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.