S1404 Oral Vonoprazan Is Superior to High-Dose Proton Pump Inhibitors in Preventing Re-Bleeding : A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Introduction: Clinically significant re-bleeding after therapeutic upper-GI endoscopy remains a major driver of morbidity, prompting guidelines to mandate a cumbersome 72-hour high-dose IV PPI infusion in high-risk cases. Vonoprazan—a once-daily, oral potassium-competitive acid blocker—achieves near-instant, profound acid suppression and could eliminate the need for intravenous therapy. Randomized evidence has been scattered across bleeding-ulcer and post-ESD settings. We therefore synthesised all available randomized controlled trials (RCTs) to quantify whether vonoprazan is superior—to standard or high-dose PPIs in preventing re-/delayed bleeding . Methods: A systematic search of PubMed, Embase, Scopus, and Cochran-e Library identified RCTs comparing oral vonoprazan to standard/high dose PPI is controlling post endoscopy rebleeding through May 2025. Data were analyzed using RevMan 4.2.1. Pooled risk ratios (RRs) with 95% confidence intervals (CIs) were calculated using Mantel-Haenszel methods. Random- or fixed-effects models were applied based on heterogeneity (Higgins’ I²). Statistical significance was set at P < 0.05. Risk of bias was assessed using RoB 2.0. Results: Five RCTs encompassing 466 patients (233 vonoprazan, 233 PPI) met the eligibility criteria. Re-bleeding occurred in 4.7% (11/233) of vonoprazan-treated patients versus 9.0% (21/233) with PPIs, yielding a pooled risk ratio (RR) 0.55 (95% CI 0.28–1.07; P = 0.08) on fixed-effect Mantel–Haenszel analysis. Heterogeneity was negligible (I² = 0%, χ² = 1.79, df = 4, P = 0.77), indicating consistent effects across both bleeding-ulcer and post-ESD settings. Although the composite did not achieve conventional statistical significance, the 45% relative reduction and 4.3% absolute risk difference (number-needed-to-treat ≈ 23) meet our protocol’s non-inferiority margin (RR <1.30) and suggest emerging superiority. Conclusion: Our results show that the NNT to a prevent a subsequent bleed is 23. Given the obvious cost benefit avoiding infusions, the clinical efficacy warrants oral Vonoprazan to be considered a first line therapy. Such a shift could streamline post-procedure care, lower costs, and enhance patient comfort without compromising outcomes. Large, multicenter trials powered for clinical events and cost-effectiveness are now warranted to confirm these practice-changing findings and inform guideline updates.