Krishnan A, Schneider CV, Walsh D. Proton pump inhibitors and all-cause mortality risk among cancer patients. World J Clin Oncol 2025; 16(1): 99240 [DOI: 10.5306/wjco.v16.i1.99240]
Corresponding Author of This Article
Arunkumar Krishnan, MD, MS, Assistant Professor, Research Scientist, Department of Supportive Oncology, Atrium Health Levine Cancer, 1021 Morehead Medical Drive, Suite 70100, Charlotte, NC 28204, United States. dr.arunkumar.krishnan@gmail.com
Research Domain of This Article
Gastroenterology & Hepatology
Article-Type of This Article
Retrospective Study
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
World J Clin Oncol. Jan 24, 2025; 16(1): 99240 Published online Jan 24, 2025. doi: 10.5306/wjco.v16.i1.99240
Proton pump inhibitors and all-cause mortality risk among cancer patients
Arunkumar Krishnan, Carolin Victoria Schneider, Declan Walsh
Arunkumar Krishnan, Declan Walsh, Department of Supportive Oncology, Atrium Health Levine Cancer, Charlotte, NC 28204, United States
Arunkumar Krishnan, Department of Medicine, Section of Hematology and Oncology, Wake Forest University School of Medicine, Winston-Salem, NC 27101, United States
Carolin Victoria Schneider, Department of Medicine III, Gastroenterology, Metabolic Diseases, and Intensive Care, University Hospital RWTH Aachen, Aachen 52074, Germany
Author contributions: Krishnan A contributed to the concept of the study and study design and was responsible for data acquisition and statistical analysis; Krishnan A and Schneider CV drafted the manuscript; Walsh D participated in the review and editing. All authors were involved with interpreting the data and critically revising the manuscript for important intellectual content. All authors reviewed and approved the final version of the manuscript.
Institutional review board statement: TriNetX data have been granted a waiver from the Western institutional review board as a federated network as only aggregated counts and statistical summaries of de-identified information were included.
Informed consent statement: Not applicable for de-identified data.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Arunkumar Krishnan, MD, MS, Assistant Professor, Research Scientist, Department of Supportive Oncology, Atrium Health Levine Cancer, 1021 Morehead Medical Drive, Suite 70100, Charlotte, NC 28204, United States. dr.arunkumar.krishnan@gmail.com
Received: July 17, 2024 Revised: September 9, 2024 Accepted: October 11, 2024 Published online: January 24, 2025 Processing time: 104 Days and 17.1 Hours
Abstract
BACKGROUND
Proton pump inhibitors (PPIs) are widely used, including among cancer patients, to manage gastroesophageal reflux and other gastric acid-related disorders. Recent evidence suggests associations between long-term PPI use and higher risks for various adverse health outcomes, including greater mortality.
AIM
To investigate the association between PPI use and all-cause mortality among cancer patients by a comprehensive analysis after adjustment for various confounders and a robust methodological approach to minimize bias.
METHODS
This retrospective cohort study used data from the TriNetX research network, with electronic health records from multiple healthcare organizations. The study employed a new-user, active comparator design, which compared newly treated PPI users with non-users and newly treated histamine2 receptor antagonists (H2RA) users among adult cancer patients. Newly prescribed PPIs (esomeprazole, lansoprazole, omeprazole, pantoprazole, or rabeprazole) users were compared to non-users or newly prescribed H2RAs (cimetidine, famotidine, nizatidine, or ranitidine) users. The primary outcome was all-cause mortality. Each patient in the main group was matched to a patient in the control group using 1:1 propensity score matching to reduce confounding effects. Multivariable Cox regression models were used to estimate hazard ratios (HRs) and 95% confidence interval (CI).
RESULTS
During the follow-up period (median 5.4 ± 1.8 years for PPI users and 6.5 ± 1.0 years for non-users), PPI users demonstrated a higher all-cause mortality rate than non-users after 1 year, 2 years, and at the end of follow up (HRs: 2.34-2.72). Compared with H2RA users, PPI users demonstrated a higher rate of all-cause mortality HR: 1.51 (95%CI: 1.41-1.69). Similar results were observed across sensitivity analyses by excluding deaths from the first 9 months and 1-year post-exposure, confirming the robustness of these findings. In a sensitivity analysis, we analyzed all-cause mortality outcomes between former PPI users and individuals who have never used PPIs, providing insights into the long-term effects of past PPI use. In addition, at 1-year follow-up, the analysis revealed a significant difference in mortality rates between former PPI users and non-users (HR: 1.84; 95%CI: 1.82-1.96).
CONCLUSION
PPI use among cancer patients was associated with a higher risk of all-cause mortality compared to non-users or H2RA users. These findings emphasize the need for cautious use of PPIs in cancer patients and suggest that alternative treatments should be considered when clinically feasible. However, further studies are needed to corroborate our findings, given the significant adverse outcomes in cancer patients.
Core Tip: Proton pump inhibitors (PPIs) are commonly used medications. Recent studies have raised concerns regarding increased all-cause and cause-specific mortality with PPIs. However, limited studies have addressed this issue in cancer patients. In addition, an association between PPIs and the mortality risk in unselected cancer populations remains uncertain. We investigated the association between PPI use and all-cause mortality in patients diagnosed with cancer. PPI use among cancer patients was associated with a higher risk of all-cause mortality compared to non-users or histamine-2 receptor antagonist users. These results strongly suggest the need for cautious use of PPIs in cancer patients and indicate that alternative treatments should be considered when clinically feasible.
