心房細動に対する治療が認知症リスクを上昇させる(Abstract 13426)

Long-term overtreatment with the anti-clotting drug warfarin, combined with antiplatelet therapy with aspirin or clopidigrel to prevent stroke, may raise the risk of dementia in people with atrial fibrillation, according to research presented at the American Heart Association's Scientific Sessions 2014.

Atrial fibrillation raises the risk of stroke and all common forms of dementia. The mechanisms behind the association of atrial fibrillation and dementia are unknown.

"The dual drug regimen is often used to prevent strokes in people with coronary artery disease or peripheral vascular disease, but we have to consider that long-term exposure to anti-clotting drugs such as warfarin, if not well controlled, can significantly increase bleeding risk," said T. Jared Bunch, M.D., lead author of the study and director of electrophysiology at the Intermountain Heart Institute in Murray, Utah. "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."

Researchers studied 1,031 patients with no previous history of stroke or dementia for up to 10 years while on the drug combination. After adjusting for traditional stroke and bleeding risk factors, patients with an International Normalized Ratio (INR) greater than 3.0 on 25 percent or more of their monitoring tests were more than twice as likely to be diagnosed with dementia than patients whose tests showed overtreatment less than 10 percent of the time (HR 2.40, p=0.04).  The increase is higher than what researchers found in a previous study of warfarin alone.  Patients with a higher percent of time with supratherapeutic INRs were also more likely to have valvular heart disease, renal failure (Cr>2.0), a higher percent of CHADS 3-6 scores, and a prior bleed.

Patients who had abnormally slow clotting times were considered to be receiving too much medication.

Researchers previously found that atrial fibrillation patients taking warfarin were more likely to develop dementia if lab measurements of their clotting time were frequently too slow (raising the risk of bleeding) or too fast (raising the risk of blood clots).  From those results they concluded that brain injury from both small bleeds and clots was important in the development of dementia in atrial fibrillation patients.

"Even at skilled centers, it's very common to have INR outside the ideal range up to 40 percent of the time, and over the years there may be an accumulative negative impact on cognitive ability," Bunch said.

"If your INRs are consistently too high, for stroke prevention your doctor may want to consider switching you to one of the newer anti-clotting drugs that is easier to regulate or a device placed into the heart that prevents clots from forming or exiting the area in the heart chamber where most clots develop in people with atrial fibrillation," he said.

Most patients in the study were Caucasian; so researchers aren't sure results would apply to other ethnic groups.

Co-authors are Heidi T. May, Ph.D.; Tami L. Bair, R.N.; Victoria Jacobs, N.P.; Brian G. Crandall, M.D.; J. Peter Weiss, M.D.; Jeffrey S. Osborn, M.D.; Charles Mallendar, M.D.; John D. Day, M.D.; Jeffrey L. Anderson, M.D.; Jeffrey L. Olson, M.D.; Katie Johanning; Yenh Long, Pharm.D.; Scott M. Stevens, M.D.; and Scott C. Woller, M.D.