Risk of stroke associated with use of nonsteroidal anti-inflammatory drugs during acute respiratory infection episode

Pharmacoepidemiol Drug Saf. 2018 Jun;27(6):645-651. doi: 10.1002/pds.4428. Epub 2018 Apr 16.


Background: Previous studies suggested that acute respiratory infection (ARI) could trigger stroke and that use of nonsteroidal anti-inflammatory drugs (NSAIDs) was associated with increased risk of stroke. In many countries, NSAIDs have been widely used among patients with ARI or common cold for pain and fever relief. However, studies evaluating whether NSAIDs use during ARI episodes may further increase the risk of stroke were very limited.

Methods and results: During 2007 to 2011, 29 518 patients with an incident hospitalization of stroke were identified. The date of admission was defined as the index date. Using case-crossover design, we compared the following exposure status between the case period (1- to 7-d period before the index date) and matched control period (366- to 372-d period before the index date): NSAIDs use during ARI episodes, ARI episodes without NSAIDs use, NSAIDs use only, or no exposure. Multivariable conditional regression models were used to estimate odds ratios adjusting potential confounders. The results suggested that NSAIDs use during ARI episodes was associated with a 2.3-fold increased risk of stroke (ischemic: adjusted odds ratio, aOR 2.27, 95% confidence interval, 95% CI, 2.00-2.58; hemorrhagic: aOR 2.28, 95% CI, 1.71-3.02). We also determined that parenteral NSAIDs were associated with much higher risk of stroke in patients with ARI.

Conclusions: Nonsteroidal anti-inflammatory drugs use during ARI episodes, especially parenteral NSAIDs use, was associated with a further increased risk of stroke.

Keywords: epidemiology; nonsteroidal anti-inflammatory drugs; pharmacoepidemiology; respiratory infection; stroke.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease / therapy
  • Adult
  • Aged
  • Anti-Inflammatory Agents, Non-Steroidal / adverse effects*
  • Case-Control Studies
  • Cross-Over Studies
  • Databases, Factual / statistics & numerical data
  • Female
  • Humans
  • Male
  • Middle Aged
  • Odds Ratio
  • Respiratory Tract Infections / complications
  • Respiratory Tract Infections / drug therapy*
  • Risk Factors
  • Stroke / epidemiology*
  • Stroke / etiology
  • Taiwan / epidemiology
  • Young Adult


  • Anti-Inflammatory Agents, Non-Steroidal