Acid-suppressive medications and risk of esophageal adenocarcinoma in patients with Barrett’s esophagus: A systematic review and meta-analysis.

11 Background: Acid-suppressive medications, particularly proton pump inhibitors (PPI), may modify risk of esophageal adenocarcinoma (EAC) in patients with Barrett’s esophagus (BE). We performed a systematic review and meta-analysis of studies evaluating the association between PPIs and histamine receptor antagonists (H2RA) and risk of EAC or high-grade dysplasia (BE-HGD) in patients with BE. Methods: Through a systematic search up to June 2013, we identified 7 observational studies (5 cohort studies and 2 case-control studies; 2,813 patients with BE, 317 cases of EAC and/or BE-HGD, 84.4% PPI users) reporting the association between PPIs or H2RA and EAC in patients with BE. Summary odds ratio (OR) with 95% confidence intervals (CI) was estimated using random effects model, and heterogeneity was measured using the inconsistency index (I2). Results: On meta-analysis, PPI use was associated with 71% reduction in EAC risk in patients with BE (adjusted OR, 0.29; 95% CI, 0.12-0.71). There was a trend toward a dose-response relationship with PPI use for >2 years protective against EAC [3 studies; PPI use >2 years vs. <2 years (as compared to no use): OR, 0.45 (0.19-1.06) vs. 1.09 (0.47-2.56)]. Considerable heterogeneity was observed in the overall analysis (I2=81%). On restricting analysis to 5 cohort studies, use of PPIs was consistently associated with a lower risk of EAC and/or BE-HGD (adjusted OR, 0.33; 95% CI, 0.19-0.58; I2=9%). H2RA use was not associated with decreased risk of EAC in patients with BE based on 2 studies (adjusted OR, 1.15; 95% CI, 0.77-1.72). Using a 67% summary risk reduction (derived from cohort studies) of EAC and/or BE-HGD with PPI use in patients with BE, and observed cumulative incidence rates of EAC and/or BE-HGD in patients with BE overall as 10.2 per 1,000 patient years, we estimate the number needed to treat with PPIs to prevent 1 case of EAC or BE-HGD in BE patients at 147. Conclusions: Based on meta-analysis of observational studies, the use of PPI, but not H2RA appears to be associated with a decreased risk of EAC and/or BE-HGD in patients with BE. PPI use should be considered in BE, and chemopreventive trials of PPIs in patients with BE are warranted.