Use of nonsteroidal anti-inflammatory drugs among healthy people and specific cerebrovascular safety

Int J Stroke. 2014 Oct;9(7):943-5. doi: 10.1111/j.1747-4949.2012.00863.x. Epub 2012 Oct 23.

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.

Aims: 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.

Keywords: epidemiology; hemorrhage; stroke; stroke subtypes; treatment; vascular events.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Anti-Inflammatory Agents, Non-Steroidal / adverse effects*
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use
  • Brain Ischemia / epidemiology*
  • Cohort Studies
  • Denmark / epidemiology
  • Diclofenac / adverse effects
  • Diclofenac / therapeutic use
  • Humans
  • Ibuprofen / adverse effects
  • Ibuprofen / therapeutic use
  • Intracranial Hemorrhages / epidemiology*
  • Naproxen / adverse effects
  • Naproxen / therapeutic use
  • Odds Ratio
  • Proportional Hazards Models
  • Risk
  • Stroke / epidemiology*

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Diclofenac
  • Naproxen
  • Ibuprofen