Abstracts

Rationale: HMG-CoA reductase inhibitors (statins) are metabolized through the Cytochrome P450 (CYP450) enzyme in the liver. The isoenzyme 3A4 is induced by certain antiepileptic drugs (AEDs). Many epileptic patients, especially in the geriatric population, take statins for co-morbid hyperlipidemia. We hypothesized that patients on enzyme inducing AEDs (EIAEDs) would have higher levels of total cholesterol and LDL as well as higher dose utilization when compared to patients on non-enzyme inducing AEDs (NEIAEDs). The second part of the study examined cholesterol levels of patient who were not taking any statins. 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 VAMC 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 were on at least one AED and simvastatin for 6 months prior to cholesterol levels being examined. Patients taking other classes of cholesterol lowering medications were excluded. Also, patients taking valproate, an inhibitor of 3A4, were excluded. Medication 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 123 consecutive patients who were taking simvastatin (10 mg - 80mg daily) and an AED, and 104 patients taking only an AED. These groups were further divided into patients on at least one EIAED and those on only NEIAEDs. The average daily dose of simvastatin was significantly higher (p<0.05) in the EIAED group at 45.38 (±3.01) mg compared to 35.34 (±2.57) mg in the NEIAED group. In addition, the EIAED group had a significantly higher total cholesterol (TC) and LDL levels compared to the NEIAED. There were 74% of patients taking EIAEDs at their goal LDL level compared to 86% in the NEIAED group. When comparing the patients who are not taking any cholesterol lowering medications, the EIAED group had significantly higher levels of TC and HDL compared to the NEIAED patients. Conclusions: This retrospective study demonstrates a significant difference in simvastatin doses between patients taking on EIAEDs and NEIAEDs. In addition, patients taking EIAEDs had a significantly higher level of TC and LDL compared to NEIAEDs. These findings suggest that the drug-interaction between EIAEDs and simvastatin might be clinically significant. In the control group of patients taking AEDs but not simvastatin, the data shows higher TC and HDL, but not LDL. Although TC levels were elevated in people taking EIAEDs chronically, as compared to those on NEIAEDs, EIAED patients had higher levels of the cardioprotective HDL cholesterol. Overall, effect of AEDs on cholesterol levels seems complex. More studies are needed to assess whether the risk for cardiovascular morbidity and mortality is increased in this patient population.