The prevention of chronic NSAID induced upper gastrointestinal toxicity: a Cochrane collaboration metaanalysis of randomized controlled trials

J Rheumatol. 2000 Sep;27(9):2203-14.


Objective: To review the effectiveness of common interventions for the prevention of nonsteroidal antiinflammatory drug (NSAID) induced upper gastrointestinal (GI) toxicity.

Methods: Randomized controlled clinical trials (RCT) of prostaglandin analogs, H2-receptor antagonists (H2RA), or proton pump inhibitors (PPI) for the prevention of chronic NSAID induced upper GI toxicity were identified through electronic databases, the Cochrane control trials register, conference proceedings, and by contacting content experts and companies. Outcome measures investigated were endoscopic ulcers, ulcer complications, symptoms, overall dropouts, dropouts due to symptoms, and study quality.

Results: Thirty-four RCT met the inclusion criteria. All doses of misoprostol significantly reduced the risk of endoscopic ulcers. Misoprostol 800 microg/day was superior to 400 microg/day for the prevention of endoscopic gastric ulcers (RR 0.18, RR 0.38, respectively; p = 0.0055). A dose-response relationship was not seen with duodenal ulcers. Misoprostol caused diarrhea at all doses, although significantly more at 800 than 400 microg/day (p = 0.0012). Misoprostol was the only prophylactic agent documented to reduce ulcer complications. Standard doses of H2RA were effective at reducing the risk of endoscopic duodenal (RR 0.24, 95% CI 0.10-0.57) but not gastric ulcers (RR 0.73, 95% CI 0.50-1.09). Both double dose H2RA and PPI were effective at reducing the risk of endoscopic duodenal and gastric ulcers (RR 0.44, 95% CI 0.26-0.74 and RR 0.37, 95% CI 0.27-0.51, respectively, for gastric ulcer) and were better tolerated than misoprostol.

Conclusion: Misoprostol, PPI, and double dose H2RA are effective in preventing chronic NSAID related endoscopic gastric and duodenal ulcers. Lower doses of misoprostol are less effective and are still associated with diarrhea. Only misoprostol 800 microg/day has been directly shown to reduce the risk of ulcer complications.

Publication types

  • Meta-Analysis

MeSH terms

  • Adult
  • Aged
  • Anti-Inflammatory Agents, Non-Steroidal / toxicity*
  • Anti-Ulcer Agents / administration & dosage*
  • Anti-Ulcer Agents / adverse effects
  • Digestive System / drug effects*
  • Histamine H2 Antagonists / administration & dosage
  • Humans
  • Middle Aged
  • Peptic Ulcer / drug therapy*
  • Peptic Ulcer / prevention & control*
  • Prostaglandins, Synthetic / administration & dosage
  • Randomized Controlled Trials as Topic / statistics & numerical data*


  • Anti-Inflammatory Agents, Non-Steroidal
  • Anti-Ulcer Agents
  • Histamine H2 Antagonists
  • Prostaglandins, Synthetic