Valproate attenuates the risk of myocardial infarction in patients with epilepsy: a nationwide cohort study

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Abstract
Purpose Patients with epilepsy have increased risk of myocardial infarction (MI). Valproate can exert anti-atherosclerotic effects. We therefore examined the risk of MI in patients with epilepsy receiving valproate. Methods Two cohorts of patients with valproate-treated epilepsy and sex- and age-matched individuals (controls) from the general Danish population were identified by individual-level-linkage of nationwide registries and followed for 10 years. The two cohorts comprised patients treated with valproate at baseline and valproate-naïve patients initiating treatment in the study period, respectively. The hazard ratios (HR) of MI and all-cause death were estimated by two different Cox proportional-hazard models; valproate treatment was analysed as a baseline categorical covariate in the first cohort and as a time-dependent exposure covariate in the second cohort. Results The two cohorts comprised 53 086 and 102 003 individuals, respectively. In the first cohort, the risk of MI was decreased (HR 0.75, 95% confidence interval 0.59−0.97) while the risk of all-cause death was increased (HR 2.11, 95% confidence interval 1.95−2.28), compared to the controls. In the second cohort, the risk of MI was decreased (HR 0.62, 95% confidence interval 0.53−0.73) while the risk of all-cause death was similar to the controls (HR 1.02, 95% confidence interval 0.97−1.07). Conclusions In this nationwide pharmacoepidemiological study, we found a consistent association between valproate treatment and a reduced risk of MI in patients with epilepsy. Copyright © 2010 John Wiley & Sons, Ltd.