Abstracts

Rationale:
Research suggests that statins may reduce the risk of developing epilepsy after a stroke. However, this association may differ between sexes. As sex differences between men and women in this association is a potentially clinically important finding, effect modification by sex requires further exploration. Therefore, the primary objective of this study was to assess whether sex modifies the association between post-stroke statin use and stroke-related epilepsy. Our secondary objectives were to assess whether statin characteristics and other risk factors affect stroke-related epilepsy risk within groups defined by sex.

Methods:
We conducted a nested case-control study using linked health administrative datasets. Participants were included if they were discharged from inpatient treatment for an ischemic stroke, between the ages of 66 and 105, and did not have a history of epilepsy, seizure or epilepsy risk factors, or statin use. Patients with epilepsy were matched on age, sex, and month with up to ten controls who had not yet developed epilepsy. The index date was defined as the epilepsy diagnosis date for cases and their matched controls. To address our primary objective, we used a conditional logistic regression model to estimate the adjusted odds ratio for statin use in the 100 days prior to the index date between those who did and did not develop epilepsy, including an interaction term between sex and statin use. To address our secondary objectives, we estimated the odds ratios for statin use and all covariates within groups defined by sex and the adjusted odds ratios for statin characteristics (i.e., type and intensity) among statin users stratified by sex.

Results:
The final sample included 1,009 patients who developed epilepsy and 6,522 matched controls. We did not observe a statistically significant interaction between statin use and sex (p-value=0.07). In the stratified analysis, statin use did not significantly affect the risk of epilepsy in men or women. The adjusted odds ratios for selected potential risk factors are available in Table 1. Among statin users, there was a lower risk of epilepsy among women taking rosuvastatin compared to women taking atorvastatin (OR 0.70; 95% CI 0.51-0.95) (Table 2). There were no differences among male statin users.

Conclusions:
We did not observe statistically significant differences between statin users and non-users in epilepsy risk in our entire sample or when stratifying by sex. Many risk factors for stroke-related epilepsy were the same for men and women. However, alcohol abuse, depression or anxiety, and diabetes mellitus were associated with epilepsy only among men. Among female statin users, rosuvastatin users had a lower risk of developing stroke-related epilepsy than atorvastatin users.

Funding:
Jack Cowin Chair in Epilepsy Research at Western University