Chemoprevention of Barrett’s Esophagus: a Systematic Review and Comprehensive Assessment of Bias

Summary Chemoprevention of Barrett’s esophagus (BE) represents an opportunity to reduce the burden of esophageal adenocarcinoma (EAC). We conducted a systematic review and meta-analysis to evaluate the assumed causal association between proton-pump inhibitors (PPIs), aspirin and statins, and BE progression, and undertook a comprehensive risk of bias (RoB) assessment. The protocol was prospectively registered (PROSPERO ID: CRD42024532338). Sixteen observational studies and one randomized controlled trial were identified. PPIs and statins were associated with a 54% (adjusted OR 0.46; 95% CI 0.25–0.86; P = 0.02) and 47% (adjusted OR 0.53; 95% CI 0.37–0.74; P < 0.001) reduced odds of progression, and aspirin use was not significantly associated (adjusted OR 0.84; 95% CI 0.65–1.08; P = 0.17). Among observational studies, 6 were at critical RoB and 10 were at serious RoB. The only trial included was at low RoB and reported no significant associations for aspirin and PPI comparisons and high-grade dysplasia (HGD)/EAC. The Grading of Recommendations, Assessment, Development and Evaluations certainty of evidence was very low. All observational studies were at serious or critical RoB. Trial evidence was at low RoB and did not demonstrate any significant differences between aspirin and PPI comparisons for the outcome of HGD/EAC. Given the very low certainty of evidence, there is little rationale to recommend these medications for chemoprevention in BE.