Vonoprazan vs proton pump inhibitors in treating post-endoscopic submucosal dissection ulcers and preventing bleeding: A meta-analysis of randomized controlled trials and observational studies.

Background: Vonoprazan is a potassium-competitive acid blocker (P-CAB) that is frequently used in Japan for Helicobacter pylori (H. pylori) eradication, treatment of gastroesophageal reflux disease, and treatment of post endoscopic submucosal dissection (ESD) complications. We sought to determine if vonoprazan was superior to proton pump inhibitors (PPIs) for treating ESD-induced ulcers (as assessed by ulcer healing and shrinkage ratios) and preventing delayed bleeding over various treatment durations (2, 4, and 8 weeks).

Methods: We collected randomized controlled trials (RCTs) and observational studies that discussed the effectiveness of vonoprazan and PPIs on ESD-induced ulcers and bleeding from PubMed, Cochrane Library, ClinicalTrials.gov, and Google Scholar. Studies were selected according to pre-established eligibility criteria and data were extracted separately by 2 researchers with double-check. We used the Cochrane risk of bias tool to assess RCTs and the Newcastle-Ottawa Quality Assessment Scale to assess observational studies. Meta-analyses, based on the random-effects model, were conducted to compare differences in ulcer shrinkage ratios (%) and odds ratios (ORs) for ulcer healing and delayed bleeding. Publication bias was evaluated using funnel plots and Egger regression test. Heterogeneity was assessed using I statistics. A sensitivity analysis was conducted to check the robustness of results. The evidential quality of the findings was assessed using the GRADE profiler.

Results: Thirteen studies were included in this meta-analysis. The OR effect sizes of vonoprazan relative to PPIs for ulcer healing were 1.33 (P = .13) with a 95% CI (0.33-3.21) at 4 weeks and 1.48 (P = .09) with a 95% CI (0.81-5.20) at 8 weeks. The overall effect size for the shrinkage ratio was 12.24% (P = .16) with a 95% CI (-4.96-29.44) at 2 weeks. The effect size of its subgroup of H. pylori-positive patients was 19.51% (P < .001) with a 95% CI (11.91-27.12). The overall OR for the occurrence of delayed bleeding was 0.66 (P = .26) with a 95% CI (0.32-1.35). After excluding combination drug studies, the overall ORs between vonoprazan and PPIs on ulcer healing and delayed bleeding were 1.44 and 0.76, respectively.

Conclusion: During the first 2 weeks of treatment, vonoprazan was more effective than PPIs for treating H. pylori-positive patients with ESD-induced gastric ulcers.