Warfarin Excess in AF Patients on Aspirin Ups Dementia Risk

Marlene Busko

November 17, 2014

CHICAGO, IL — Patients with atrial fibrillation who were taking an antiplatelet and were above the therapeutic range for warfarin a quarter of the time were more than twice as likely to be diagnosed with dementia as patients who were not overtreated in a 4-year study[1].

The antiplatelet agent was aspirin in more than 95% of cases and clopidogrel in the other cases.

Many patients with atrial fibrillation may be taking aspirin because they think it is "good for their health," Dr T Jared Bunch (Intermountain Medical Center, Murray, UT) told heartwire at the American Heart Association (AHA) 2014 Scientific Sessions. But if they are not taking it for a prescribed reason (because they have CAD or a stent), they should stop taking aspirin because it adds risk over time.

Clinicians should ask their patients if they are on warfarin and check to see if long-term warfarin and aspirin are really needed. "We often look at an AF patient the first time we see them to manage their risk of bleeding and stroke, [but] patients' risk of stroke and bleeding change over time, and their initial therapy may no longer be the ideal therapy," he noted.

Repeated small bleeds in the hippocampus, where memory is stored, may underlie the association between overanticoagulation and heightened risk of dementia, he suggested.

Aspirin and Warfarin: A Fine Balance

Dr T Jared Bunch

In a previous study, researchers reported that patients with atrial fibrillation who were under- or overtreated with warfarin had a greater risk of dementia, as shown by a U-shaped curve[2].

Patients with atrial fibrillation typically have comorbid cardiovascular conditions that require long-term exposure to both warfarin and an antiplatelet, putting them at risk of overanticoagulation and dementia, the researchers hypothesized.

In the current study, researchers enrolled 1031 patients with AF, but no dementia, stroke, or TIA, receiving warfarin (target international normalized ratio [INR] of 2 to 3) and antiplatelet therapy (aspirin in >90% of cases; clopidogrel in the rest). To eliminate the possibility of reverse causality, any patients with evidence of cognitive decline or dementia were excluded. The primary outcome was the presence of Alzheimer's disease, determined by a neurology consultation.

Patients were classed into three categories, depending on the percentage of time they were above an INR of 3. About a third of patients had an INR above 3 less than 10% of the time (374 patients); another third, 10% to 24% of the time (417 patients); and another third, 25% or more of the time (240 patients).

Patients with a higher percentage of time with supratherapeutic INRs were more likely to have valvular heart disease, renal failure (creatinine >2.0 mg/dL), a higher percent of CHADS2 3 to 6 scores, and a prior bleed.

Patients with warfarin levels above the target INR more than 25% of the time were at an increased dementia risk throughout follow-up.

After multivariable adjustment for traditional stroke and bleeding risk factors such as hypertension, patients with elevated INR levels more than 25% of the time had significantly higher rates of dementia compared with those with elevated levels less than 10% of the time (hazard ratio 2.40, P=0.04).

The patients in this study were closely followed and had their INR within the target range 70% of the time, "which is high, even for trials," Bunch said. Yet, "we're still seeing dementia."

The study was conducted before novel oral anticoagulants (NOACs) were commonly used. As a next step, the group plans to study the effect of NOACs on dementia among patients with atrial fibrillation. In other work, they also identified a unique genetic marker in some patients predisposed to early atrial fibrillation and stroke.

Bunch reported no disclosures.

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