title: Sudden cardiac death is associated both with epilepsy and with use of antiepileptic medications.
abstract: OBJECTIVE
  Epilepsy is associated with increased risk for sudden cardiac death (SCD). We aimed to establish, in a community based study, whether this association is mediated by epilepsy per se, use of antiepileptic medications (AEMs), or both.
  
  
  METHODS
  We studied SCD cases and age/sex matched controls in a case-control study in a large scale general practitioners' research database (n=478 661 patients). SCD risk for symptomatic epilepsy (seizure <2 years before SCD), stable epilepsy (no seizure <2 years before SCD), and use of AEMs (any indication) was determined.
  
  
  RESULTS
  We identified 926 SCD cases and 9832 controls. Fourteen cases had epilepsy. Epilepsy was associated with an increased SCD risk (cases 1.5%, controls 0.5%; adjusted OR 2.8, 95% CI 1.4 to 5.3). SCD risk was increased for symptomatic epilepsy (cases 0.9%, controls 0.1%; adjusted OR 5.8, 95% CI 2.1 to 15.6), but not with stable epilepsy (cases 0.6%, controls 0.4%; adjusted OR 1.6, 95% CI 0.7 to 4.1). AEM use was found in 23 cases and was associated with an increased SCD risk (cases 2.5%, controls 0.8%; adjusted OR overall 2.6, 95% CI 1.5 to 4.3) among symptomatic epilepsy cases (cases 0.9%, controls 0.1%; adjusted OR 6.4, 95% CI 2.4 to 17.4) and non-epilepsy cases (cases 1.0%, controls 0.4%; adjusted OR 2.3, 95% CI 1.01 to 5.2). Increased SCD risk was associated with sodium channel blocking AEMs (cases 1.6%, controls 0.4%; adjusted OR 2.8, 95% CI 1.1 to 7.2), but not with non-sodium channel blocking AEMs. Carbamazepine and gabapentin were associated with increased SCD risk (carbamazepine: cases 1.1%, controls 0.3%; adjusted OR 3.2, 95% CI 1.1 to 9.2; gabapentin: cases 0.3%, controls 0.1%; adjusted OR 5.7, 95% CI 1.2 to 27.9).
  
  
  CONCLUSIONS
  Epilepsy and AEM use are both associated with increased SCD risk in the general population. Poor seizure control contributes to increased SCD risk in epilepsy, while sodium channel blockade contributes to SCD susceptibility in AEM users.
authors.affiliation: Department of Cardiology, Heart Center, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands Interuniversity Cardiology Institute Netherlands, Utrecht, The Netherlands Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands.
authors.forename: Abdennasser
authors.initials: A
authors.lastname: Bardai
authors.affiliation: Department of Cardiology, Heart Center, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Marieke T
authors.initials: MT
authors.lastname: Blom
authors.affiliation: Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands.
authors.forename: Charlotte
authors.initials: C
authors.lastname: van Noord
authors.affiliation: Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands.
authors.forename: Katia M
authors.initials: KM
authors.lastname: Verhamme
authors.affiliation: Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands Department of Medical Informatics, Erasmus Medical Center, Rotterdam, The Netherlands.
authors.forename: Miriam C J M
authors.initials: MC
authors.lastname: Sturkenboom
authors.affiliation: Department of Cardiology, Heart Center, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Hanno L
authors.initials: HL
authors.lastname: Tan
mesh_terms: D000368:Aged; D000927:Anticonvulsants / Q000009:adverse effects*; D016022:Case-Control Studies; D015897:Comorbidity; D016757:Death, Sudden, Cardiac / Q000209:etiology*; D004198:Disease Susceptibility; D004827:Epilepsy / Q000150:complications* / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality; D005260:Female; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D012042:Registries; D018570:Risk Assessment; D012307:Risk Factors; D026941:Sodium Channel Blockers / Q000009:adverse effects*; D013997:Time Factors
chemical_list: D000927:Anticonvulsants; D026941:Sodium Channel Blockers
keywords: ARRHYTHMIAS