Valproate attenuates the risk of myocardial infarction in patients with epilepsy: a nationwide cohort study.
OBJECTIVE
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.
Department of Cardiology, Gentofte University Hospital, Hellerup, Denmark. jo@heart.dk
Jonas Bjerring
JB
Olesen
Peter Riis
PR
Hansen
Steen Zabell
SZ
Abildstrøm
Charlotte
C
Andersson
Peter
P
Weeke
Michelle
M
Schmiegelow
Jesper
J
Erdal
Christian
C
Torp-Pedersen
Gunnar Hilmar
GH
Gislason
D000328:Adult; D000368:Aged; D000927:Anticonvulsants / Q000627:therapeutic use*; D016022:Case-Control Studies; D002423:Cause of Death; D016009:Chi-Square Distribution; D015331:Cohort Studies; D003718:Denmark / Q000453:epidemiology; D004827:Epilepsy / Q000150:complications / Q000188:drug therapy* / Q000401:mortality; D005260:Female; D019538:Health Care Surveys; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000209:etiology / Q000401:mortality / Q000517:prevention & control*; D016016:Proportional Hazards Models; D012042:Registries; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome; D014635:Valproic Acid / Q000627:therapeutic use*
D000927:Anticonvulsants; D014635:Valproic Acid