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Interaction Between NSAIDs and H. pylori in Peptic Ulcer Disease

The interaction between Helicobacter pylori infection and use of nonsteroidal anti-inflammatory drugs is controversial. The results of this meta-analysis add significantly to the confusion about the potential interaction between H. pylori and NSAID use in peptic ulcer disease.

Helicobacter pylori infection and the use of nonsteroidal anti-inflammatory drugs (NSAIDs) are the most common causes of peptic ulcer disease. The interaction between these risk factors, however, is controversial: Some study results suggest a strong synergistic effect that increases the risk for ulcers, whereas other results suggest that H. pylori infection protects against formation of NSAID-associated ulcers.

To address this controversy, investigators searched MEDLINE, PubMed, and Cochrane databases to identify observational studies that reported independent event rates for peptic ulcer disease and ulcer bleeding in patients taking NSAIDs, in patients with H. pylori infection, or in patients with both risk factors. Manual searches for relevant articles also were performed, but European and Asian databases were not searched, and abstracts were not included. Papers were rated for quality and were excluded by explicit criteria.

Separate odds ratios for developing any ulcer, gastric ulcer, duodenal ulcer, or bleeding ulcer were calculated using data from 25 studies that met inclusion criteria. Significant heterogeneity suggested that the data were too diverse to combine, and multiple sensitivity analyses were performed to explain the differences among studies. NSAID use and H. pylori infection each independently increased risk for peptic ulcers and ulcer bleeding. When both risk factors were present, there was a significant interaction that further increased risk for ulcers or bleeding beyond the additive effect of each risk factor.

Comment: The results of this meta-analysis add significantly to the confusion about the potential interaction between H. pylori and NSAID use in peptic ulcer disease. The suggestion of a strong synergistic effect between the 2 risk factors contradicts results of larger cohort and case-control studies. Because the primary analyses demonstrated heterogeneity of results, I wonder whether, in this case, an individual large trial provides more meaningful results than meta-analysis of multiple smaller trials. For example, in a large randomized controlled trial (involving more than 8000 patients), investigators examined rates of symptomatic and complicated ulcers in rheumatoid arthritis patients taking rofecoxib or naproxen; their study showed a much smaller, but statistically significant, increased risk for ulcers in patients with H. pylori infection than in NSAID users without H. pylori infection (JW Gastro Jan 2001, p. 1, accession number 001212001, and N Engl J Med 2000; 343:1520). These results were not included in the meta-analysis, presumably because some patients took anticoagulants or corticosteroids. In any event, methodologic limitations and heterogeneity of data prevent the meta-analysis from providing compelling evidence to suggest any change in the clinical approach to H. pylori-infected patients who are taking NSAIDs.

— David J. Bjorkman, MD, MSPH, SM (Epid.)

Published in Journal Watch Gastroenterology February 13, 2002

Citation(s):

Huang JQ.Role of Helicobacter pylori infection and non-steroidal anti-inflammatory drugs in peptic-ulcer disease: A meta-analysis.Lancet 2002 Jan 5; 359:14-22.

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