Increased risk of stroke and myocardial infarction in patients with epilepsy: A systematic review of population-based cohort studies

Objective: The objective of the study was to review the current epidemiological evidence about the relationship between epilepsy and increased risk of cardio- and cerebrovascular events. Methods: We systematically searched MEDLINE (from inception to 19th October 2018) to identify populationbased cohort studies evaluating the risk of subsequent stroke or myocardial infarction (MI) in patients with epilepsy without history of prior cerebrovascular disease in comparison with subjects without epilepsy. Results: A total of 16,641 records were screened, and 6 studies were included. Data on the risk of subsequent stroke and MI were provided by five and two studies, respectively. The adjusted hazard ratios ((adj)HRs) of subsequent ischemic stroke for patients with epilepsy ranged from 1.09 (95% confidence interval (CI): 1.00-1.19) to 2.85 (95% CI: 2.49-3.26). Two studies assessing the incidence of hemorrhagic stroke showed an increased risk in patientswith epilepsy (adjHR: 3.30; 95% CI: 2.46-4.43 and adjHR: 2.27; 95% CI: 1.80-2.85). The (adj)HRs of subsequent MI ranged between 1.09 (95% CI: 1.00 to 1.19) and 1.48 (95% CI: 1.31-1.67). Age, hypertension, MI, diabetes, hyperlipidemia, and arteriosclerosis were significantly associated with the increase in stroke risk. A gradient between the antiepileptic drug (AED) dose and risk of subsequent stroke was found. In comparison with carbamazepine (CBZ), oxcarbazepine (OXC) was associated with an increased risk of stroke and valproate (VPA) with a reduction in risk of stroke andMI, whereas no significant associations with vascular disease were found for phenobarbital (PB), lamotrigine (LMT), phenytoin (PHT), clonazepam (CLZ), and clobazam (CLB). Conclusions: Patients with epilepsy are at higher risk of subsequent stroke and MI in comparison with subjects without epilepsy. Although individual AEDs may carry different risks of cardio- and cerebrovascular disease, the clinical relevance of the metabolic effects of the enzyme-inducing AEDs is still uncertain. (C) 2019 Elsevier Inc. All rights reserved.