Potassium-competitive acid channel blockers versus Proton-Pump inhibitors in the prevention of post-endoscopic peptic ulcer rebleeding: A systematic review and meta-analysis

ABSTRACT Introduction Vonoprazan, a new oral potassium-competitive acid blocker (PCAB), has shown promise in terms of superior acid suppression when compared to Proton-pump inhibitors (PPIs). We evaluated the efficacy of PCABs versus PPIs in preventing rebleeding in high-risk peptic ulcer patients after endoscopic hemostasis. Methods Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we conducted a comprehensive search for relevant studies across Medline, Embase, Web of Science, Cochrane Central Register of Controlled Trials and ClinicalTrials.gov , from inception till March 25, 2025. The primary outcome of interest was peptic ulcer rebleeding rate. Pooled risk ratios (RR) and mean difference (MD) with the corresponding 95% confidence intervals (CIs) were calculated. Results Three studies with 54,410 patients receiving endoscopic hemostasis for peptic ulcer bleeding were included in our analysis. The mean age of included participants was 71 ± 1.83 years. There was no significant difference in rebleeding rates between patients receiving PPIs and PCABs (RR 0.827; 95 % CI: 0.5 –1.3). We observed a significant reduction in length of hospital stay in the PCAB group when compared to the PPI group (MD: -0.44, 95% CI: -0.72 - -0.17), but no significant difference in all-cause mortality between both groups (RR: 0.90, 95% CI: 0.79 - 1.04). Conclusions Our study demonstrates comparable efficacy of PPIs and PCABs in preventing rebleeding in patients with high-risk peptic ulcers after successful endoscopic hemostasis. However, there was a significant reduction in hospital length of stay favoring PCABs. Research in Context What is already known on this topic Bleeding from peptic ulcers is considered one of the major reasons for mortality and hospitalization, and the standard treatment after endoscopic hemostasis is the administration of high-dose proton pump inhibitors (PPIs). Potassium competitive acid blockers (PCABs), such as vonoprazan, have been reported to have more potent and faster onset of action than PPIs in the treatment of acid-related diseases, but their efficacy in the prevention of post-endoscopic peptic ulcer rebleeding has not been well established in the literature in the form of a dedicated meta-analysis. What this study adds In the present study, the efficacy and safety of PCABs in the prevention of post-endoscopic rebleeding and mortality in 54,410 patients with high-risk peptic ulcer bleeding were investigated in the context of a systematic review and meta-analysis. PCABs were found to have similar efficacy to PPIs in the prevention of mortality and rebleeding in the context of endoscopic hemostasis, and the use of PCABs was also observed to reduce the length of stay in the hospital to a significant extent. How this study might affect research, practice or policy These findings indicate that PCABs are a reasonable alternative to PPIs in post-endoscopic management of high-risk peptic ulcer bleeding and may be particularly useful in situations where early discharge and optimization of resources are critical. Additional large-scale studies in different populations are required to validate these findings and create guidelines