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Systematic reviews of the clinical effectiveness and cost-effectiveness of proton pump inhibitors in acute upper gastrointestinal bleeding: H. pylori eradication versus proton pump inhibitors |
Leontiadis G I, Sreedharan A, Dorward S, Barton P, Delaney B, Howden C W, Orhewere M, Gisbert J, Sharma V K, Rostom A, Moayyedi P, Forman D |
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CRD summary This review found no direct evidence to determine whether long-term aspirin or non-aspirin NSAID use prevented further upper gastrointestinal bleeding. There were no treatment differences between proton pump inhibitor and H. pylori eradication therapy in patients diagnosed with H. pylori infection. Given several limitations, including lack of validity assessment and potential for bias, the authors' conclusions may not be reliable. Authors' objectives To compare the effectiveness of Helicobacter pylori (H. pylori) eradication therapy with proton pump inhibitor maintenance therapy for the prevention of upper gastrointestinal bleeding in patients using non-steroidal anti-inflammatory drugs (NSAIDs). Searching MEDLINE (1966 to February 2006), EMBASE (1980 to February 2006) and The Cochrane Library were searched for articles in any language. Search terms were reported. Study selection Randomised controlled trials (RCTs) comparing H. pylori eradication therapy with proton pump inhibitor therapy or placebo in patients with H. pylori infection, diagnosed with peptic ulcer bleeding and taking NSAIDs were eligible for inclusion in the review. Studies of patients using concomitant therapy were only eligible if such therapy was administered equally to each treatment group. Eligible studies were required to use an intention-to-treat (ITT) analysis and report bleeding from peptic ulcer as the primary outcome. Secondary outcomes were defined in the review. Most studies were primary prophylaxis studies that compared eradication therapy (with combinations of bismuth, tetracycline, omeprazole, amoxicillin, clarithromycin and pantoprazole for one or two weeks) versus no eradication, placebo and/or proton pump inhibitor (omeprazole or pantoprazole). Primary prevention was defined as the prevention of a first upper gastrointestinal event in patients using NSAIDs. Secondary prevention was defined as prevention of recurrent upper gastrointestinal events in patients who had experienced a first upper gastrointestinal event. Concurrent therapy included naproxen or diclofenac. Most studies reported endoscopic ulcers between one and six months as the outcome measure and one study reported recurrent bleeding.
Two reviewers independently screened papers for relevance. It was unclear how discrepancies were resolved. Assessment of study quality The authors did not state that they assessed validity. Data extraction Data were extracted on primary and secondary prophylaxis to calculate relative risks with 95% confidence intervals (CIs). It was unclear how many reviewers extracted the data and how discrepancies were resolved. Methods of synthesis A fixed-effect model was used to pool relative risks according to comparator treatment and whether proton pump inhibitor therapy was used after eradication or not. Data were graphically presented as forest plots and in tables. Results of the review Seven RCTs (n=1,754) were included in the review. Sample sizes ranged between 69 and 660 patients.
No studies were identified that compared H. pylori eradication therapy with proton pump inhibitor therapy for the primary prevention of upper gastrointestinal bleeding in NSAID users. One study (n=400) reported similar results using H. pylori eradication or omeprazole for the secondary prevention of recurrent bleeding in patients with H. pylori and patients with a history of upper gastrointestinal bleeding and taking low-dose aspirin. Omeprazole was more effective than H. pylori eradication therapy in preventing recurrent bleeding in patients using non-aspirin NSAIDs such as naproxen.
Six studies (n=1,354) assessed primary or secondary prevention of endoscopic peptic ulcers and reported a greater treatment effect with H. pylori eradication therapy compared to placebo for primary prevention (relative risk 0.35, 95% CI: 0.20 to 0.61), but no significant difference compared to proton pump inhibitor therapy. Studies that assessed secondary prevention of peptic ulcers showed no significant differences between H. pylori therapy and proton pump inhibitor therapy. No evidence was available to enable comparison of H. pylori eradication therapy with placebo. Authors' conclusions There was no direct evidence to determine whether long-term aspirin or non-aspirin NSAID use prevented further upper gastrointestinal bleeding. There were no statistical differences in treatment benefit from proton pump inhibitor or H. pylori eradication therapy in patients positively diagnosed with H. pylori infection in the prevention of development of endoscopic peptic ulcers. CRD commentary The review question and supporting inclusion criteria were clear and appropriate. A relevant literature search was conducted. Articles in any language were eligible, which minimised the potential for language bias. No attempts were made to locate unpublished data and publication bias was not assessed, so relevant papers may have been missed. Validity assessment was not performed, which may have affected the reliability of the authors' conclusions. Details were not provided for the data extraction process and it was unclear how discrepancies were resolved for screening papers, which meant that it was possible that reviewer error or bias may have been introduced. Statistical heterogeneity was not assessed. As there may have been clinical heterogeneity among patients and methodological differences in terms of interventions and doses used, it may not have been appropriate to pool the results. Confidence intervals were wide and there were only two studies that assessed secondary prevention of peptic ulcers, which may have affected the reliability of the results. Although the authors acknowledged the paucity of direct evidence, given the concerns regarding data pooling, the lack of any validity assessment and the potential for bias, the authors' conclusions may not be reliable. Implications of the review for practice and research Practice: The authors did not state any implications for practice.
Research: The authors stated that large-scale RCTs were urgently required to assess the long-term effects of proton pump inhibitors and H. pylori eradication therapy in the primary and secondary prevention of upper gastrointestinal bleeds in patients on long-term NSAID therapy. Funding Funded by the Health Technology Assessment (HTA) Programme, project number 03/12/03. Bibliographic details Leontiadis G I, Sreedharan A, Dorward S, Barton P, Delaney B, Howden C W, Orhewere M, Gisbert J, Sharma V K, Rostom A, Moayyedi P, Forman D. Systematic reviews of the clinical effectiveness and cost-effectiveness of proton pump inhibitors in acute upper gastrointestinal bleeding: H. pylori eradication versus proton pump inhibitors. Health Technology Assessment 2007; 11(51): 139-144 Other publications of related interest Leontiadis GI, Sreedharan A, Dorward S, Barton P, Delaney B, Howden CW, Orhewere M, Gisbert J, Sharma VK, Rostom A, Moayyedi P & Forman D. Systematic reviews of the clinical effectiveness and cost-effectiveness of proton pump inhibitors in acute upper gastrointestinal bleeding. Health Technology Assessment 2007;11(51):1-145. Indexing Status Subject indexing assigned by NLM MeSH Acute Disease; Aged; Anti-Inflammatory Agents, Non-Steroidal /adverse effects /therapeutic use; Congresses as Topic; Cost-Benefit Analysis; Databases, Bibliographic; Duodenal Ulcer /complications; Endoscopy, Gastrointestinal; Gastrointestinal Hemorrhage /drug therapy /economics /prevention & Helicobacter Infections /drug therapy; Helicobacter pylori /drug effects; Histamine H2 Antagonists /therapeutic use /economics; Middle Aged; Peptic Ulcer Hemorrhage /drug therapy /economics /prevention & Proton Pump Inhibitors /therapeutic use /economics; Quality-Adjusted Life Years; Randomized Controlled Trials as Topic; Treatment Outcome; Upper Gastrointestinal Tract /drug effects; control; control AccessionNumber 12008106884 Date abstract record published 12/08/2009 Record Status This is a critical abstract of a systematic review that meets the criteria for inclusion on DARE. Each critical abstract contains a brief summary of the review methods, results and conclusions followed by a detailed critical assessment on the reliability of the review and the conclusions drawn. |
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