The association between antiepileptic drug and HMG-CoA reductase inhibitor co-medication and cholesterol management in patients with epilepsy

Summary Purpose Pharmacokinetic interactions have been demonstrated in enzyme-inducing antiepileptic drugs (EIAEDs) and statins; however, their clinical significance is not well established. The purpose of this study was to evaluate the association of EIAEDs and non-enzyme-inducing antiepileptic drugs (NEIAEDs) on statin dose adjustments and low-density lipoprotein (LDL) cholesterol levels in patients with epilepsy. Methods Retrospective insurance claims from 2000 to 2006 from the Ingenix Impact (formerly Integrated Health Care Information Services) database were analyzed. Two cohorts were compared, EIAEDs + statin and NEIAEDs + statin: 1118 patients were analyzed (58% men; 66% aged >55 years); 506 (45%) initiated with an EIAED. Outcomes assessed included statin dose adjustments and, for a subset of subjects, risk of mean LDL >100 mg/dL during the 12-month follow-up period. Descriptive statistics were calculated and regression models estimated. Results Among the EIAED group, 72% initiated with phenytoin; among the NEIAED group, 57% initiated with gabapentin. For the EIAED group, the risk of upward statin dose adjustments was significantly greater (odds ratio = 1.36; P = 0.04) compared with the NEIAED group; similarly, the risk of having mean LDL >100 mg/dL was significantly greater (odds ratio = 41.22; P = 0.005) and increased during the follow-up period (+26.6 mg/dL; P = 0.001) for the EIAED group. Discussion This study suggests that concomitant use of EIAEDs and statins may be associated with reduced clinical effectiveness of statins. Patients with epilepsy who use EIAEDs and statins concomitantly may require greater vigilance for optimal cholesterol management.