Medications (NSAIDs, Statins, Proton Pump Inhibitors) and the Risk of Esophageal Adenocarcinoma in Patients With Barrett's Esophagus

Abstract

Limited evidence suggests that proton pump inhibitors (PPI), nonsteroidal anti-inflammatory drugs (NSAID)/aspirin, and statins may be associated with a low risk of esophageal neoplasia. However, the possible effect these medications may have on the risk of esophageal adenocarcinoma (EAC) in patients with existing Barrett's esophagus (BE) is unclear. We conducted a nested case-control study in a cohort of patients with BE identified in the national Department of Veterans' Affairs computerized databases. Cases with incident EAC were matched by incidence density sampling to controls with BE who remained without EAC at the date of the EAC diagnosis for the corresponding case. We identified prescriptions for PPI, NSAIDs/aspirin, and statins that were filled between BE diagnosis and EAC diagnosis. Incidence density ratios were calculated using conditional logistic regression models that adjusted for race, outpatient encounters, a disease comorbidity index, and socioeconomic status. In a cohort of 11,823 patients with first-time BE diagnosis, we examined 116 EAC cases and 696 matched controls. Most cases and controls had at least one filled PPI prescription (95% vs 94%; P = .5). In this setting of almost universal PPI use, filled NSAID/aspirin prescriptions were associated with a reduced risk of EAC (adjusted incidence density ratio, 0.64; 95% confidence interval, 0.42-0.97). Filled statin prescriptions also were associated with a reduction in EAC risk (0.55; 95% confidence interval, 0.36-0.86), with a significant trend toward greater risk reduction with longer duration of statin use. However, the strong inverse associations with even short periods of use raise concerns of uncontrolled confounding. This observational study indicates that in patients with BE using PPI, NSAID/aspirin, or statin therapy might reduce the risk of developing EAC.