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

Objective. To review the effectiveness of common interventions for the prev ention of nonsteroidal antiinflammatory drug (NSAID) induced upper gastroin testinal (GI) toxicity. Methods. Randomized controlled clinical trials (RCT) of prostaglandin analo gs, H-2-receptor antagonists (H(2)RA), or proton pump inhibitors (PPI) for the prevention of chronic NSAID induced upper GI toxicity were identified t hrough electronic databases, the Cochrane control trials register, conferen ce proceedings, and by contacting content experts and companies. Outcome me asures 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 misoprost ol significantly reduced the risk of endoscopic ulcers. Misoprostol 800 mu g/day was superior to 400 mu g/day for the prevention of endoscopic gastric ulcers (RR 0.18, RR 0.38, respectively; p = 0.0055). A dose-response relat ionship was not seen with duodenal ulcers. Misoprostol caused diarrhea at a ll doses, although significantly more at 800 than 400 mu g/day (p = 0.0012) . Misoprostol was the only prophylactic agent documented to reduce ulcer co mplications. Standard doses of H(2)RA were effective at reducing the risk o f endoscopic duodenal (RR 0.24, 95% CI 0.10-0.57) but not gastric ulcers (R R 0.73, 95% CI 0.50-1.09). Both double dose H(2)RA and PPI were effective a t reducing thr 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 ulce r) and were better tolerated than misoprostol. Conclusion. Misoprostol, PPI, and double dose H(2)RA are effective in preve nting chronic NSAID related endoscopic gastric and duodenal ulcers. Lower d oses of misoprostol are less effective and are still associated with diarrh ea. Only misoprostol 800 mu g/day has been directly shown to reduce the ris k of ulcer complications.