November 26, 2014
Dementia Risk Increases When AF Is Over-treated
With Drug Combination 

Chicago—The risk of dementia is increased when atrial fibrillation (AF) patients are over-treated over the long term with warfarin combined with certain antiplatelet therapies, according to a new study.

The research, presented recently at the American Heart Association’s Scientific Sessions 2014, found that micro bleeds sometimes developed in patients on the anticlotting drug plus antiplatelet therapy with aspirin or clopidigrel to prevent stroke.

“In AF patients receiving antiplatelet and anticoagulant therapies, the percent of time exposed to over anticoagulation increases risk of dementia,” the study states. “These data support the possibility of chronic cerebral injury from micro bleeds as a mechanism that underlies the association of AF and dementia.”

“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,” added lead author T. Jared Bunch, MD, director of electrophysiology at the Intermountain Medical Center 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.”

Included in the study were 1,031 patients with no previous history of stroke or dementia who were on the drug combination for up to 10 years and monitored by the Intermountain Healthcare Clinical Pharmacist Anticoagulation Service. The researchers documented how often monitoring tests indicated abnormally slow blood clotting times—International Normalized Ratio (INR) measurement above 3—which suggested that study subjects were receiving too much warfarin.

Results indicate that the 240 patients with INR greater than 3 on 25% or more of their monitoring tests were more than twice as likely to be diagnosed with dementia as patients whose tests showed overtreatment less than 10% of the time. Overall, dementia was diagnosed in 2.7% of the patients with supratherapeutic INR levels a fourth of the time or more, according to the results.

That increased risk is higher than the risk shown in research on warfarin alone, study authors note. Previous studies also found that AF patients taking warfarin were more likely to develop dementia if lab measurements of their clotting time were frequently too slow or too fast, hypothesizing brain injury from both small bleeds and clots was important in the development of dementia.

This study points out that patients overtreated a higher percent of time were more likely to have valvular heart disease, renal failure, a higher percent of CHADS 3-6 scores, and a prior bleed.

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

He suggested that, for patients with too-high INRs, alternatives for stroke prevention include “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.”

Most of the patients in this study were Caucasian; researchers say they aren’t sure results would be applicable to other ethnic groups.

U.S. Pharmacist Social Connect