S1035 Potassium-Competitive Acid Blockers vs Proton Pump Inhibitors: A Real-World Comparative Effectiveness Study

Introduction: Gastroesophageal reflux disease (GERD) is a common condition that significantly impairs quality of life and may lead to serious complications. Proton pump inhibitors (PPIs) are widely used but limited by delayed onset, variable efficacy, and incomplete symptom relief in some patients. Potassium-competitive acid blockers (PCABs), which provide rapid and sustained acid suppression, have emerged as a promising alternative. This study compared real-world clinical outcomes of PCABs versus PPIs in patients with GERD and related acid-mediated disorders. Methods: A retrospective cohort study was conducted using the TriNetX research network. Adult patients diagnosed with GERD, esophagitis, or peptic ulcer disease who received a PCAB or PPI were included. Propensity score matching (1:1) was performed to balance cohorts for demographics, comorbidities, antiplatelet and anticoagulant use, Helicobacter pylori status, and nonsteroidal anti-inflammatory drug exposure. The primary outcome was gastrointestinal (GI) bleeding. Secondary outcomes included hospitalization, need for critical care, GI perforation, Clostridioides difficile infection (CDI), need for endoscopy, transfusion, and overall mortality. Logistic regression was used to estimate odds ratios (ORs) with 95% confidence intervals (CIs). Results: After matching, 1,726 patients were included in each group with balanced baseline characteristics. Men comprised 56.9% of the PCAB group and 55.9% of the PPI group; over 80% were White. At 2-year follow-up, PCABs were associated with significantly better outcomes. Compared to PPIs, PCABs had lower risks of GI bleeding (OR 0.47; 95% CI 0.25-0.86), critical care need (OR 0.29; 95% CI 0.20-0.42), hospitalization (OR 0.42; 95% CI 0.32-0.54), and overall mortality (OR 0.23; 95% CI 0.15-0.34). PCABs also had lower odds of CDI (OR 0.57; 95% CI 0.37-0.89), esophagogastroduodenoscopy (OR 0.80; 95% CI 0.66-0.97), and transfusion (OR 0.21; 95% CI 0.12-0.37). No significant difference was seen in GI perforation (OR 1.01; 95% CI 0.42-2.43). Conclusion: In this large real-world matched cohort, PCABs were associated with superior outcomes compared to PPIs, including reduced risks of GI bleeding, hospitalization, intensive care, and death. These findings support PCABs as a potential alternative to PPIs, particularly for high-risk or treatment-resistant patients. Prospective studies are warranted to confirm these benefits and assess long-term safety.