Statins for the Prevention of Post-Stroke Seizure and Epilepsy Development: A Systematic Review and Meta-Analysis

J Stroke Cerebrovasc Dis. 2021 Oct;30(10):106024. doi: 10.1016/j.jstrokecerebrovasdis.2021.106024. Epub 2021 Aug 23.

Abstract

Objectives: Cerebrovascular disease is the leading cause of seizures and incident epilepsy of known etiology in older adults. Statins have increasingly garnered attention as a potential preventive strategy due to their pleiotropic effects beyond lipid-lowering, which may include neuroprotective and anti-epileptogenic properties. We aim to assess the evidence on statin use for prevention of post-stroke early-onset seizures and post-stroke epilepsy.

Materials and methods: We conducted a systematic review and meta-analysis in accordance with PRISMA guidelines, which was prospectively registered with PROSPERO (CRD42019144916). PubMed and Embase were searched from database inception to 05/2020 for English-language, full-text studies examining the association between statin use in adults and development of early-onset seizures (≤7 days post-stroke) or post-stroke epilepsy. Pooled analyses were based on random-effects models using the inverse-variance method.

Results: Of 182 citations identified, 175 were excluded due to duplication or ineligibility. The 7 eligible publications were all cohort studies from East Asia or South America, with a total of 53,579 patients. Pre-stroke statin use was not associated with post-stroke epilepsy (3 studies pooled: OR 1.14, CI 0.91-1.42). However, post-stroke statin use was associated with lower risk of both early-onset seizures (3 studies pooled: OR 0.36, CI 0.25-0.53), and post-stroke epilepsy (6 studies pooled: OR 0.64, CI 0.46-0.88).

Conclusions: Review of 7 cohort studies suggested post-stroke, but not pre-stroke, statin use may be associated with reduced risk of early-onset seizures and post-stroke epilepsy. Further research is warranted to validate these findings in broader populations and better parse the temporal components of the associations.

Keywords: Epilepsy; Hydroxymethylglutaryl-CoA reductase inhibitors; Meta-analysis; Seizures; Statins; Stroke; Systematic review.

Publication types

  • Meta-Analysis
  • Systematic Review

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Anticonvulsants / adverse effects
  • Anticonvulsants / therapeutic use*
  • Brain / drug effects*
  • Brain / physiopathology
  • Epilepsy / diagnosis
  • Epilepsy / etiology
  • Epilepsy / physiopathology
  • Epilepsy / prevention & control*
  • Female
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / adverse effects
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use*
  • Male
  • Middle Aged
  • Protective Factors
  • Risk Assessment
  • Risk Factors
  • Seizures / diagnosis
  • Seizures / etiology
  • Seizures / physiopathology
  • Seizures / prevention & control*
  • Stroke / complications
  • Stroke / diagnosis
  • Stroke / drug therapy*
  • Stroke / physiopathology
  • Time Factors
  • Treatment Outcome

Substances

  • Anticonvulsants
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors