Proton Pump Inhibitor Therapy for Peptic Ulcer Bleeding: Cochrane Collaboration Meta-analysis of Randomized Controlled Trials
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OBJECTIVE: To evaluate the efficacy of proton pump inhibitors (PPIs) in treating peptic ulcer bleeding. MATERIAL AND METHODS: We searched the MEDLINE, EMBASE, CENTRAL, Cochrane Library, and metaRegister of Controlled Trials databases and published proceedings of major meetings through November 2004 for randomized controlled trials that compared oral or intravenous PPIs with placebo or a histamine2-receptor antagonist for peptic ulcer bleeding. Pharmaceutical companies and relevant experts were contacted. Data extraction and assessment of study validity were performed independently in duplicate. Assessed outcomes were 30-day all-cause mortality, rebleeding, surgery, and repeated endoscopic treatment. Influence of study characteristics on outcomes was examined by subgroup analyses and meta-regression. RESULTS: We included 24 trials (4373 participants). Statistical heterogeneity was evident only for rebleeding. Treatment with PPIs had no significant effect on mortality (odds ratio [OR], 1.01; 95% confidence interval [CI], 0.74-1.40; number needed to treat [NNT], incalculable) but significantly reduced rebleeding (OR, 0.49; 95% CI, 0.37-0.65; NNT, 13) and the need for surgery (OR, 0.61; 95% CI, 0.48-0.78; NNT, 34) and repeated endoscopic treatment (OR, 0.32; 95% CI, 0.20-0.51; NNT, 10). Results were similar when analysis was confined to trials with adequate allocation concealment. Treatment with PPIs significantly reduced mortality in Asian trials (OR, 0.35; 95% CI, 0.16-0.74; NNT, 34) and in patients with active bleeding or a nonbleeding visible vessel (OR, 0.53; 95% CI, 0.31-0.91; NNT, 50). CONCLUSIONS: In ulcer bleeding, PPIs reduce rebleeding and the need for surgery and repeated endoscopic treatment. They improve mortality among patients at highest risk.