Patients with Atrial Fibrillation Face Increased Risk of Dementia if Anticoagulant Therapy is Not within Recommended Dose Range

Patients treated with too much or too little warfarin for atrial fibrillation (AF) are significantly more likely to develop dementia than patients who maintain proper medication levels.

A new study by researchers from at the Intermountain Medical Center Heart Institute in Murray, Utah, found that patients who usually took too much or too little warfarin for atrial fibrillation (AF) were significantly more likely to develop dementia than patients who maintained proper medication levels.

Indeed, among the 2,693 patients whose records were examined by researchers at Intermountain Medical Center Heart Institute, those who remained in the correct therapeutic range less than 25% of the time developed dementia 4.5 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 2.5 times more likely to develop dementia.

“Our results from the study tell us two things,” said principal investigator Jared Bunch, MD, in a news release that accompanied the announcement of the study results. “First, with careful use of anticoagulation medications, the dementia risk can be reduced. Patients on warfarin need very close follow-up in specialized anticoagulation centers if possible to ensure their blood levels are within the recommended levels more often.”

“Second, these results also point to a potential new long-term consequence of dependency on long-term anticoagulation medications. In this regard, stroke prevention therapies do not require long-term anticoagulation medications and reducing the use of these drugs will hopefully lower dementia risk,” said Bunch, who presented the findings this month at the 2014 Annual Heart Rhythm Society Scientific Session in San Francisco.

Earlier research from Bunch and colleagues had shown that people with AF develop dementia at substantially higher rates than otherwise comparable people with no arrhythmias, but that work did not suggest any particular reason for the difference.

Bunch now believes that improper levels of warfarin — the anticoagulant that is commonly prescribed to people with AF — may be a large part of the problem.

“This points to the possibility that dementia in atrial fibrillation patients is partly due to small repetitive clots and/or bleeds in the brain,” he said.

The study included all patients managed by the Intermountain Healthcare Clinical Pharmacist Anticoagulation Service who had long-term warfarin prescriptions for AF but no history of dementia or stroke/TIA.

Some 54.4% of those patients were male, and their average starting age was 73.6 years. 23.2% had a history of cancer, and 13.5% a history of a significant bleed.

On average, patient times were in warfarin’s proper therapeutic range — an international normalized ratio (INR) between 2 and 3 — averaged 62.7% of the time ±22.9. Time below the zone (INR was < 2.0) averaged 25.9% ±19.7, and time above the zone (INR was >3.0) averaged 16.0% ±14.6.

In all, dementia was diagnosed in 111 (4.1%) patients.

After all adjustments, varying times in the therapeutic zone were associated with increased dementia risk (vs. patients who spent more than 75% in the zone) as follows: < 25%: HR=4.58, p< 0.0001; 26-50%: HR=4.14, p< 0.0001; 51-75%: HR=2.52, p< 0.0001.

Such findings, Bunch said, are significant, particularly given the patient numbers involved.

“The most common anticoagulant used worldwide is warfarin, and we now know that if warfarin doses are consistently too high or too low, one of the long-term consequences can be brain damage.”