Long-Term Dementia Risk and Warfarin Treatment in Patients with Atrial Fibrillation

A new analysis finds that patients who take warfarin for atrial fibrillation (AF) are more likely to develop dementia than people who take the drug for the long-term treatment of other conditions.

The new results — particularly when combined with those from an earlier study from the same team — suggest that part of the dementia risk associated with AF stems from long-term anticoagulation use and part of it stems from some other aspect of the condition.

Investigators analyzed outcomes for 10,537 warfarin users who suffered no dementia at baseline. After a mean follow-up of more than 5 years, the 4,460 cohort members who were AF patients (rather than the 5,868 who took warfarin for thromboembolism or the 209 who took it after receiving a mechanical heart valve) experienced higher rates of total dementia (5.8% versus 1.6%, P<0.0001), Alzheimer disease (2.8% versus 0.9%, P<0.0001), and vascular dementia (1.0% versus 0.2%, P<0.0001).

The study team then ran a second comparison designed to account for the fact that AF patients were older than other cohort members and suffered from higher rates of hypertension, diabetes, heart failure and stroke. They matched AF and non-AF patients and performed a propensity analysis on 6,030 patients. AF patients still suffered higher rates of total dementia (hazard ratio [HR], 2.42; 95% confidence interval [CI], 1.85—3.18; P<0.0001), Alzheimer’s disease (HR, 2.04; 95% CI, 1.40–2.98; P<0.0001) and senility (HR, 2.46; 95% CI, 1.58–3.86; P<0.0001).

“This study is supportive of our hypothesis that AF is independently associated with an increase dementia risk beyond that attributed to anticoagulation,” the study authors wrote in the Jounal of the American Heat Association. “AF stems from unique risk factors and is associated with a risk of both macro and micro emboli from the left atrium/appendage, as well as from other vascular sources that raise the risk of AF genesis… In addition, AF patients share the risks of all chronically anticoagulated patients but also have additive risk from embolic events.”

The investigators who performed the new study also noted that the efficacy of anticoagulation — i.e. the time each patient spent in the therapeutic zone &mdash; also effected dementia risk. Low time in the therapeutic zone was associated with greater dementia risk (compared to high time in the therapeutic zone) both for patients with AF (26—50% versus >75%: HR, 2.51; P=0.005) and other patients (≤25% versus >75%: HR, 3.92; P<0.0001).

Such findings support earlier conclusions by the same research team.

In that study, the investigators examined records from 2,605 AF patients and found that those who remained in the correct therapeutic range less than 25% of the time developed dementia 5.34 times as frequently as better medicated counterparts. Patients who kept within the therapeutic range 26% to 50% of the time were 4.1 times more likely to develop dementia. Patients who kept within the therapeutic range 51% to 75% of the time were 2.57 times more likely to develop dementia.

“This points to the possibility that dementia in atrial fibrillation patients is partly due to small repetitive clots and/or bleeds in the brain,” said principal investigator T. Jared Bunch, MD.