Warfarin, AF May Each Contribute to Dementia Risk in Atrial Fibrillation

Marlene Busko

May 05, 2016

SAN FRANCISCO, CA — In more than 10,000 patients with different diseases who were receiving warfarin therapy to prevent clots and stroke, those who had atrial fibrillation (AF) as opposed to thromboembolism or a mechanical heart valve were more likely to develop dementia. including Alzheimer's disease, during about a 7-year follow-up[1]. A total of 2.8% of patients with AF vs 0.9% of the other patients developed Alzheimer's disease.

Dr T Jared Bunch (Intermountain Medical Center Heart institute, Salt Lake City, UT) presented this study May 5, 2016 at the Heart Rhythm Society (HRS) 2016 Scientific Sessions.

The study confirmed that AF patients had more baseline risk factors for dementia (such as hypertension, diabetes, prior stroke) than non-AF patients. However, in a subgroup analysis that corrected for this, the patients with AF still had a higher risk of all types of dementia.

In addition, the risk of dementia was higher when warfarin was poorly controlled, regardless of whether or not the patients had AF.

This study shows that "we really have to be careful in our prescribing practices of anticoagulation," Bunch told heartwire from Medscape. "Patients on warfarin who show erratic biologic results . . . need to be transitioned to other agents, if possible, or to potential nonpharmacologic approaches," he said.

Studies such as this one are important as guideline writers grapple with the issue of prophylaxis with anticoagulants for low-risk patients with a CHADS score of 1 or a CHA2DS2-VASc score of 1 or 2 to determine how best to lower the risk of clots and stroke, while keeping patients safe from large bleeds requiring transfusion and repeated small brain bleeds.

Is It the Warfarin or the AF That Increases Risk of Dementia?

In previous research, the group found that Alzheimer's disease risk was more likely in younger patients with AF when warfarin levels were poorly controlled compared with older anticoagulated patients. They also reported that among patients who were taking a concomitant antiplatelet agent (mostly aspirin) as well as warfarin, those who spent more time in a supratherapeutic warfarin range were at increased risk of dementia.

But it was unclear whether AF increased risk of dementia, independent of the anticoagulant treatment strategy.

To investigate this, the researchers analyzed data from patients whose warfarin was managed by the Intermountain Healthcare Clinical Pharmacist Anticoagulation Service. They identified 10,537 patients with no dementia who had received warfarin prophylaxis in the past decade, including 4460 patients with AF, 5868 patients with thromboembolism (deep vein thrombosis or pulmonary embolism), and 209 patients with a mechanical heart valve.

Compared with the patients without AF, those with AF were older and had higher rates of hypertension, diabetes, prior MI, and prior stroke. The patients in the AF group were followed for a mean of 6.3 years, and the others were followed for a mean of 8.2 years, for an overall follow-up of about 7 years.

Patients with AF were 1.6 times more likely than other patients to develop dementia, which was diagnosed by a neurologist; they had higher rates of total dementia (5.8% vs 1.6%), Alzheimer's disease (2.8% vs 0.9%), and vascular dementia (1.0% vs 0.2%) (all P<0.0001).

For patients in both groups, the risk for dementia grew incrementally higher as time in therapeutic range (TTR) worsened.

In a propensity analysis of 3015 patients with AF and 3015 patients without AF with similar baseline characteristics, the patients with AF still had significantly higher rates of total dementia (5.2% vs 2.6%), Alzheimer's disease (2.4% vs 1.4%), and vascular dementia (0.9% vs 0.3%%).

Risk of Dementia in AF Patients vs Other Patients on Warfarin Therapy*

Outcome HR (95% CI) P
Total dementia 2.42 (1.85–3.18) <0.0001
Alzheimer's disease 2.04 (1.40–2.98) <0.0001
Vascular dementia 3.47 (1.62–7.42) 0.0001
*In about 7 years of follow-up

There was a threefold increased risk of dementia in the AF group that continued to increase with time.

"Anticoagulation clearly has a role as far as long-term brain health and viability," Bunch said. Based on the propensity analysis, "We learned as well that AF is an additive disease state, in that it increases risk beyond anticoagulation, so its management also becomes very important to lower dementia risk."

The authors acknowledge that this was an observational study and cannot determine cause and effect.

Bunch has no relevant financial relationships.

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