The effectiveness of vonoprazan relative to that of proton pump inhibitors (PPIs) after gastric endoscopic submucosal dissection (ESD) is unclear. Although previous studies used post-ESD ulcer healing as the outcome measure, post-ESD bleeding rate is the most objective and appropriate outcome measure as it has less ascertainment bias. We aimed to compare the post-ESD bleeding rates between vonoprazan and PPIs.

This nationwide population-based retrospective cohort study was conducted between 2014 and 2018 and involved nine hospitals. After 2 days of intravenous PPI administration, either vonoprazan or PPI was administrated from postoperative day 2 to day 30.

Overall, data of 1,715 patients (627 patient pairs) were analyzed through propensity score matching. The vonoprazan group had significantly lower post-ESD bleeding rates than the PPI group (overall: 11.9% vs 17.2%, P=0.008; bleeding between days 2 and 30: 7.8% vs 11.8%, P=0.015). The readmission rate due to post-ESD bleeding was lower in the vonoprazan group (2.4% vs 4.1%, P=0.081). Blood transfusion (2.1% vs 3.0%, P=0.15) and additional surgery due to delayed perforation (0.5 vs 1.0%, P=0.32) were not significantly different between the 2 groups. No deaths within 30 days occurred in both groups. On Cox regression analysis, vonoprazan use, lesion location (antrum), aspirin use, direct oral anticoagulant use, and Charlson Comorbidity Index (≥2) were associated with an increased risk of post-ESD bleeding within 30 days.

Vonoprazan has a lower post-ESD bleeding rate than PPIs. Further prospective studies are required to confirm these results.