CNS Drugs

, Volume 32, Issue 4, pp 367–376 | Cite as

Effect of Statin Intensity on the Risk of Epilepsy After Ischaemic Stroke: Real-World Evidence from Population-Based Health Claims

  • Fang-Ju Lin
  • Hung-Wei Lin
  • Yunn-Fang Ho
Original Research Article



Statins possess neuroprotective effects. However, real-world evidence supporting their utility in post-stroke epilepsy (PSE) prevention is limited.


The association between statin use, including timing of prescribing (pre-stroke vs post-stroke), type (lipophilicity, intensity of therapy) and dose intensity, and risk of developing PSE were investigated by studying Taiwanese health claims (2003–2013).


Patients with new-onset ischaemic stroke were identified. The main outcome was a diagnosis of epilepsy after ischaemic stroke. According to pre-stroke statin use, groups of current users, former users, and non-users were compared using ANOVA. An extended Cox regression model was utilized to estimate the hazard ratio (HR) of PSE, with post-stroke statin use and certain comedications as time-dependent variables. Serial sensitivity analyses were performed to ensure study robustness.


Of the 20,858 ischaemic stroke patients, 954 (4.6%) developed PSE. Post-stroke statin use (adjusted HR (aHR) 0.55; 95% confidence interval 0.46–0.67, p < 0.001), but not pre-stroke statin use was associated with a significantly reduced risk of developing PSE. A dose-response correlation was also observed between PSE risk reduction and quartiles of the statin cumulative defined daily dose (cDDD) (aHR 0.84, 0.67, 0.53, and 0.50 for the lowest, second, third, and highest quartiles of cDDD, respectively). Risk predictors and protectors against PSE were also characterized.


The post-stroke use of statins after ischaemic stroke was associated with PSE risk reduction in a cDDD-dependent manner. Further clinical studies on the potential applications of statins for PSE prophylaxis, particularly among at-risk patients, are warranted.


Compliance with Ethical Standards

This study was based on healthcare data from the National Health Insurance Research Database provided by the National Health Insurance Administration, Ministry of Health and Welfare, and previously managed by the National Health Research Institutes. The data founders and providers had no role in the study design, data analysis, data interpretation, or writing of the report.

Conflict of interest

Fang-Ju Lin, Hung-Wei Lin, and Yunn-Fang Ho declare no conflicts of interest.


No funding was received for the study.

Supplementary material

40263_2018_501_MOESM1_ESM.docx (31 kb)
Supplementary material 1 (DOCX 30 kb)


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Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Graduate Institute of Clinical Pharmacy, College of MedicineNational Taiwan UniversityTaipeiTaiwan
  2. 2.School of Pharmacy, College of MedicineNational Taiwan UniversityTaipeiTaiwan
  3. 3.Department of PharmacyNational Taiwan University HospitalTaipeiTaiwan

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