Abstracts

Rationale: Pharmacokinetic interactions are recognized as potential confounders in optimizing epilepsy treatment. Some studies suggest that enzyme-inducing antiepileptic drugs (AEDs) lead to reduced bioavailability of HMG-CoA reductase inhibitors (statins) through induction of the cytochrome P450 pathway, which could compromise the clinical effectiveness of statins and possibly lead to increased risk of ischemic heart disease. The purpose of this study is to compare the association of CYP450 enzyme-inducing AEDs (EIAEDs) and CYP450 non-enzyme-inducing AEDs (NEIAEDs) on the prevalence and frequency of statin dose adjustments, as well as low-density lipoprotein (LDL) cholesterol levels, in epilepsy patients with concomitant use of AEDs and statins. Methods: Retrospective insurance claims from the Integrated Health Care Information Services database (11/1998-5/2006) were analyzed. The analysis included patients aged ≥18 years with ≥1 ICD-9 diagnosis of epilepsy or nonfebrile convulsions; ≥2 prescriptions for EIAED(e.g., phenytoin, phenobarbital, carbamazepine) or NEIAED (e.g., valproate, lamotrigine, gabapentin); and ≥2 prescriptions for a statin (atorvastatin, simvastatin, or lovastatin) filled within 31 days of AED initiation. Two cohorts were compared: (1) EIAED initiators + statin; and (2) NEIAED initiators + statin. Propensity scoring was used to control for differences in baseline characteristics (i.e., demographics, overall comorbidity burden, history of cardiovascular-related events, and history of serious seizures). Outcomes assessed included risk of upward statin dose adjustment, number of upward statin dose adjustments, and for a subset of subjects, mean LDL cholesterol and risk of mean LDL >100mg/dL during the 12-month follow-up period. Descriptive statistics and regressions models were used to examine the relationship between initiation with a P450-inducing AED and these outcomes. Results: 1,118 subjects were included in the analysis (58% male; 66% aged >55 years); 506 (45%) initiated with an EIAED. Both cohorts were similarly matched on baseline characteristics. Among EIAED initiators, 72% initiated with phenytoin; among NEIAED initiators, 57% initiated with gabapentin. EIAED patients’ risk of upward statin dose adjustments was significantly greater (OR=1.36; P=0.04), and the mean number of upward statin dose adjustments was also greater (0.3 vs. 0.2; P=0.04) when compared to patients on a NEIAED. For those on EIAEDs, the risk of mean LDL >100mg/dL was significantly greater (OR=41.22; P=0.005) and mean LDL was significantly increased during follow-up (+26.6mg/dL; P=0.001). A greater proportion of those initiating with an EIAED had a stroke during follow-up when compared to NEIAED initiators (21.5% vs. 13.9%; P=0.0008). Conclusions: This study suggests that concomitant use of EIAEDs and statins may be associated with clinically reduced effectiveness of statins. Patients with epilepsy who use enzyme-inducing AEDs concomitantly with statins may require increased statin dosing to maintain optimal cholesterol levels.