ORIGINAL ARTICLE
Proton Pump Inhibitor Therapy for Peptic Ulcer Bleeding: Cochrane Collaboration Meta-analysis of Randomized Controlled Trials

https://doi.org/10.4065/82.3.286Get rights and content

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.

Section snippets

MATERIAL AND METHODS

We included trials that compared intravenous or oral PPIs with placebo or a histamine2-receptor antagonist (H2RA) in patients with ulcer bleeding. All trials had to confirm endoscopically the diagnosis of active or recent bleeding from peptic ulcer, use a concurrent control group, apply concomitant therapy equally to both intervention arms, and report 1 or more of the following: mortality, rebleeding, and surgical intervention.

Our primary outcome measure was mortality from any cause within 30

RESULTS

Our initial search identified 181 articles; reference lists from these articles and conference proceedings identified an additional 16 articles (Figure 1). We identified no additional trials by searching online registers of controlled trials or by contacting experts in the field or pharmaceutical companies that market PPIs. After reviewing the abstracts of these articles, we excluded 143 as irrelevant and retrieved the full text for the remaining 54. Of these, 30 did not meet eligibility

DISCUSSION

These results extend and update our previous analyses.1, 2 Treatment with PPIs consistently reduces the rate of rebleeding after an episode of ulcer bleeding and also reduces the requirement for surgical treatment. New findings that add to existing knowledge are that PPI treatment reduces all-cause mortality among patients with major endoscopic stigmas and reduces the requirement for repeated endoscopic hemostatic treatment. Trials conducted in Asia demonstrate some important differences in

CONCLUSIONS

Treatment with PPIs plays an important part in the management of patients with ulcer bleeding. It reduces rebleeding and the requirements for surgical intervention and additional endoscopic hemostatic treatment. When appropriately combined with endoscopic hemostatic treatment, PPI treatment also improves mortality among patients with the highest-risk endoscopic findings.

Acknowledgments

We thank Iris Gordon, MSc, trial search coordinator, Cochrane Collaboration, Upper Gastrointestinal and Pancreatic Diseases Group, University of Leeds, for her help with the literature search.

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    Data were presented in part at the 106th Annual Meeting of the American Gastroenterological Association, Chicago, Ill, May 18, 2005, and have been published in abstract form (Leontiadis et al. Gastroenterology. 2005; 128[suppl 2]:A-639. Abstract W1568). This report is based on a review3 published online in The Cochrane Library (www.thecochranelibrary.com), which will be updated regularly.

    1

    Dr Leontiadis receives grants to attend meetings from AstraZeneca Pharmaceuticals LP, Janssen-Cilag, GlaxoSmithKline, and Sanofi-Aventis. Dr Sharma receives speaking honoraria and research support from TAP Pharmaceutical Products Inc and is a consultant for Astra-Zeneca Pharmaceuticals LP. Dr Howden is a consultant for TAP Pharmaceutical Products Inc, Altana, Santarus, Inc, Schwarz Pharma, NEGMA-GILD, Allergan Inc, Novartis Consumer Health, Takeda Pharmaceuticals America, Inc, and Valeant Pharmaceuticals International; receives speaking honoraria from TAP Pharmaceutical Products Inc, Santarus, Inc, Takeda (Japan), Takeda (Austria), Abbott (Canada), Wyeth (US), Wyeth (Ireland), NEGMA-GILD, and AstraZeneca Pharmaceuticals LP, and receives research support from AstraZeneca Pharmaceuticals LP.

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    Copyright © 2007 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.