[Prevention of NSAID induced gastroduodenal ulcers]

Non-steroidal anti-inflammatory drugs (NSAIDs) are important agents in the management of arthritic and inflammatory conditions, and are among the most frequently prescribed medications in North America and Europe. However, there is overwhelming evidence linking these agents to a variety of gastrointestinal (GI) toxicities.

To review the effectiveness of common interventions for the prevention of NSAID induced upper GI toxicity.

A literature search was conducted, according to the Cochrane methodology for identification of randomized controlled trials in electronic databases, including MEDLINE from 1966 to January 2000, Current Contents for 6 months prior to January 2000, Embase to February 1999, and a search of the Cochrane Controlled Trials Register from 1973 to 1999. Recent conference proceedings were reviewed and content experts and companies were contacted.

Randomized controlled clinical trials (RCTs) of prostaglandin analogues (PA), H2-receptor antagonists (H2RA) or proton pump inhibitors (PPI) for the prevention of chronic NSAID induced upper Gl toxicity were included.

Two independent reviewers extracted data regarding population characteristics, study design, methodological quality and number of patients with endoscopic ulcers, ulcer complications, symptoms, overall drop-outs, drop-outs due to symptoms. Dichotomous data was pooled using Revman V3.1. Heterogeneity was evaluated using a chi square test.

Thirty-three RCTs met the inclusion criteria. All doses of misoprostol significantly reduced the risk of endoscopic ulcers. Misoprostol 800 micrograms/day was superior to 400 micrograms/day for the prevention of endoscopic gastric ulcers (RR = 0.18, and 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 micrograms/day than 400 micrograms/day (p = 0.0012). Misoprostol was the only prophylactic agent documented to reduce ulcer complications. Standard doses of H2RAs 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 H2RAs and PPIs 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: 27-0.51 respectively for gastric ulcer), and were better tolerated than misoprostol.

Misoprostol, PPIs, and double dose H2RAs are effective at 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 micrograms/day has been directly shown to reduce the risk of ulcer complications.