S1422 Oral Vonoprazan Is Noninferior to Intravenous Proton Pump Inhibitors for Peptic Ulcer Rebleeding: A Matched Cohort Analysis of Clinical Outcomes

Introduction: The American College of Gastroenterology (ACG) guidelines recommend high-dose intravenous proton pump inhibitor (PPI) therapy for 72 hours following successful endoscopic hemostasis of peptic ulcer bleeding. Vonoprazan, a novel potassium-competitive acid blocker (PCAB), is gaining use in acid-related gastrointestinal disorders. This study aimed to compare the efficacy of oral vonoprazan versus intravenous PPIs in preventing peptic ulcer rebleeding using a real-world national database. Methods: We conducted a retrospective cohort study using the TriNetX research network to identify hospitalized adults (≥18 years) with peptic ulcer bleeding treated with oral vonoprazan or intravenous PPIs. Patients were matched 1:1 using propensity scores based on demographics, race/ethnicity, comorbidities, and medication use. The primary outcome was 30-day ulcer rebleeding. Secondary outcomes included readmission rates, emergency department visits, blood transfusion, all-cause mortality, and endoscopic re-intervention at 1, 3, and 6 months. Outcomes were compared using adjusted odds ratios (aOR) with 95% confidence intervals (CIs). Results: Before matching, vonoprazan users had higher baseline rates of obesity (31.5% vs 19.6%), ischemic heart disease (44.9% vs 27.9%), and anticoagulant use (59.1% vs 39.9%) (all P < 0.001). After matching, the cohorts were well-balanced (mean age 64 years; 50.4% woman). There was no statistically significant difference in 30-day rebleeding (7.9% vs 12.6%; aOR 0.59; 95% CI: 0.26–1.36; P = 0.21) or in emergency visits (aOR 1.69; 95% CI: 0.73–3.87; P = 0.21). However, vonoprazan was associated with significantly lower 1-month readmission rates (11.8% vs 29.1%; aOR 0.33; 95% CI: 0.17–0.63; P = 0.001) and at 3 months (18.1% vs 29.9%; aOR 0.52; 95% CI: 0.29–0.94; P = 0.028). No significant differences were observed in blood transfusion rates, endoscopic reintervention, or mortality at any timepoint. Conclusion: In this national, propensity-matched cohort study, vonoprazan was noninferior to intravenous PPIs in preventing 30-day peptic ulcer rebleeding following endoscopic hemostasis. Importantly, vonoprazan was associated with significantly lower hospital readmission rates at 1 and 3 months, highlighting its real-world utility and potential cost savings as an oral alternative to IV PPI therapy in peptic ulcer bleeding.