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

Purpose: 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.