Long-term use of potassium-competitive acid blockers and proton pump inhibitors and the risk of metachronous gastric cancer after H. pylori eradication: a multicenter cohort study.

BACKGROUND AND AIMS: Gastric cancer remains a significant health burden, especially in Asia. Potassium-competitive acid blockers (P-CABs) provide stronger acid suppression than proton pump inhibitors (PPIs), but their long-term impact on metachronous gastric cancer (MGC) remains unclear. This study evaluated the incidence and duration-dependent risk of MGC in P-CAB/PPI users. METHODS: This multicenter retrospective cohort study included patients from 15 institutions in Japan who underwent endoscopic or surgical resection for gastric cancer between 2014 and 2022. After exclusions, 7172 patients who had received H. pylori eradication were analyzed. Chronic use of P-CAB/PPI was defined as administration for more than 3 months. The primary outcome was the incidence of MGC. Cox regression models were used, along with subgroup analyses based on duration and initial treatment type (endoscopy versus surgery). RESULTS: During a median follow-up of 5.8 years, MGC developed in 342 patients. The incidence was highest among P-CAB users (20.9 per 1,000 person-years), followed by PPI users (13.5) and non-users (7.1). Both P-CAB and PPI use were independently associated with increased MGC risk (hazard ratio 3.89 and 1.75, respectively). The association between P-CAB use and MGC was stronger with longer durations of use (hazard ratio 3.44 for < 1 year, 3.95 for 1–3 years, and 9.36 for > 3 years) and was particularly evident in the post-endoscopic group (hazard ratio 4.22) in subgroup analyses. CONCLUSIONS: Chronic use of P-CAB/PPI were associated with MGC. Longer duration may be associated with increased risk of MGC. Further studies are warranted to validate these findings.