title: Use of nonsteroidal anti-inflammatory drugs among healthy people and specific cerebrovascular safety.
abstract: BACKGROUND
  Nonsteroidal anti-inflammatory drugs can increase bleeding and thrombosis, but little is known about the cerebrovascular safety of these drugs, especially among healthy people.
  
  
  OBJECTIVE
  The aim of this study was to examine the risk of ischemic and hemorrhagic stroke associated with the use of nonsteroidal anti-inflammatory drugs in healthy people.
  
  
  METHODS
  By individual-level linkage of nationwide administrative registers in Denmark, information on hospital admissions, prescription claims, vital status, and cause of death were obtained. A cohort of healthy people without hospital admissions for five-years and no important prescription claims for two-years was selected. Case crossover and Cox proportional hazard models were used to analyze the relationship between nonsteroidal anti-inflammatory drug utilization and specific cerebrovascular risk (fatal or non-fatal ischemic or hemorrhagic stroke).
  
  
  RESULTS
  We selected 1,028,437 healthy individuals (median age 39 years). At least one nonsteroidal anti-inflammatory drug was claimed by 44·7% of the study population, and the drugs were generally used for a short period of time and in low doses. High-dose ibuprofen and diclofenac were associated with increased risk of ischemic stroke [hazard ratio 2·15 (95% confidence interval 1·66-2·79) and 2·37 (confidence interval 1·99-2·81), respectively]. Diclofenac was also associated with increased risk of hemorrhagic stroke and so was naproxen [hazard ratio 2·15 (confidence interval 1·35-3·42)].
  
  
  CONCLUSIONS
  In healthy individuals, use of commonly available nonsteroidal anti-inflammatory drugs such as ibuprofen, diclofenac, and naproxen was associated with increased risk of stroke.
authors.affiliation: Department of Cardiology, University Hospital Gentofte, Hellerup, Denmark; Duke Clinical Research Institute, Duke University Medical Center, Durham, NC, USA.
authors.forename: Emil L
authors.initials: EL
authors.lastname: Fosbøl
authors.forename: Anne-Marie Schjerning
authors.initials: AM
authors.lastname: Olsen
authors.forename: Jonas Bjerring
authors.initials: JB
authors.lastname: Olesen
authors.forename: Charlotte
authors.initials: C
authors.lastname: Andersson
authors.forename: Lars
authors.initials: L
authors.lastname: Kober
authors.forename: Christian
authors.initials: C
authors.lastname: Torp-Pedersen
authors.forename: Gunnar H
authors.initials: GH
authors.lastname: Gislason
mesh_terms: D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects* / Q000627:therapeutic use; D002545:Brain Ischemia / Q000453:epidemiology*; D015331:Cohort Studies; D003718:Denmark / Q000453:epidemiology; D004008:Diclofenac / Q000009:adverse effects / Q000627:therapeutic use; D006801:Humans; D007052:Ibuprofen / Q000009:adverse effects / Q000627:therapeutic use; D020300:Intracranial Hemorrhages / Q000453:epidemiology*; D009288:Naproxen / Q000009:adverse effects / Q000627:therapeutic use; D016017:Odds Ratio; D016016:Proportional Hazards Models; D012306:Risk; D020521:Stroke / Q000453:epidemiology*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D004008:Diclofenac; D009288:Naproxen; D007052:Ibuprofen
keywords: epidemiology; hemorrhage; stroke; stroke subtypes; treatment; vascular events