Association between nonsteroidal anti-inflammatory drugs and upper gastrointestinal tract bleeding/perforation: an overview of epidemiologic studies published in the 1990s

Arch Intern Med. 2000 Jul 24;160(14):2093-9. doi: 10.1001/archinte.160.14.2093.


Background: In the last decades, studies have estimated the upper gastrointestinal tract bleeding/perforation (UGIB) risk associated with individual nonsteroidal anti-inflammatory drugs (NSAIDs). Later analyses have also included the effect of patterns of NSAID use, risk factors for UGIB, and modifiers of NSAID effect.

Methods: Systematic review of case-control and cohort studies on serious gastrointestinal tract complications and nonaspirin NSAIDs published between 1990 and 1999 using MEDLINE. Eighteen original studies were selected according to predefined criteria. Two researchers extracted the data independently. Pooled relative risk estimates were calculated according to subject and exposure characteristics. Heterogeneity of effects was tested and reasons for heterogeneity were considered.

Results: Advanced age, history of peptic ulcer disease, and being male were risk factors for UGIB. Nonsteroidal anti-inflammatory drug users with advanced age or a history of peptic ulcer had the highest absolute risks. The pooled relative risk of UGIB after exposure to NSAIDs was 3.8 (95% confidence interval, 3.6-4.1). The increased risk was maintained during treatment and returned to baseline once treatment was stopped. A clear dose response was observed. There was some variation in risk between individual NSAIDs, though these differences were markedly attenuated when comparable daily doses were considered.

Conclusions: The elderly and patients with a history of peptic ulcer could benefit the most from a reduction in NSAID gastrotoxicity. Whenever possible, physicians may wish to recommend lower doses to reduce the UGIB risk associated with all individual NSAIDs, especially in the subgroup of patients with the greatest background risk.

Publication types

  • Review
  • Systematic Review

MeSH terms

  • Age Factors
  • Anti-Inflammatory Agents, Non-Steroidal / adverse effects*
  • Duodenal Ulcer / chemically induced*
  • Duodenal Ulcer / epidemiology
  • Epidemiologic Studies
  • Gastrointestinal Hemorrhage / chemically induced*
  • Gastrointestinal Hemorrhage / epidemiology
  • Humans
  • Incidence
  • Peptic Ulcer Perforation / chemically induced*
  • Peptic Ulcer Perforation / epidemiology
  • Risk Factors
  • Sex Factors
  • Stomach Ulcer / chemically induced*
  • Stomach Ulcer / epidemiology


  • Anti-Inflammatory Agents, Non-Steroidal