Prevention of nonsteroidal anti-inflammatory drug-induced gastrointestinal mucosal injury - A meta-analysis of randomized controlled clinical trials

Background: The policy of prevention of nonsteroidal anti-inflammatory drug (NSAID)-induced gastrointestinal mucosal injury is still a matter of discussion. Indeed, no consensus exists as to whether cotherapy with histamine type 2 (H-2) blockers or misoprostol is cost-effective. Methods: Placebo-controlled randomized clinical trials on the use of H-2 blockers or misoprostol, as preventive agents (published between January 1970 and December 1994), were identified through MEDLINE and reference lists from literature reviews. Crude rates of endoscopic lesions with shortterm (<2 weeks) and long-term (>4 weeks) NSAID treatment were systematically assessed by 3 independent observers based on the intention-to-treat principle. The method of DerSimonian and Laird was used for pooling data. Heterogeneity was evaluated by using the Q statistic and the plots described by L'Abbe and colleagues. Results: Twenty-four trials met the criteria for entry into the study. Gastric ulcer was found to be significantly reduced by misoprostol-both in short-term (pooled rate difference [RD], -13%; 95% confidence interval [CI], -26% to -1%) and long-term (RD, -8%; 95% CI, -18% to -1%) NSAID treatment-but not by H-2 blockers. The risk for duodenal ulcer was significantly reduced by H-2 blockers (RD, -2%; 95% CI, -5% to -0.2%) and by misoprostol (RD, -3%; 95% CI, -6% to -0.1%) in long-term but not in short-term administration. Conclusions: The use of misoprostol, but not that of H-2 blockers, was beneficial in the prevention of NSAID-induced gastric ulcers. The number of patients to be treated to prevent 1 gastric ulcer with short- and long-term NSAID treatment is 11 and 15, respectively, for an intermediate baseline risk of 10%. Misoprostol and H-2 blockers were beneficial in the long-term prevention of duodenal ulcers; misoprostol or H-2 blockers in the shortterm prevention of duodenal ulcers remains to be confirmed.