Long-term overtreatment with antiplatelet/anticoagulant therapy may increase the risk of dementia in AF patients


Atrial fibrillation patients who are receiving a combination of antiplatelet and anticoagulant therapy and are over treated with warfarin may be at an increased risk of dementia, according to a study presented at the American Heart Association’s Scientific Sessions (AHA;15–19 November, Chicago, USA).

Patients with atrial fibrillation are at higher risk of developing all forms of dementia; however, the mechanisms behind the association of this arrhythmia and dementia are unknown, says T Jared Bunch, lead author of the study (director of electrophysiology at the Intermountain Medical Center Heart Institute in Murray, USA).

“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,” says Bunch. “This may also result in micro bleeds in the brain that do not cause symptoms right away, but accumulate over time raising the risk of dementia.”

Bunch et al analysed retrospectively-in a four-year study-1,031 chronically anticoagulated patients with no history of dementia receiving warfarin (target International Normalised Ratio [INR] 2–3) and antiplatelet drugs (aspirin was used in >90% of cases) with no previous history of stroke, transient ischaemic attack or dementia for up to 10 years while on the drug combination. The patients were managed by the Intermountain Healthcare Clinical Pharmacist Anticoagulation Service.

The researchers found the percent time over anticoagulated (INR >3) significantly influenced dementia risk. Dementia was diagnosed in 2.7% of patients that had supratherapeutic INR levels <10% compared to 5.8% in those patients that had supratherapeutic INRs >25%. Bunch et al also found that patients with a higher percent of time with supratherapeutic INRs were more likely to have valvular heart disease, renal failure, a higher percent of CHADS 3-6 scores, and a prior bleed. After multivariate adjustment, those patients with percent times of over anticoagulation >25% were 2.5 times more likely to develop dementia compared to those with levels <10%.

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.

Most patients in the study were Caucasian; so researchers are not sure results would apply to other ethnic groups.

Bunch says that there is some good news in their findings noting that if a patient is on warfarin and he/she is well controlled, even if the patient needs an antiplatelet drug, the dementia risk is very low. “The message is for those people who are consistently using warfarin and the levels are too high, perhaps we need to look at a different strategy.”

Another important message, says Bunch, is that people that are starting to take aspirin need to make sure there is an indication for it. “A lot of people take aspirin thinking that this is good for the heart, but not everybody needs to be on aspirin,” he notes.

“Clinicians should think that if they are having trouble managing people with warfarin, and if they notice that it is consistently over-effective either they need to see their patients more frequently, educate them on the use of warfarin, or perhaps switch to a novel agent, which is more predictable. Unfortunately, there are not current studies looking at dementia risk with the novel agents. However, they reduce large brain injuries from strokes and bleeds in atrial fibrillation so we hope that these outcomes will translate to small micro events” he concludes.