaluated as a continuous variable and by categories: ≤25%, 26-50%, 51-75%, and >75%. We examined the association of depression to TTR using finite mixture modeling and utilized multivariable Cox hazard regression to determine the association of TTR and depression to 3-year dementia incidence. Results: Forty percent (n=6055) of patients were diagnosed with depression while on warfarin therapy. Patients with depression were younger, female, taking warfarin for VTE, and had more comorbidities. They also had a lower TTR compared to patients without depression; after adjustment for baseline differences, depressed patients had an average TTR decrease of 4% (p<0.0001), and were 1.3 times more likely to have TTR <50% than non-depressed patients (p<0.0001). During follow-up, 4.83% of patients received the diagnosis of dementia within 3-years. The 3-year risk of dementia was highest for patients with a ≤50% TTR regardless of depression status (Figure). This rate was more than two times the rate of dementia compared to those without depression and with TTR>75%. Conclusions: In patients managed for warfarin, depression is very prevalent and is associated with significant decreases in TTR. TTR appears to be the significant driver for increased 3-year dementia risk in these patients. Examining ways to improve TTR for patients with depression is warranted.
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