title: Safety of valproic acid in patients with chronic obstructive pulmonary disease: a population-based cohort study.
abstract: OBJECTIVE
  Valproic acid is an anticonvulsant that also inhibits histone deacetylase (HDAC), a property that could worsen pulmonary function in patients with chronic obstructive pulmonary disease (COPD). The clinical significance of this property is unknown. We therefore compared the risk of COPD exacerbation in older patients with COPD commencing treatment with either valproic acid or phenytoin, an anticonvulsant that does not affect HDAC.
  
  
  METHODS
  We conducted a population-based retrospective cohort study of Ontario residents with COPD aged 66 years or older who started treatment with valproic acid or phenytoin between 1 April 1993 and 30 November 2012. The primary outcome was a hospital admission or emergency department visit for a COPD exacerbation within 240 days of drug initiation. A secondary outcome examined initiation of oral corticosteroids in the outpatient setting.
  
  
  RESULTS
  During the study period, we identified 4596 COPD patients who commenced valproic acid and 8478 who commenced phenytoin. Following multivariable adjustment, valproic acid did not increase the risk of the primary outcome (adjusted hazard ratio 1.00, 95% confidence interval 0.79 to 1.26). Although valproic acid was associated with a lower risk of initiating oral corticosteroids in the first thirty days following commencement of anticonvulsant therapy (adjusted hazard ratio 0.32; 95% confidence interval 0.21 to 0.49), no difference was observed during subsequent follow-up.
  
  
  CONCLUSIONS
  Among older patients with COPD, treatment with valproic acid does not increase the risk of adverse pulmonary outcomes relative to phenytoin. These findings suggest that valproate-induced HDAC inhibition is of little clinical relevance in this context.
authors: Department of Family and Community Medicine, St. Michael's Hospital, Toronto, Canada; Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, Canada; University of Toronto, Toronto, Canada; Institute for Clinical Evaluative Sciences, Toronto, Canada.
authors: Tony
authors: T
authors: Antoniou
authors: Zhan
authors: Z
authors: Yao
authors: Ximena
authors: X
authors: Camacho
authors: Muhammad M
authors: MM
authors: Mamdani
authors: David N
authors: DN
authors: Juurlink
authors: Tara
authors: T
authors: Gomes
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000927:Anticonvulsants / Q000008:administration & dosage / Q000009:adverse effects; D015331:Cohort Studies; D005260:Female; D006760:Hospitalization / Q000639:trends; D006801:Humans; D008297:Male; D011159:Population Surveillance / Q000379:methods; D029424:Pulmonary Disease, Chronic Obstructive / Q000175:diagnosis / Q000188:drug therapy* / Q000453:epidemiology*; D012189:Retrospective Studies; D014635:Valproic Acid / Q000008:administration & dosage / Q000009:adverse effects*
chemical_list: D000927:Anticonvulsants; D014635:Valproic Acid
keywords: chronic obstructive pulmonary disease; histone deacetylase; pharmacoepidemiology; propensity score; valproic acid
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