Effects of long-term anti-seizure medication monotherapy on all-cause death in patients with post-stroke epilepsy: a nationwide population-based study in Taiwan

Abstract

Objective We aim to compare the effect of long-term anti-seizure medication (ASM) monotherapy on the risk of death and new ischemic stroke in patients with post-stroke epilepsy (PSE). Patients and methods We identified all hospitalized patients (≥ 20 years) with a primary diagnosis of ischemic or hemorrhagic stroke from 2001 to 2012 using the National Health Insurance Research Database in Taiwan. The PSE cohort were defined as the stroke patients (1) who had no epilepsy and no ASMs use before the index stroke, and (2) who had epilepsy and ASMs use after 14 days from the stroke onset. The patients with PSE receiving ASM monotherapy were enrolled and were categorized into phenytoin, valproic acid, carbamazepine, and new ASM groups. We employed the Cox regression model to estimate the unadjusted and adjusted hazard ratios (HRs) with 95 % confidence intervals (CIs) of death and new ischemic stroke within 5 years across all groups, using the new ASM group as the reference. Results Of 6962 patients with PSE using ASM monotherapy, 3917 (56 %) were on phenytoin, 1623 (23 %) on valproic acid, 457 (7 %) on carbamazepine, and 965 (14 %) on new ASMs. After adjusting for confounders, compared with new ASM users, phenytoin users had a higher risk of death in 5 years (HR: 1.64; 95 % CI: 1.06–2.55). On the other hand, all ASM groups showed a similar risk of new ischemic stroke in 5 years. Conclusions Among patients with PSE on first-line monotherapy, compared to new ASMs, use of phenytoin was associated with a higher risk of death in 5 years.

Impact of Seizure Recurrence on 1-Year Functional Outcome and Mortality in Patients With Poststroke Epilepsy

“…A long-term population-based study in the United States reported a mean mRS score of 3.3 in 35 patients after early or late seizures following an ischemic stroke, 9 which was comparable with this study. The relatively low proportion of female cases (38.4%) was similar to those in a nationwide populationbased study in Taiwan (37.4%) 25 and a single-center retrospective study in Italy (34.6%). 26 This was probably due to the higher risk of stroke 27,28 and PSE 3,28 in males.…”

Poststroke Seizure and Epilepsy: A Review of Incidence, Risk Factors, Diagnosis, Pathophysiology, and Pharmacological Therapies

“…LEV and LTG had superior tolerability compared to CBZ, but no differences in seizure freedom were noted. It should be noted that these results come from studies with relatively small sample sizes [50][51][52].…”

“…This confirms that the newer drugs have much more tolerable adverse and fewer side effects. Additionally, focal epileptic patients were better able to tolerate 2nd generation drugs LEV and LTG when compared to the 1st generation drug CBZ [50][51][52].…”

Lipid profile with eslicarbazepine acetate and carbamazepine monotherapy in adult patients with newly diagnosed focal seizures: post hoc analysis of a phase III trial and open-label extension study

“…16 Choice of ASM monotherapy in the post-stroke epilepsy setting has also been shown to affect the relative risks of subsequent cardiovascular and all-cause death. 17,18 Since epilepsy is a chronic condition, often requiring life-long ASM treatment, the impact of an ASM on CCV risk factors is an important consideration when choosing treatment in order to reduce the risk of stroke and myocardial infarction over the long term. 10 As a potent enzyme inducer, carbamazepine (CBZ) can lead to changes in lipid parameters via effects on enzymes involved in endogenous metabolic pathways.…”