Abstracts

Rationale: HMG-CoA reductase inhibitors, or statins, are the most commonly prescribed lipid lowering agents in the United States. Statin therapy has been shown to reduce cardiac mortality, a frequent co-morbidity in geriatric epilepsy. Cytochrome P450 (CYP450) in the liver, specifically isoenzyme 3A4, metabolizes simvastatin, atorvastain and lovastatin. Some anti-epileptic drugs (AEDs) induce the metabolism of CYP3A4, leading to an increased statin metabolism, lowering statin serum concentrations and half-life. It is not known whether this drug interaction leads to higher cholesterol, cardiovascular events, or higher statin dose utilization. The objective of our study was to examine drug utilization and cholesterol levels in epilepsy patients who were chronically taking AEDs and statins. We examined whether differences in statin drug utilization exist between patients taking EIAEDs and those taking Non-enzyme inducing AEDs (NEIAEDs).Methods: This study is a retrospective analysis of men and women veteran patients who attend an out-patient seizure clinic at the Audie L Murphy VA in San Antonio, TX. The subjects were taking AEDs for epilepsy and simvastatin for hyperlipidemia, the first line cholesterol lowering agent at the VA. The patients must have been on at least one AED and simvastatin for 6 months prior to cholesterol levels being drawn. Medications dosing and type were reviewed and cholesterol levels were analyzed. Comparisons in simvastatin dose and cholesterol levels were made between patients taking EIAEDs and NEIAEDs and were analyzed using the standard t test with unequal variance.Results: The retrospective analysis consisted of 105 patients, 102 men and 3 women who were taking simvastatin (10 mg - 80mg daily). Sixty-four patients were on EIAEDs and 41 were on only NEIAEDs. The average daily dose of simvastin was significantly higher (p<0.05) in the EIAED group at 46.1 (±3.14) mg compared to 34.9 (±3.13) mg in the NEIAED group (Table 1). Further analysis examined the difference in cholesterol levels and LDL in the two groups. The differences between total cholesterol and LDL levels between the 2 groups are seen in Table 2. The difference is not significant.Conclusions: The present retrospective study in a routine clinical care scenario demonstrates a significant difference in simvastatin doses between patients taking on EIAEDs and NEIAEDs, suggesting that patients on EIAEDs require larger doses of simvastatin for optimal cholesterol levels. Although the differences in total cholesterol levels and LDL between patients taking simvastatin and either EIAEDs or NEIAEDs was not significant, there was a trend for worse cholesterol lowering effect among patients taking EIAEDs despite taking on average a higher dose of simvastatin as compared to those taking NEIAEDs. The data suggests that the drug interaction between simvastatin and EIAEDs might be of clinical significance. Further studies are needed to assess whether this relatively silent drug-drug interaction increases the risk for cardiovascular morbidity and mortality.