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.
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.
Authors: Pia Larsson; Niklas Bergh; Emma Lu; Erik Ulfhammer; Mia Magnusson; Karin Wåhlander; Lena Karlsson; Sverker Jern Journal: J Thromb Thrombolysis Date: 2013-02 Impact factor: 2.300
Authors: Pia Larsson; Erik Ulfhammer; Mia Magnusson; Niklas Bergh; Sebastian Lunke; Assam El-Osta; Robert L Medcalf; Per-Arne Svensson; Lena Karlsson; Sverker Jern Journal: PLoS One Date: 2012-02-20 Impact factor: 3.240
Authors: Ditte-Marie Bretler; Peter Riis Hansen; Jesper Lindhardsen; Ole Ahlehoff; Charlotte Andersson; Thomas Bo Jensen; Jakob Raunsø; Christian Torp-Pedersen; Gunnar Hilmar Gislason Journal: PLoS One Date: 2012-12-17 Impact factor: 3.240
Authors: Alex Dregan; Judith Charlton; Charles D A Wolfe; Martin C Gulliford; Hugh S Markus Journal: Pharmacoepidemiol Drug Saf Date: 2014-06-02 Impact factor: 2.890