Comparative Effectiveness and Safety of Seizure Prophylaxis Among Adults After Acute Ischemic Stroke

Abstract

Background: Older adults occasionally receive seizure prophylaxis in an acute ischemic stroke (AIS) setting, despite safety concerns. There are no trial data available about the net impact of early seizure prophylaxis on post-AIS survival.

Methods: Using a stroke registry (American Heart Association's Get With The Guidelines) individually linked to electronic health records, we examined the effect of initiating seizure prophylaxis (ie, epilepsy-specific antiseizure drugs) within 7 days of an AIS admission versus not initiating in patients ≥65 years admitted for a new, nonsevere AIS (National Institutes of Health Stroke Severity score ≤20) between 2014 and 2021 with no recorded use of epilepsy-specific antiseizure drugs in the previous 3 months. We addressed confounding by using inverse-probability weights. We performed standardization accounting for pertinent clinical and health care factors (eg, National Institutes of Health Stroke Severity scale, prescription counts, seizure-like events).

Results: The study sample included 151 patients who received antiseizure drugs and 3020 who did not. The crude 30-day mortality risks were 219 deaths per 1000 patients among epilepsy-specific antiseizure drugs initiators and 120 deaths per 1000 among noninitiators. After standardization, the estimated mortality was 251 (95% CI, 190-307) deaths per 1000 among initiators and 120 (95% CI, 86-144) deaths per 1000 among noninitiators, corresponding to a risk difference of 131 (95% CI, 65-200) excess deaths per 1000 patients. In the prespecified subgroup analyses, the risk difference was 52 (95% CI, 11-72) among patients with minor AIS and 138 (95% CI, 52-222) among moderate-to-severe AIS patients. Similarly, the risk differences were 86 (95% CI, 18-118) and 157 (95% CI, 57-219) among patients aged 65 to 74 years and ≥75 years, respectively.

Conclusions: There was a higher risk of 30-day mortality associated with initiating versus not initiating seizure prophylaxis within 7 days post-AIS. This study does not support the role of seizure prophylaxis in reducing 30-day poststroke mortality.

Keywords: anticonvulsants; ischemic stroke; neurology; seizures.

Figure 1.. Selection of eligible patients with new acute ischemic stroke (AIS) ≥65 years, 2014–2021.

Describes the sampling process that resulted in a sample of 3,171 subjects, including patients ≥ 65 years at the time of new acute ischemic stroke admission, with available data in the EHR system and who had not received ASDs in the three months before admission.

Figure 2.. Crude and standardized survival curves by seizure prophylaxis initiation strategy during the first 30 days post-stroke admission

^a Blue: ASD initiated within seven days post-AIS admission. ^a Red: ASD not initiated within seven days post-AIS. ^b Blue: Strategy for ASD initiation within seven days post-AIS admission. ^b Red: Strategy for no initiation of ASD within seven days post-AIS admission. Shaded areas: 95% confidence intervals constructed using bootstrap with 500 replications.

Figure 2.. Crude and standardized survival curves by seizure prophylaxis initiation strategy during the first 30 days post-stroke admission

^a Blue: ASD initiated within seven days post-AIS admission. ^a Red: ASD not initiated within seven days post-AIS. ^b Blue: Strategy for ASD initiation within seven days post-AIS admission. ^b Red: Strategy for no initiation of ASD within seven days post-AIS admission. Shaded areas: 95% confidence intervals constructed using bootstrap with 500 replications.

Figure 3.. Standardized Survival Curves by ASD Initiation Strategy Across Categories of Age and Stroke Severity.

Blue: Strategy for ASD initiation within seven days post-AIS admission. Red: Strategy for no initiation of ASD within seven days post-AIS admission. Shaded areas: 95% confidence intervals constructed using bootstrap with 500 replications.

Figure 3.. Standardized Survival Curves by ASD Initiation Strategy Across Categories of Age and Stroke Severity.

Blue: Strategy for ASD initiation within seven days post-AIS admission. Red: Strategy for no initiation of ASD within seven days post-AIS admission. Shaded areas: 95% confidence intervals constructed using bootstrap with 500 replications.

Figure 3.. Standardized Survival Curves by ASD Initiation Strategy Across Categories of Age and Stroke Severity.

Blue: Strategy for ASD initiation within seven days post-AIS admission. Red: Strategy for no initiation of ASD within seven days post-AIS admission. Shaded areas: 95% confidence intervals constructed using bootstrap with 500 replications.

Figure 3.. Standardized Survival Curves by ASD Initiation Strategy Across Categories of Age and Stroke Severity.

Blue: Strategy for ASD initiation within seven days post-AIS admission. Red: Strategy for no initiation of ASD within seven days post-AIS admission. Shaded areas: 95% confidence intervals constructed using bootstrap with 500 replications.