Use of Acid-Suppressant Medications After Diagnosis Increases Mortality in a Subset of Gastrointestinal Cancer Patients

Abstract

Background

Acid-suppressant medications, including proton pump inhibitors (PPIs) and H2 receptor antagonists (H2RAs), are frequently prescribed and have been linked to increased risk of some gastrointestinal cancers.

Aims

We examined whether post-diagnosis use of PPIs/H2RAs is associated with the risk of mortality in gastrointestinal cancer patients.

Methods

We used data from patients with esophageal cancer, gastric cancer, or hepatocellular carcinomas (HCCs) in the national VA Central Cancer Registry diagnosed between 2002 and 2016. We identified PPI/H2RA prescriptions that were filled before and after cancer diagnosis and used time-dependent Cox regression models to calculate adjusted hazard ratios (HRs) and 95% CIs for mortality risk. We used a time-varying exposure to avoid immortal-time bias and a 3-month lag to reduce reverse causation. A sensitivity analysis was conducted varying the lag duration between the date of cancer diagnosis and the start of follow-up.

Results

PPIs were used by the majority (54% post-diagnosis use) of patients. We found no association between post-diagnosis PPI use and cancer-specific mortality in esophageal adenocarcinoma (HR 0.93; 95% CI 0.84–1.02), esophageal squamous cell carcinoma (HR 0.99; 95% CI 0.87–1.12), or gastric cardia cancer (HR 1.04; 95% CI 0.89–1.22) patients. Post-diagnosis PPI use was, however, associated with the increased risk of cancer-specific mortality for patients with gastric non-cardia cancer (HR 1.50; 95% CI 1.29–1.74) and HCC (HR 1.31; 95% CI 1.23–1.40). The results were similar for associations with post-diagnosis use of H2RAs. There was no association with pre-diagnosis PPI/H2RA use.

Conclusion

Post-diagnosis PPI/H2RA use was associated with the increased mortality in gastric non-cardia cancer and HCC patients.

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Funding

This work was supported in part by National Institutes of Health grant P30 DK056338 (Study Design and Clinical Research Core), which supports the Texas Medical Center Digestive Diseases Center. This research was supported in part with resources at the VA HSR&D Center for Innovations in Quality, Effectiveness and Safety (#CIN 13-413), at the Michael E. DeBakey VA Medical Center, Houston, TX. The opinions expressed reflect those of the authors and not necessarily those of the Department of Veterans Affairs, the United States government or Baylor College of Medicine.

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APT was involved in study concept and design. APT and YL performed statistical analysis and interpretation of data. HES and APT were involved in acquisition of data and obtained funding. YL prepared the data. SA, MCT, HES, and APT drafted the manuscript. SA, MCT, YL, HES, and APT were involved in critical review of the manuscript for important intellectual content. All authors read and approved the final version for submission.

Corresponding author

Correspondence to Aaron P. Thrift.

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Cite this article

Ayyagari, S., Tan, M.C., Liu, Y. et al. Use of Acid-Suppressant Medications After Diagnosis Increases Mortality in a Subset of Gastrointestinal Cancer Patients. Dig Dis Sci 65, 2691–2699 (2020). https://doi.org/10.1007/s10620-019-05984-x

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Keywords

  • Cancer
  • Mortality
  • Prognosis
  • Acid-suppressant medication use