S2484 PCABs or PPIs for Cirrhotic Patients? A Real-World Analysis of Bleeding Outcomes Using TriNetX

Introduction: The comparative effectiveness of potassium-competitive acid blocker (PCABs) and proton pump inhibitors (PPIs) in preventing upper gastrointestinal bleeding (UGIB) in cirrhotic patients remains unclear. Although PPIs are commonly used for acid suppression, concerns exist about their potential risks, including infections and hepatic encephalopathy. This study compares the incidence of UGIB following initiation of PCAB versus PPI therapy in patients with cirrhosis. Methods: We performed a retrospective cohort study using TriNetX Research Network, a federated database of de-identified electronic health records. Data were collected from 134 healthcare organizations in 14 different countries. Adult patients (≥18 years) with a diagnosis of cirrhosis between January 1, 2016, and December 31, 2024, who were prescribed either PCAB or PPI, were identified. Patients with a history of UGIB within 6 months prior to drug initiation were excluded. Patients with PCAB exposure were also excluded if they had received a PPI within 6 months of PCAB initiation. Propensity score matching (1:1) was adjusted for demographic characteristics and known risk factors of UGIB. Kaplan-Meier survival analysis and univariate Cox proportional hazards models were used to assess the incidence of UGIB within 90 days of therapy initiation. The secondary outcomes included rebleeding, need for endoscopic intervention, and mortality. Results: A total of 790,065 adults with cirrhosis and 137,843,348 without were analyzed. Before propensity score matching (PSM), PCAB users were older and had higher rates of diabetes, dialysis, and anticoagulant/antiplatelet use, but lower rates of varices, alcohol use, and NSAID exposure (all P <0.001). After 1:1 PSM, 58 patients per group were matched. Within 90 days, UGIB incidence was significantly lower with PCABs than PPIs (OR 0.490; 95% CI, 0.261–0.921; P = 0.024). While endoscopic intervention rates were similar (P = 0.079), the PCAB group had significantly lower rebleeding rates (P = 0.010) and inpatient mortality (OR 0.294; 95% CI, 0.156–0.552; P < 0.001). Conclusion: PCAB use was associated with significantly lower odds of UGIB compared to PPI use. PCAB users also had lower rates of rebleeding and inpatient mortality, suggesting a safer bleeding profile in patients with Cirrhosis. These findings support re-evaluating acid suppression strategies in cirrhotic patients at high risk for bleeding.