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


  • Conflict of Interest: None of the authors has any conflicts of interest. All authors had access to the data and contributed to the manuscript in accordance with standard requirements for coauthorship.
  • Funding: This work was supported by an award from the American Heart Association-Pharmaceutical Roundtable and David and Stevie Spina.



Nonsteroidal anti-inflammatory drugs can increase bleeding and thrombosis, but little is known about the cerebrovascular safety of these drugs, especially among healthy people.


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.


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).


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)].


In healthy individuals, use of commonly available nonsteroidal anti-inflammatory drugs such as ibuprofen, diclofenac, and naproxen was associated with increased risk of stroke.