Abstracts

Rationale: Studies suggest that patients taking enzyme inducing (cytochrome P450) antiepileptic drugs (EIAEDs) and hepatically metabolized statins (HMS) show an increased clearance of statins, which may lower statin efficacy and subsequently increase cardiovascular event risk (Murphy, 1999; Khandwala, 2006). The objective of the current study was to evaluate whether concomitant use of EIAEDs and HMS is associated with increased cardiovascular events in epilepsy patients compared to patients on enzyme neutral AEDs (ENAEDs) and non hepatically metabolized statins (NHMS). Methods: A retrospective longitudinal analysis of a large electronic medical records (EMR) database for the years 1996 - 2009 was conducted. Patients (aged ≥ 12 years) diagnosed with epilepsy and using AEDs were selected and classified into 6 mutually exclusive groups (EIAED+HMS; EIAED+ NHMS; ENAED+HMS; ENAED+NHMS; EIAED only; ENAED only) based on concomitant statin use. Patients receiving multiple AEDs or switched from their index AED were removed. Using covariate-adjusted cox proportional hazard regression analyses, incidence and relative risk of a CVD event (composite measure based on: myocardial infarction, stroke, transient ischemic attack, congestive heart failure and angina) during the follow-up period among patients in the 6 AED/statin groups were assessed. Results: A total of 21,963 epilepsy patients using AEDs of which 19.5% also had evidence of statin use were included. Overall, the mean (SD) age of the cohort was 46 (18) years and over 55% were male. Patients receiving statins concomitantly were older (58 vs 42) and had higher prevalence of other risk factors for CVD like diabetes and hypertension. The mean follow-up time for the cohort was 2.1 years and ranged from 1.5 years for ENAED+NHMS to 2.4 years EIAED users. Of those patients receiving AEDs and statins concomitantly, any CVD event was observed among 11.3% of EIAED+HMS, 9.6% of ENAED+NHMS, 8.8% of EIAED+NHMS, and 8.7% of ENAED+NHMS users. Congestive heart failure was the most commonly observed CVD event among EIAED+HMS (4.7%), EIAED+NHMS (3.9%) and ENAED+ HMS (3.1%). The likelihood of a CVD event did not differ significantly between EIAED+NHMS (hazard ratio [HR]: 0.83; 95% confidence interval [CI]: 0.59-1.17), ENAED+HMS (HR:1.02; 95% CI: 0.82-1.27), ENAED+NHMS (HR:1.00; 95% CI: 0.58-1.71) and EIAED+HMS group (Reference group). Conclusions: The analysis findings suggest that concomitant use of enzyme inducing AEDs and hepatically metabolized statins was not associated with increased risk of CVD events during the follow-up period. Studies with longer follow-up duration are required to determine the impact of long-term concomitant use of enzyme inducing AEDs and statins on CVD events.