Statin Use Reduces Risk of Esophageal Adenocarcinoma in US Veterans with Barrett's Esophagus: A Nested Case-Control Study

Background and Aims Statins have been reported to protect against esophageal adenocarcinoma (EAC) in patients with Barrett's esophagus (BE). However, there are few data from adequately powered cohort studies of subjects with BE. Methods We conducted a nested case-control study of a cohort of BE patients identified from national Veteran Affairs (VA) outpatient files, diagnosed with BE from 2004 through 2009. New cases of EAC recorded after BE diagnosis were identified during a follow-up period that ended in 2011 and verified using electronic medical records. We selected patients with BE without EAC (controls) using incidence density sampling; 3 controls were matched to each case based on birth year and date of BE diagnosis. Our analysis included only male patients with at least 1 VA visit per year of follow up. We identified prescriptions for statins and non-statin lipid lowering medications filled after BE diagnosis and up to 90 days before EAC diagnosis for cases and controls (during the corresponding time period); we examined the association between statin use and EAC in conditional logistic regression models. Results We compared 311 EAC cases to 856 controls. Cases were less likely to use any statins than controls (40.2% vs 54.0%; P <.01). Significantly lower proportions of cases used statins for 6-18 months (10.0% cases vs 17.1% controls) and >18 months (19.3% vs 24.0%, respectively; P <.01). Simvastatin was the most commonly prescribed statin (accounting for 86.9% of statin use); the defined daily dose of simvastatin was lower in cases than in controls (21-40 mg/day, 9.3% vs 14.5%, respectively; and >40 mg/day, 8.4% vs 12.6%, respectively; P <.01). In multivariate analysis, statin use was inversely associated with development of EAC (adjusted odds ratio [OR], 0.65; 95% confidence interval [CI], 0.47-0.91). This protective association was strongest for patients with advanced-stage EAC: in a stratified analysis, comparison of 189 cases with stage 0-1 EAC to 520 controls produced an adjusted OR of 0.85 (95% CI, 0.54-1.33). Among patients with late-stage EAC (stages 2-4, n = 106) and 291 controls, the adjusted OR was 0.44 (95% CI, 0.25-0.79). We found no association between EAC and non-statin lipid-lowering medications. Conclusions In a case-control study of US veterans, statin use among those with BE appeared to decrease the risk of EAC. This protective effect was strongest against advanced-stage EAC, and increased with statin dose.