Enzyme-inducing antiseizure medication utilization in patients with epilepsy and vascular risk factors

Several lines of evidence have suggested that exposure to enzyme-inducing antiseizure medications (EIASMs) may result in the subsequent development of hyperlipidemia, a well-known risk factor for vascular disease. This may be an issue of concern particularly in the context of additional comorbid vascular risk factors. We therefore aimed to investigate trends of and associations with the use of these medications among adult patients with epilepsy.

The cross-sectional Medical Expenditure Panel Survey (MEPS) was interrogated to ascertain the prevalence of use of EIASMs by noninstitutionalized adult patients with epilepsy in the United States between the years 2004 and 2015. Any patient prescribed carbamazepine, phenytoin, phenobarbital, or primidone within a given year was defined as having been prescribed an EIASM. Trends over three-year epochs were evaluated with univariate logistic regression, while associations with demographic factors, vascular risk factors, and vascular disease were evaluated using a chi-square test corrected for survey design as well as multivariate logistic regression.

A total of 2281 (unweighted) patients were identified, representing 1,781,237 individuals. Between 2004 and 2015, 45.9% (95% confidence interval [CI]: 42.4%-49.4%) were prescribed EIASMs. Approximately one-quarter of patients aged 65 years and above used EIASMs compared with 18.5% of younger patients (odds ratio [OR]: 1.83, 95% CI = 1.27-2.65). Female patients (OR = 0.61, 95% CI = 0.47-0.79) and those with heart disease (OR: 0.63, 95% CI = 0.45-0.89) were significantly less likely to be prescribed EIASMs. Among those prescribed EIASMs, 38.9% had hypertension, 12.2% had diabetes, 61.6% were overweight or obese, 17.3% heart disease, 17.2% had a history of a cerebrovascular event, and 28.5% had diagnosed hyperlipidemia. Nonetheless, between 2004-2006 and 2013-2015, the odds of EIASM prescription decreased significantly (OR: 0.39, 95% CI: 0.28-0.55).

A substantial proportion of patients with comorbid vascular disease or vascular risk factors (e.g., hypertension and older age) is prescribed EIASMs. This could potentially increase patients' risk for subsequent negative outcomes such as cardiovascular or cerebrovascular disease. Though utilization of these medications has decreased, further efforts toward increasing use of newer antiseizure medications (ASMs) that are not associated with similar risks may be warranted.