Elsevier

The Lancet

Volume 359, Issue 9300, 5 January 2002, Pages 14-22
The Lancet

Articles
Role of Helicobacter pylori infection and non-steroidal anti-inflammatory drugs in peptic-ulcer disease: a meta-analysis

https://doi.org/10.1016/S0140-6736(02)07273-2Get rights and content

Summary

Background

The relation between H pylori infection and use of non-steroidal anti-inflammatory drugs (NSAIDs) in the pathogenesis of peptic-ulcer disease is controversial. We undertook a meta-analysis to address this issue.

Methods

By computer and manually we sought observational studies on the prevalence of peptic-ulcer disease in adult NSAID takers or the prevalence of H pylori infection and NSAID use in patients with peptic-ulcer bleeding. Summary odds ratios were calculated from the raw data. Tests for homogeneity were done.

Findings

Of 463 citations identified, 25 studies met inclusion criteria. In 16 studies of 1625 NSAID takers, uncomplicated peptic-ulcer disease was significantly more common in patients positive than in those negative for H pylori (341/817 [41·7%] vs 209/808 [25·9%]; odds ratio 2·12 [95% CI 1·68–2·67]). In five controlled studies, peptic-ulcer disease was significantly more common in NSAID takers (138/385 [35·8%]) than in controls (23/276 [8·3%]), irrespective of H pylori infection. Compared with H pylori negative individuals not taking NSAIDs, the risk of ulcer in H pylori infected NSAID takers was 61·1 (9·98–373). H pylori infection increased the risk of peptic-ulcer disease in NSAID takers 3·53-fold in addition to the risk associated with NSAID use (odds ratio 19·4). Similarly, in the presence of risk of peptic-ulcer disease associated with H pylori infection (18·1), use of NSAIDs increased the risk of peptic-ulcer disease 3·55-fold. H pylori infection and NSAID use increased the risk of ulcer bleeding 1·79-fold and 4·85-fold, respectively. However, the risk of ulcer bleeding increased to 6·13 when both factors were present.

Interpretation

Both H pylori infection and NSAID use independently and significantly increase the risk of peptic ulcer and ulcer bleeding. There is synergism for the development of peptic ulcer and ulcer bleeding between Hpylori infection and NSAID use. Peptic-ulcer disease is rare in H pylori negative non-NSAID takers.

Introduction

The relation between infection with Helicobacter pylori and use of non-steroidal anti-inflammatory drugs (NSAIDs) in the pathogenesis of peptic-ulcer disease is controversial, because studies examining these two risk factors in this disorder have had conflicting results.1, 2, 3, 4 From conventional thinking, the presence of both these well-established risk factors for peptic-ulcer disease would be expected to increase the risk of the disease. However, this was not the case in several observational studies of patients taking NSAIDs, in which peptic-ulcer disease was less frequently diagnosed when H pylori infection was present than in patients without the infection.5, 6 Conflicting results have also been reported from randomised controlled clinical trials on whether eradication of H pylori infection retards ulcer healing7, 8 or reduces the risk of developing peptic-ulcer disease in NSAID takers.9, 10

The discrepancies probably reflect a complex relation between H pylori infection and NSAID-associated gastropathy as well as methodological heterogeneity between studies. For example, study populations have differed in terms of NSAID exposure, the controls used for comparison, and the definition of ulcer size.11, 12, 13, 14, 15, 16, 17, 18 Therefore, there are four possible situations for H pylori infection and NSAID-associated gastropathy: no interaction, or additive, synergistic, or antagonistic effects between the two risk factors. The aims of this analysis were to review systematically the literature on the relation between H pylori infection and NSAID-associated gastropathy; to assess the presence and magnitude of any possible interaction on peptic-ulcer disease between these two risk factors; to examine any possible interaction between the two risk factors with respect to the site of ulcer or ulcer bleeding; and to explore any sources of heterogeneity between the published studies.

Section snippets

Design and procedures

A computerised literature search was done in the MEDLINE, PubMed, and Cochrane databases for relevant systematic reviews published in any language between 1984 and October 2000, with the following MeSH terms and/or textwords: meta-analysis, systematic review, overview, NSAIDs, and pylori. 15 potentially relevant citations were identified. By previously described criteria19, 20 and guidelines for the application of meta-analysis in epidemiological studies,21 these reports were examined

Publications

The literature search in the three databases generated 463 citations, and screening of citation titles and abstracts identified 61 potentially relevant studies for full article retrieval. Of these, 36 studies were subsequently excluded: H pylori eradication study;8, 9, 10 treatment trial with omeprazole or H2-receptor antagonists or misoprostol;27, 28, 29 no baseline endoscopy data;30 no raw data on peptic-ulcer disease or H pylori status;31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44,

Discussion

Previous studies have shown that H pylori infection or use of NSAIDs confers a three-fold to four-fold increased risk of peptic-ulcer disease.74, 75, 76 However, whether the magnitude of the risk reported in these studies was for the individual or combined contribution of H pylori infection and NSAIDs to the development of peptic-ulcer disease or ulcer complications was not known.

We have found, in this systematic review, that a third of patients taking NSAIDs long term had gastric or duodenal

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