Anti-epileptics linked to higher risk of stroke in Alzheimer’s disease patients

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Anti-epileptic drug use is associated with an increased risk of stroke among persons with Alzheimer’s disease, according to a study from the University of Eastern Finland. The risk did not differ between old and new antiepileptic drugs.

The risk of stroke was particularly elevated for the first three months of antiepileptic drug use, and remained elevated after accounting for several chronic disorders, socioeconomic position and use of concomitant medications.

According to another recent study from the same research group, persons with Alzheimer’s disease use antiepileptic drugs more often than persons without Alzheimer’s disease. The difference was not explained by epilepsy, and there was a considerable increase in antiepileptic drug use around the time when Alzheimer’s disease was diagnosed.

Up to 1% of population needs chronic antiepileptic treatment to control epilepsy. Other indications for antiepileptic drug use include neuropathic pain and dementia-related behavioural symptoms in persons with Alzheimer’s disease.

The present findings indicate that as persons with Alzheimer’s disease are particularly susceptible to adverse events, the use of antiepileptic drugs for other indications than epilepsy or neuropathic pain should be carefully considered in this vulnerable population.

The studies were based on the nationwide register-based MEDALZ cohort that includes all community-dwelling persons with clinically verified diagnosis of Alzheimer’s disease in Finland during 2005–2011 (70,718 people). Data on antiepileptic drug use was extracted from the Finnish Prescription Register. To assess the risk of stroke associated with antiepileptic drug use, each antiepileptic drug user was matched to a non-user.

The study was conducted at the University of Eastern Finland and funded by the Academy of Finland.

Abstract
Background: People with Alzheimer disease (AD) are more predisposed to seizures than older people in general, and use of antiepileptic drugs (AEDs) is more frequent. AED use has been linked to a higher risk of vascular events in the general population; however, it is not evident whether the same risk exists in people with AD. We assessed the risk of stroke associated with incident AED use among people with AD.
Methods and Results: The MEDALZ (Medication Use and Alzheimer’s Disease) cohort includes all Finnish people who received a clinically verified AD diagnosis (N=70718) from 2005 to 2011. People with previous strokes were excluded. For each incident AED user (n=5617) one nonuser was matched according to sex, age, and time since AD diagnosis. Analyses were conducted with Cox proportional hazards models and inverse probability of treatment weighting. Compared with nonuse, AED use was associated with an increased risk of stroke (inverse probability of treatment weighting hazard ratio (HR), 1.37; 95% confidence interval [CI], 1.07–1.74). The risk was strongest during the first 90 days (adjusted HR, 2.36; 95% CI, 1.25–4.47) of AED use. According to stroke type, the association was with ischemic strokes (inverse probability of treatment weighting HR, 1.34; 95% CI, 1.00–1.79) and hemorrhagic ones (inverse probability of treatment weighting HR, 1.44; 95% CI, 0.86–2.43). The stroke risk of users of older AEDs did not differ from that of the users of newer AEDs (adjusted HR, 1.04; 95% CI, 0.71–1.53).
Conclusions: AED use was related to an increased risk of stroke, regardless of AED type. Our results highlight caution in AED use in this vulnerable population.

Authors
Tatyana Sarycheva, Piia Lavikainen, Heidi Taipale, Jari Tiihonen, Antti Tanskanen, Sirpa Hartikainen, Anna‐Maija Tolppanen

Journal of the American Heart Association abstract

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