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

Abstract

Background & Aims Limited evidence suggests that proton pump inhibitors (PPI), non-steroidal anti inflammatory drugs (NSAID)/aspirin and statins may be associated with 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. Methods We conducted a nested case-control study in a cohort of patients with BE identified in the national Department of Veterans Affairs (VA) 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, NSAID/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 socio-economic status. Results 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=0.5). 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% CI, 0.42–0.97). Filled statin prescriptions were also associated with a reduction in EAC risk (0.55; 95% CI, 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. Conclusion This observational study indicates that in patients with Barrett’s esophagus using PPI, NSAID/aspirin or statin therapy might reduce the risk of developing esophageal adenocarcinoma.

Reduced Risk of Barrett’s Esophagus in Statin Users: Case–Control Study and Meta-Analysis

“…Several individual studies (3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)27) and 2 systematic reviews (that produced essentially identical results despite slightly different methodologies (16,17)) have reported that statin use, and particularly statin use combined with a cyclo-oxygenase inhibitor, is associated with a reduced incidence of esophageal adenocarcinoma. This has been reported in cohort studies and case-control studies of Barrett's patients and population-based studies compared to population-based controls, although not all studies are in agreement (28).…”

Carcinogenesis of Barrett’s esophagus: a review of the clinical literature

“…A study from Australia showed that patients who took aspirin at least weekly had significantly lower risks of [142]. In a nested case-control study of individuals with BE, an inverse association was found between filled NSAID/ aspirin prescriptions and EAC, which remained significant when adjusted for PPI prescription, among other factors (incidence density ratio 0.64, 95 % CI 0.42-0.97) [132]. Similarly, a recent meta-analysis demonstrated that compared to nonusers, individuals who have used aspirin or nonaspirin NSAIDs had a significantly reduced risk of EAC.…”

“…Epidemiological studies have shown that the long-term use of PPIs is associated with lower rates of dysplasia and EAC in patients with BE [122,124,[129][130][131], except for one study [132]. In two other studies, the early use of a PPIs after the diagnosis of BE was associated with a decreased risk of developing dysplasia or EAC [122,129] ( Table 4).…”

Role of chemoprophylaxis with either NSAIDs or statins in patients with Barrett’s esophagus

“…Since 2003, several observational studies comparing BE and EAC patients have been published (Table 1). These were either case-control retrospective [23,37,38] or cohort studies [39][40][41][42][43] . Prospective chemoprevention trials are underway to evaluate the efficacy of aspirin and NSAIDs.…”

“…Kantor et al [43] reported that non-aspirin NSAID use reduced the risk of neoplastic progression but not aspirin use. The other 3 cohort studies were negative [41][42][43] , although Kantor found that NSAID use was beneficial only for patients with high-grade dysplasia. A pooled analysis of 6 population-based studies within the Barrett's and Esophageal Adenocarcinoma Consortium have shown that daily NSAID use can reduce the risk of developing EAC by more than 40% (OR = 0.56, 95%CI: 0.43-0.73, P < 0.001) [47] .…”