Use of proton pump inhibitors

What is already known on this topic

- Previous observational studies and meta-analyses suggest that exposure to proton-pump inhibitors (PPIs) is associated with increased risk of gastric cancer .

- Several methodological issues and biases may affect this area of research.

- The causal role of PPI use on the development of gastric cancer is still heavily debated in the medical community.

What we did

- Systematic search of Medline/PubMed, Embase and Scopus databases for randomized and observational studies of the association between PPIs and gastric cancer

having considered Histamine-2 receptor antagonists (H2RAs) users as controls

- Stratified analyses and meta-regression were employed to explore heterogeneity.

- We used GRADE to evaluate certainty in the body of evidence.

- 2 randomized clinical trials (498 patients; 1 gastric cancer)

- 12 Observational studies (>6 million patients; 11,554 gastric cancers)

➢ 6 studies provided a comprehensive adjustment of confounding

➢ 3 studies provided partially-adjusted effect estimate

➢ 2 studies provided crude/unadjusted relative risk estimate

➢ 1 study excluded due to population overlap

The 6 observational studies providing comprehensive adjustment of confounding

included about 2.5 million patients receiving either PPIs or H2RAs and 7,372 gastric cancers

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