Comparative Efficacy of Vonoprazan and Proton Pump Inhibitors in Gastrointestinal Ulcer Healing and Post-ESD Bleeding Prevention

Introduction: Gastric and duodenal ulcers, including those induced by endoscopic submucosal dissection (ESD) remain clinically important due to risks of delayed bleeding and impaired healing. Proton pump inhibitors (PPIs) like lansoprazole are a standard treatment. It is affected by the CYP2C19 polymorphisms. Vonoprazan, a potassium-competitive acid blocker (P-CAB) achieves rapid and potent acid suppression independent of CYP2C19 metabolism, offering potential advantages in post-ESD ulcer management. Aim: The aim of this study is to compare efficacy and safety of vonoprazan and PPIs in the gastric ulcer healing and prevention of post-ESD bleeding. Methodology: A systematic review was conducted following PRISMA guidelines. PubMed and Google Scholar were searched (January 2015–June 2025) for randomized controlled trials (RCTs) and observational studies involving human subjects. Outcomes included ulcer healing rates, delayed bleeding, and safety events. Result: Across multiple trials, vonoprazan and PPIs showed comparable overall efficacy in promoting ulcer healing, with >90% achieving scar-stage healing within 8 weeks. No significant difference was found in delayed bleeding or perforation rates. Subgroup analyses revealed potential benefits of vonoprazan in antithrombotic therapy patients, where bleeding risk was significantly lower than with PPIs. Preventive hemostasis during follow-up endoscopy was also less common with vonoprazan. The safety results were similar, with most adverse events being mild gastrointestinal symptoms. Conclusion: Vonoprazan and PPIs are effective for post-ESD ulcer management. While both achieve comparable healing and safety, vonoprazan may be preferable in high-risk populations, particularly patients on antithrombotic therapy due to its stable and potent acid suppression.