In Reply We thank Van der Linden and colleagues for their interest in our article,1 which describes the long-term cardiovascular risk associated with continued use of enzyme-inducing antiseizure medications (eiASMs). With respect to our mediation analysis, we considered incident dyslipidemia as a binary mediator variable, as opposed to a continuous variable of low-density lipoprotein cholesterol or total cholesterol, given its direct clinical relevance as the threshold over which treatment is initiated. However, we agree that future efforts at exploring a dose-dependent mediation between absolute and relative increases in low-density lipoprotein cholesterol and total cholesterol compared with baseline (pre-eiASM) treatment levels is warranted to further elucidate this potential mechanism. To address confounding, the mediation analysis indeed controlled for baseline hypertension, along with age at epilepsy diagnosis, sex, type 2 diabetes, atrial fibrillation, social deprivation (Index of Multiple Deprivation), former or current smoker, and duration of epilepsy. We opted not to adjust for baseline use of lipid-lowering agents in this analysis because the mediating variable was an incident diagnosis of dyslipidemia. Also, by definition, no person had a myocardial infarction or a stroke at the point of exposure to dyslipidemia, given the outcome (which occurs temporally after the mediator) was incident cardiovascular disease.
Josephson CB, Keezer MR, Wiebe S. Inducers and Cardiovascular Risk—Potential Role for Lowered Drug Exposure—Reply. JAMA Neurol. 2022;79(4):419–420. doi:10.1001/jamaneurol.2022.0044
Artificial Intelligence Resource Center
Customize your JAMA Network experience by selecting one or more topics from the list below.