Background: Antiepileptic drugs (AED) are widely used for the control of epilepsy but also for other indications such as migraine and neuropathic pain. Previous studies indicate that enzyme-inducing AED modify serum lipids and lipoproteins levels via the induction of cytochrome P450. The use of enzyme-inducing AED may therefore increase the risk of cardio- and cerebrovascular events.
Objectives: To assess the risk of ischemic stroke and myocardial infarction (MI) associated with the use of enzyme-inducing AED as compared to non-enzyme-inducing AED in a cohort of adult patients from the United Kingdom’s General Practice Research Database (GPRD).
Methods: We conducted a population-based cohort study with a nested case-control analysis, using the GPRD, a large computerised database of anonymized primary care medical records on a population of over 11 million patients enrolled with more than 650 general practices. Information collected includes demographic characteristics, lifestyle factors, medical diagnoses, prescriptions, and referrals to specialists and hospitals. The cohort was formed of all subjects in the GPRD aged 18 or older who received at least one prescription for an antiepileptic drug between January 1, 1990 and April 30, 2013. Cohort entry was taken as the date of the first new AED prescription. Subjects were followed until the date of their first outcome event i.e., stroke or MI, the date they transferred out of the practice, death, or end of the study period, whichever occurred first. For both outcomes, cases were identified as all subjects within our cohort with a first-time diagnostic code recorded at any time after cohort entry. The index date for the cases was defined as the calendar date of the first recorded stroke or MI. For each case, up to 10 controls were randomly selected among the cohort members in the risk sets defined by the case, after matching on age, sex, AED indication (epilepsy, pain, psychiatric disease, or other), date of cohort entry and duration of follow-up. Current use of AED was defined as any AED prescription within three months before the index date. Crude and adjusted incidence odds ratios of stroke and MI associated with current use of the various AED and their corresponding 95% confidence intervals were estimated using conditional logistic regression. In separate models, we assessed any variation in the risk of stroke and MI according to duration of AED use, and time since discontinuation of AED for past users.
Results: The cohort included 252 411 patients. The main indication for AED use at cohort entry was pain (48.6%) followed by epilepsy (14.8%). Among this cohort, 5069 stroke and 3636 MI were identified during follow-up. Risk estimates of stroke and MI associated with current AED use, duration of AED use and time since discontinuation will be presented at the conference.
Conclusion: This large population-based study will provide a comprehensive picture of the vascular risk associated with the different AED classes, therefore contributing to delineate the benefice/risk of these medications in in clinical practice.