title: Meta-analysis of dyspepsia and nonsteroidal antiinflammatory drugs.
abstract: OBJECTIVE
  Nonsteroidal antiinflammatory drug (NSAID) use is a known risk factor for gastrointestinal (GI) perforations, ulcers, and bleeds, but there are limited data on its association with the very common symptom of dyspepsia. Using published and unpublished data sources, we sought to determine estimates of the risks of dyspepsia associated with NSAIDs.
  
  
  METHODS
  We searched computerized databases (1966-1998) for primary studies of NSAIDs reporting on GI complications. We also obtained Food and Drug Administration (FDA) new drug application reviews for the 5 most common NSAIDs. We included studies reporting defined upper GI outcomes among subjects (>17 years old) who used oral NSAIDs for more than 4 days. Two reviewers evaluated 4,881 published titles, identifying 55 NSAID versus placebo randomized controlled trials (RCTs), 37 unpublished (FDA data) placebo-controlled RCTs; 86 NSAID versus NSAID RCTs (sample size >or=50); and 103 observational studies.
  
  
  RESULTS
  The majority of clinical trials were of good quality. Meta-regression identified an increased risk of dyspepsia for users of specific NSAIDs (adjusted odds ratio [OR] of indomethacin, meclofenamate, piroxicam = 2.8), and for high dosages of other NSAIDs (OR = 3.1), but not for other NSAIDs regardless of dosage (OR = 1.1). Dyspepsia was not reported as an outcome in the case control or cohort studies.
  
  
  CONCLUSIONS
  Clinical trial data indicate that high dosages of any NSAID along with any dosage of indomethacin, meclofenamate, or piroxicam increase the risk of dyspepsia by about 3-fold. Other NSAIDs at lower dosages were not associated with an increased risk of dyspepsia.
authors.affiliation: Cedars-Sinai Health System and Zynx Health Inc., Los Angeles, California 90212, USA. jofman@amgen.com
authors.forename: Joshua J
authors.initials: JJ
authors.lastname: Ofman
authors.forename: Catherine H
authors.initials: CH
authors.lastname: Maclean
authors.forename: Walter L
authors.initials: WL
authors.lastname: Straus
authors.forename: Sally C
authors.initials: SC
authors.lastname: Morton
authors.forename: Marc L
authors.initials: ML
authors.lastname: Berger
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Roth
authors.forename: Paul G
authors.initials: PG
authors.lastname: Shekelle
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects / Q000145:classification / Q000627:therapeutic use*; D004415:Dyspepsia / Q000139:chemically induced / Q000453:epidemiology*; D006801:Humans; D016032:Randomized Controlled Trials as Topic; D012307:Risk Factors
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal