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Proton pump inhibitor use associated with an increased risk of gastric cancer
Clinical Question
Is there an association between gastric cancer and the use of proton pump inhibitors?
Bottom line
This is the strongest evidence to date that there is a small but clinically significant increase in the risk of gastric cancer for patients taking a PPI (number needed to treat to harm = 1191 over 10 years). Physicians initiating anti-acid therapy for patients should begin with an H2RA, and if prescribing a PPI, should use the lowest dose and duration possible. Another recent study in the same journal using data from a Korean registry produced similar findings (Gut 2021;70:2066-2075 doi:10.1136/gutjnl-2020-323845).
This POEM aligns with the Choosing Wisely Canada recommendation that advises not to maintain long-term PPI therapy for gastrointestinal symptoms without stopping at least once per year in most patients. Choosing Wisely Canada’s toolkit provides tools for deprescribing PPIs.
2b
Reference
Study design: Cohort (retrospective)
Funding: Government
Setting: Population-based
Synopsis
Proton pump inhibitors (PPIs) cause hypergastrinemia, which can lead to hyperplasia of the gastric mucosa, and several previous studies have shown an association between PPI use and gastric cancer. This study is the largest and most methodologically sound; it addresses several potential sources of confounding better than previous studies. The authors identified more than 1.1 million persons who had received a new prescription for a PPI between 1990 and 2018, and another 220,825 persons who had received a new prescription for a histamine-2 receptor antagonist (H2RA) during the same period. This is a better comparison group than the general population, since it avoids confounding by indication (PPI users may have different risk factors and health habits than non-users). Persons with a familial syndrome associated with gastric cancer, persons with previous gastric cancer, and those who had less than one year of follow-up were excluded, leaving 973,281 PPI patients and 198,306 H2RA patients. The authors matched patients using propensity scores that incorporated a large array of potential confounders, including age, comorbidities, tobacco and alcohol use, and medications. In the fully adjusted model, the authors found a significantly increased risk of gastric cancer in PPI users compared with H2RA users (hazard ratio [HR] = 1.45; 95% CI 1.06 - 1.98; number needed to treat to harm = 2121 after 5 years and 1191 after 10 years). The Kaplan-Meier survival analysis showed that the risk increased linearly with the duration of PPI use. Greater doses were associated with increased risk: HR = 1.22 for less than 14,600 mg cumulative omeprazole dose equivalents; HR = 1.81 for 14,600 mg to 28,199 mg dose equivalents; and HR = 2.03 for 29,200 mg and higher dose equivalents (although the confidence intervals overlap).
Reviewer
Mark H. Ebell, MD, MS
Professor
University of Georgia
Athens, GA
Comments
There’s no point of this article
There’s no point of this article
ppi use
major concern
chronic ppi rx
? possibly minimal increase in gastric ca over 10 yrs