Risk for serious gastrointestinal complications related to use of nonsteroidal anti-inflammatory drugs. A meta-analysis

Ann Intern Med. 1991 Nov 15;115(10):787-96. doi: 10.7326/0003-4819-115-10-787.


Objective: To describe the relative risk for serious gastrointestinal complications due to non-aspirin nonsteroidal anti-inflammatory drug (NSAID) exposure among NSAID users as well as in selected subgroups.

Design: Overview and meta-analysis.

Data identification: A literature search of English-language studies examining the association between NSAIDs and adverse gastrointestinal events for the period 1975 to 1990 identified using MEDLINE and communicating with three internationally recognized experts.

Data analysis: A qualitative summary of study characteristics and a critical appraisal of study quality were done. The results of 16 primary studies were selected and combined statistically. Summary estimates were weighted by sample size and quality score.

Main results: The overall odds ratio of the risk for adverse gastrointestinal events related to NSAID use, summarized from 16 studies (9 case-control and 7 cohort) was 2.74 (95% Cl, 2.54 to 2.97). The summary odds ratios were as follows: elderly patients, (aged greater than or equal to 60 years), 5.52 (Cl, 4.63 to 6.60); patients under 65 years of age, 1.65 (Cl, 1.08 to 2.53); women, 2.32 (Cl, 1.91 to 2.82); and men, 2.40 (Cl, 1.85 to 3.11). The summary odds ratio for NSAID users receiving concomitant corticosteroids compared with NSAID users not receiving corticosteroids was 1.83 (Cl, 1.20 to 2.78). The summary odds ratio for the first gastrointestinal event was 2.39 (Cl, 2.16 to 2.65). The relative risk for a subsequent or unspecified gastrointestinal event was 4.76 (Cl, 4.05 to 5.59). The summary odds ratio for less than 1 month of NSAID exposure was 8.00 (Cl, 6.37 to 10.06); for more than 1 month but less than 3 months of exposure, the summary odds ratio was 3.31 (Cl, 2.27 to 4.82); and for more than 3 months of exposure, the summary odds ratio was 1.92 (Cl, 1.19 to 3.13).

Conclusions: Users of NSAIDs are at approximately three times greater relative risk for developing serious adverse gastrointestinal events than are nonusers. Additional risk factors include age greater than 60 years, previous history of gastrointestinal events, and concomitant corticosteroid use. Another possible risk factor is the first 3 months of NSAID therapy. The risk for serious gastrointestinal events appears to be equal among men and women. These data represent summary statistics from 16 studies and cannot be considered generalizable to all NSAID users.

Publication types

  • Meta-Analysis

MeSH terms

  • Anti-Inflammatory Agents, Non-Steroidal / adverse effects*
  • Case-Control Studies
  • Cohort Studies
  • Gastrointestinal Diseases / chemically induced*
  • Humans
  • Meta-Analysis as Topic
  • Odds Ratio
  • Risk


  • Anti-Inflammatory Agents, Non-Steroidal