CHICAGO—Long-term overtreatment with warfarin given in combination with antiplatelet therapy may increase the risk of dementia in patients with atrial fibrillation, a new study suggests.
Researchers retrospectively analyzed patients who received warfarin plus aspirin or clopidogrel for up to 10 years.
And patients who had an international normalized ratio (INR) above the acceptable range more than 25% of the time had an increased risk of dementia.
T. Jared Bunch, MD, of the Intermountain Medical Center Heart Institute in Murray, Utah, presented these findings at the American Heart Association’s Scientific Sessions 2014 (abstract 13426).
“[W]e have to consider that long-term exposure to anticlotting drugs such as warfarin, if not well controlled, can significantly increase bleeding risk,” Dr Bunch said. “This may result in micro bleeds in the brain that don’t cause symptoms right away but accumulate over time, raising the risk of dementia.”
Dr Bunch and his colleagues studied 1031 patients with no previous history of stroke or dementia for up to 10 years while they received warfarin plus aspirin or clopidogrel.
Among patients who had an INR higher than 3 more than 25% of the time, 2.7% developed dementia.
The researchers adjusted their analysis for traditional stroke and bleeding risk factors and found that patients with supratherapeutic INR levels more than 25% of the time had more than double the risk of dementia compared to patients with supratherapeutic INR levels less than 10% of the time. The hazard ratio was 2.40 (P=0.04).
This increase is higher than what researchers found in a previous study of warfarin alone.
Previous research also suggested that patients with atrial fibrillation taking warfarin were more likely to develop dementia if their INRs were too high or too low.
From those results, the researchers concluded that brain injury from both small bleeds and blood clots is likely important in the development of dementia in patients with atrial fibrillation.
“Even at skilled centers, it’s very common to have INR outside the ideal range up to 40% of the time,” Dr Bunch noted. “And, over the years, there may be an accumulative negative impact on cognitive ability.”
