Proton Pump Inhibitors Are Associated with Reduced Incidence of Dysplasia in Barrett's Esophagus

Abstract

BACKGROUND AND AIMS: Esophageal acid exposure is important in the pathogenesis of Barrett's esophagus (BE), and possibly in the progression of BE to dysplasia and carcinoma. The aim of this study is to compare the development of dysplasia in BE patients treated with or without proton pump inhibitor (PPI) or histamine 2-receptor antagonist (H2RA). METHODS: We analyzed prospectively collected data by a single endoscopist on patients with BE in a VA (Veterans Affairs) setting over a 20-yr time period (1981-2000). A pathologist used standard criteria to diagnose BE/dysplasia. Pharmacy information after 1994 was retrieved from a computerized database, and from research files for the period before that. The receipt and the duration of H2RA and/or PPI use was compared between those with and without dysplasia. The incidence of dysplasia was examined in a Kaplan-Meier survival analysis stratified by PPI treatment status, and the risk of dysplasia was examined in a Cox multiple regression analysis controlling for demographic features, length of BE, and the year of BE diagnosis. RESULTS: We analyzed data for 236 unique veteran patients with a mean age at BE diagnosis of 61.5 yr, 86% Caucasian, and 98% male. During 1,170 patient-yr of follow-up, 56 patients developed dysplasia giving an annual incidence rate of 4.7%. Of those, 14 had high-grade dysplasia. The cumulative incidence of dysplasia was significantly lower among patients who received PPI after BE diagnosis than in those who received no therapy or H2RA; log rank test (p < 0.001). Furthermore, among those on PPIs, a longer duration of use was associated with less frequent occurrence of dysplasia. In multivariate analysis, the use of PPI after BE diagnosis was independently associated with reduced risk of dysplasia, hazards ratio: 0.25 (95% CI 0.13-0.47), p < 0.0001. Longer segments of BE and Caucasian race were other independent risk factors for developing dysplasia. In general, similar findings were observed when only cases with high-grade dysplasia were analyzed. CONCLUSIONS: These results indicate that PPI therapy is associated with a significant reduction in the risk of developing dysplasia in patients with BE. However, more studies are required to confirm this finding.