title: Effects of epilepsy and selected antiepileptic drugs on risk of myocardial infarction, stroke, and death in patients with or without previous stroke: a nationwide cohort study.
abstract: OBJECTIVE
  Patients with epilepsy have increased morbidity and mortality. We evaluated the risk of myocardial infarction (MI), stroke, and death associated with epilepsy and examined if this risk was modified by treatment with antiepileptic drugs (AEDs).
  
  
  METHODS
  A cohort consisting of the Danish population was followed from January 1997 to December 2006. The risk of MI, stroke, cardiovascular death, and all-cause death associated with epilepsy was estimated by multivariable Cox proportional hazard models stratified for occurrence of previous stroke. AED use was determined at baseline, and risks associated with exposure to individual AEDs were examined in patients with epilepsy.
  
  
  RESULTS
  In patients without previous stroke, AED-treated epilepsy was associated with an increased risk of MI (hazard ratio [HR], 1.09; 95%CI, 1.00-1.19), stroke (HR, 2.22; 95%CI, 2.09-2.36), cardiovascular death (HR, 1.64; 95%CI, 1.57-1.72), and all-cause death (HR, 1.92; 95%CI, 1.86-1.97). Compared with carbamazepine monotherapy, valproate was associated with a decreased risk of MI (HR, 0.72; 95%CI, 0.59-0.87) and stroke (HR, 0.86; 95%CI, 0.76-0.96), oxcarbazepine and phenobarbital with increased risk of cardiovascular death (HR, 1.10; 95%CI, 1.02-1.19 and HR, 1.08; 95%CI, 1.00-1.17, respectively) and all-cause death (HR, 1.11; 95%CI, 1.05-1.18 and HR, 1.18; 95%CI, 1.12-1.25, respectively), and oxcarbazepine with increased risk of stroke (HR, 1.21; 95%CI, 1.10-1.34), in patients with epilepsy.
  
  
  CONCLUSIONS
  Patients with epilepsy exhibit increased risk of MI, stroke, cardiovascular death, and all-cause death. Compared with carbamazepine monotherapy, valproate may decrease, and oxcarbazepine and phenobarbital may increase, the risk of adverse cardiovascular events in these patients.
authors.affiliation: Department of Cardiology, Copenhagen University Hospital, Gentofte, Denmark. jo@heart.dk
authors.forename: Jonas Bjerring
authors.initials: JB
authors.lastname: Olesen
authors.forename: Steen Zabell
authors.initials: SZ
authors.lastname: Abildstrøm
authors.forename: Jesper
authors.initials: J
authors.lastname: Erdal
authors.forename: Gunnar H
authors.initials: GH
authors.lastname: Gislason
authors.forename: Peter
authors.initials: P
authors.lastname: Weeke
authors.forename: Charlotte
authors.initials: C
authors.lastname: Andersson
authors.forename: Christian
authors.initials: C
authors.lastname: Torp-Pedersen
authors.forename: Peter Riis
authors.initials: PR
authors.lastname: Hansen
mesh_terms: D000328:Adult; D000368:Aged; D000927:Anticonvulsants / Q000009:adverse effects*; D015331:Cohort Studies; D004827:Epilepsy / Q000150:complications / Q000188:drug therapy* / Q000401:mortality; D006801:Humans; D008875:Middle Aged; D009203:Myocardial Infarction / Q000139:chemically induced* / Q000401:mortality; D012307:Risk Factors; D020521:Stroke / Q000139:chemically induced* / Q000150:complications / Q000401:mortality
chemical_list: D000927:Anticonvulsants