S876 Aspirin Plus Proton Pump Inhibitor Therapy Reduces Progression to Esophageal Adenocarcinoma in Barrett’s Esophagus: A Real-World Propensity-Matched Cohort Study

Introduction: Barrett's esophagus (BE) is a precancerous condition associated with increased risk of progression to esophageal adenocarcinoma (EAC). Aspirin and proton pump inhibitors (PPIs) have been investigated for their potential chemopreventive effects in BE. Real-world comparative data between combination aspirin plus PPI therapy versus PPI monotherapy for preventing progression to esophageal adenocarcinoma remain limited. Methods: We conducted a retrospective cohort study using the TriNetX U.S. Collaborative Network, a federated electronic health record database. Adult patients with BE who were treated with aspirin plus PPI or PPI alone were identified. Patients with high-grade dysplasia were excluded from the analysis. Propensity score matching (1:1) was performed on demographics (age, gender, race), comorbidities (overweight and obesity, gastroesophageal reflux disease, diaphragmatic hernia, nicotine dependence, type 2 diabetes mellitus, essential hypertension, Helicobacter pylori infection, and alcohol dependence). The primary outcome was progression to EAC during follow-up. Results: A total of 137,204 patients in the aspirin plus PPI cohort and 152,218 patients in the PPI-only cohort met inclusion criteria. After propensity score matching, 104,452 patients remained in each cohort with well-balanced baseline characteristics. The mean age was 63.7 ± 11.5 years in the aspirin plus PPI group and 64.0 ± 11.6 years in the PPI-only group. At follow-up, progression to EAC occurred in 304 patients (0.291%) in the aspirin plus PPI group compared to 402 patients (0.386%) in the PPI-only group. The combination therapy was associated with a significant risk reduction (risk ratio = 0.754; 95% confidence interval [CI] 0.650-0.875, risk difference = -0.095%, 95% CI -0.145% to -0.045%, P = 0.0002). Conclusion: In this real-world analysis, treatment with aspirin plus PPI was associated with lower rates of progression to EAC compared to PPI monotherapy in patients with BE over the study period. The 0.095% absolute risk reduction and 24.6% relative risk reduction demonstrate a clinically meaningful chemopreventive benefit of combination therapy. The highly significant P-value (P = 0.0002) provides strong statistical evidence for this protective effect. These findings support the role of aspirin as an adjunctive chemopreventive agent in BE management, suggesting that the anti-inflammatory and antiplatelet properties of aspirin may provide additional protection beyond acid suppression alone.