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The Prevention of Chronic NSAID Induced Upper Gastrointestinal Toxicity: A Cochrane Collaboration Metaanalysis of Randomized Controlled Trials

ALAA ROSTOM, GEORGE WELLS, PETER TUGWELL, VIVIAN WELCH, CATHERINE DUBÉ, and JESSIE McGOWAN

ABSTRACT.

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 µg/day was superior to 400 µg/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 µg/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 µg/day has been directly shown to reduce the risk of ulcer complications. (J Rheumatol 2000;27:2203–14)

Key Indexing Terms:

NONSTEROIDAL ANTIINFLAMMATORY DRUGS
COX-2 INHIBITORS
PEPTIC ULCER
GASTROINTESTINAL HEMORRHAGE
PROPHYLAXIS
MISOPROSTOL
H₂-RECEPTOR ANTAGONISTS
PROTON PUMP INHIBITORS
METAANALYSIS
SYSTEMATIC REVIEW