title: Time dependent risk of gastrointestinal complications induced by non-steroidal anti-inflammatory drug use: a consensus statement using a meta-analytic approach.
abstract: OBJECTIVE
  To provide an updated document assessing the global, NSAID-specific, and time dependent risk of gastrointestinal (GI) complications through meta-analyses of high quality studies.
  
  
  METHODS
  An exhaustive systematic search was performed. Inclusion criteria were: RCT or controlled study, duration of 5 days at least, inactive control, assessment of minor or major NSAID adverse effects, publication range January 1985 to January 2003. The publications retrieved were assessed during a specifically dedicated WHO meeting including leading experts in all related fields. Statistics were performed conservatively. Meta-regression was performed by regressing NSAID adjusted estimates against study duration categories.
  
  
  RESULTS
  Among RCT data, indolic derivates provided a significantly higher risk of GI complications related to NSAID use than for non-users: RR = 2.25 (1.00; 5.08) than did other compounds: naproxen: RR = 1.83 (1.25; 2.68); diclofenac: RR = 1.73 (1.21; 2.46); piroxicam: RR = 1.66 (1.14; 2.44); tenoxicam: RR = 1.43 (0.40; 5.14); meloxicam: RR = 1.24 (0.98; 1.56), and ibuprofen: RR = 1.19 (0.93; 1.54). Indometacin users had a maximum relative risk for complication at 14 days. The other compounds presented a better profile, with a maximum risk at 50 days. Significant additional risk factors included age, dose, and underlying disease. The controlled cohort studies provided higher estimates: RR = 2.22 (1.7; 2.9). Publication bias testing was significant, towards a selective publication of deleterious effects of NSAIDs from small sized studies.
  
  
  CONCLUSIONS
  This meta-analysis characterised the "compound" and "time" aspects of the GI toxicity of non-selective NSAIDs. The risk/benefit ratio of such compounds should thus be carefully and individually evaluated at the start of long term treatment.
authors.affiliation: Santé Publique, Epidémiologie et Economie de la Santé, CHU, Bât B23, B-4000 Sart-Tilman, Belgium, Europe. florent.richy@ulg.ac.be
authors.forename: F
authors.initials: F
authors.lastname: Richy
authors.forename: O
authors.initials: O
authors.lastname: Bruyere
authors.forename: O
authors.initials: O
authors.lastname: Ethgen
authors.forename: V
authors.initials: V
authors.lastname: Rabenda
authors.forename: G
authors.initials: G
authors.lastname: Bouvenot
authors.forename: M
authors.initials: M
authors.lastname: Audran
authors.forename: G
authors.initials: G
authors.lastname: Herrero-Beaumont
authors.forename: A
authors.initials: A
authors.lastname: Moore
authors.forename: R
authors.initials: R
authors.lastname: Eliakim
authors.forename: M
authors.initials: M
authors.lastname: Haim
authors.forename: J-Y
authors.initials: JY
authors.lastname: Reginster
mesh_terms: D000368:Aged; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects*; D005767:Gastrointestinal Diseases / Q000139:chemically induced*; D006801:Humans; D008875:Middle Aged; D016032:Randomized Controlled Trials as Topic; D012044:Regression Analysis; D018570:Risk Assessment
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal