Risk of ischaemic stroke associated with antiepileptic drugs: a population-based case-control study in Catalonia

Cerebrovascular disorders have occurred more frequently in some Central Nervous System (CNS) disorders, such as epilepsy. Some CNS drugs have been associated with increased stroke risk. Our aim was to estimate the risk of ischaemic stroke in patients exposed to antiepileptic drugs (AED).

Population-based matched case-control study using SIDIAP database, based in electronic health records from primary healthcare from Catalonia, Spain. Cases were those patients with a registered diagnosis of first stroke during 2009-2014. Up to 10 controls were selected for each case and matched by sex, age, and geographic area and without a prior diagnosis of stroke. We considered global drug exposure to AED, past and current exposure and exposure in monotherapy to each AED.

2,865 cases and 19,406 controls were exposed to AED during the study period. Global exposure to levetiracetam [(OR_adj3.3, CI95 % 2.8-4.0)], phenytoin [OR_adj1.5, CI95 % 1.2-41.9)], and valproic acid [(OR_adj 1.3, CI95 % 1.1-1.6)], showed significantly association to ischaemic stroke that was also maintained with current exposure of levetiracetam [OR_adj4.1, CI95 % 3.3-5.2)] and valproic acid [OR_adj1.4, CI95 % 1.1-1.9)]. Current levetiracetam monotherapy showed a very high risk of ischaemic stroke [(OR_adj 5.1, CI95 % 3.7-6.9)].

Drugs used for other conditions than epilepsy (pregabalin, gabapentin) were the most used AED and both did not show a risk. Levetiracetam shows a risk for stroke even when assessed in current monotherapy. The lack of data regarding the link with diagnosis and severity in our study makes it necessary to conduct further studies to confirm or dismiss our results, focussing on levetiracetam.