Supporting Evidence. The literature search identified one trial that assessed the effect of any agent on preventing clinically detectable upper gastrointestinal toxicities from NSAIDs. This large, multicenter, randomized, double-blind, placebo-controlled trial evaluated the occurrence of serious gastrointestinal side effects among nonselective NSAID users who were randomly assigned to receive misoprostol or placebo in addition to their usual nonselective NSAID (59). The 8843 participants (mean age, 68 years) were monitored for gastrointestinal complications. During the 2 years of the study, 25 serious gastrointestinal events were reported among the 4404 patients in the misoprostol group and 42 serious gastrointestinal events were reported among the 4439 patients in the placebo group [P < 0.05 for between-group comparisons]. Using multiple logistic regression modeling, the study authors evaluated the effects of several patient factors, as well as the effect of treatment, on the risk for serious gastrointestinal events. They identified the following risk factors for gastrointestinal bleeding: 1) age at least 75 years (odds ratio, 2.48 [CI, 1.48 to 4.14]], 2) history of peptic ulcer (odds ratio, 2.29 [CI, 1.28 to 4.12]], 3) history of gastrointestinal bleeding (odds ratio, 2.56 [CI, 1.30 to 5.03]], and 4) history of heart disease (odds ratio, 1.84 [CI, 1.07 to 3.15]). Treatment with misoprostol reduced the risk for serious gastrointestinal events by 40% (odds ratio, 0.60 [CI, 0.36 to 0.98]).