Abstracts

Rationale: Enzyme-inducing anticonvulsants (or antiepileptic drugs, AEDs) are known to elevate serum lipids, but the clinical significance of this effect remains uncertain and is hard to measure. We reasoned that receiving a new diagnosis of hyperlipidemia may be considered a good proxy for clinically significant elevation of lipids. We therefore sought to determine how often such a diagnosis was obtained in patients who were newly diagnosed with epilepsy and started on inducing or non-inducing AEDs. Methods: We obtained data from the Truven MarketScan administrative claims database for commercial insurance and Medicare enrollees from 2005-2009, encompassing 951,991 individuals. For this study, we included subjects over age 18 who had had continuous coverage and enrollment in the database for 12 months prior (to ensure they had not carried a previous seizure diagnosis) with a new diagnosis of epilepsy (345.x) or seizure (780.3x) who were newly started on an AED for at least 6 months. We required an admission for either of the aforementioned codes, a single inpatient or outpatient service with an epilepsy code, or two distinct days of inpatient or outpatient services with the seizure code for inclusion. We excluded those who already had a hyperlipidemia diagnosis, were taking a lipid-lowering agent, or were already taking an AED (other than gabapentin or pregabalin, as these drugs are used far more often for pain than for seizures). Subjects were divided into those started on an inducing AED (phenytoin, carbamazepine, phenobarbital, primidone), or a non-inducing AED (all others). Subjects were followed until loss of coverage, change in AED class, or gap in medication possession of  >30 days. The primary outcome measure, a new diagnosis of hyperlipidemia (272.0x - 272.4x), was modeled by logistic regression to evaluate its association with the use of inducing AEDs. Results: 11,783 subjects were included in the analysis, of whom 9064 (77%) were prescribed non-inducing AEDs and 2719 (23%) were prescribed inducing AEDs. Inducing AED prescription was significantly positively correlated with male gender and increasing age (p<0.001 for each). New hyperlipidemia diagnoses were also positively correlated with male gender (OR 1.17, 95% CI 1.05-1.31, p=0.005) and increasing age (OR 1.18 for each 10 year increase, 95% CI 1.15-1.22, p<0.001). New hyperlipidemia diagnoses were seen in 432 (15.9%) of the patients started on inducing AEDs and 1055 (11.6%) of the patients started on non-inducing AEDs (p<0.001). After accounting for age and gender as covariates, inducing AED prescriptions were still associated with a 24% higher odds of a subsequent diagnosis of hyperlipidemia (OR 1.24, 95% CI 1.10 - 1.41, p<0.001). Conclusions: In this preliminary analysis, the use of enzyme-inducing AEDs in patients with newly diagnosed epilepsy was associated with a significant 24% increase in likelihood of subsequent new diagnoses of hyperlipidemia. This suggests that the lipid-elevating properties of these agents are of genuine clinical importance, as clinical hyperlipidemia would be expected to materially increase the risk of endpoint vascular disease of the heart, brain, and limbs. It also suggests that the use of these agents is of economic importance, in that they lead to other associated costs (e.g. monitoring and treatment for elevated lipids) more frequently than the use of non-inducing AEDs. Further analysis of our data to account for additional covariates will be performed. Funding: This study is funded by an investigator-initiated grant from UCB.