NSAIDs, statins, low-dose aspirin and PPIs, and the risk of oesophageal adenocarcinoma among patients with Barrett's oesophagus: a population-based case–control study

Abstract

ObjectivesNon-steroidal anti-inflammatory drugs (NSAIDs), proton pump inhibitors (PPIs), low-dose aspirin and statins may decrease the risk of oesophageal adenocarcinoma (OAC) among patients with Barrett's oesophagus (BO). However, previous studies did not adequately address bias and confounding. Our objective was to estimate the risk of OAC among patients with BO exposed to NSAIDs, statins and PPIs.DesignCase–control study nested within a BO cohort.SettingTwo primary care databases (the UK and the Netherlands (NL)).ParticipantsCases were adults ≥18 years of age with OAC or high-grade dysplasia (HGD) diagnosis ≥1 year after BO diagnosis. Controls were matched on age, sex, year of BO diagnosis and database.ExposureDrug use was assessed from BO diagnosis until matching date.Outcome measureAdjusted ORs with 95% CI were calculated by conditional logistic regression.ResultsWithin the BO cohort (n=15 134), 45 OAC (UK: 40, NL: 5) and 12 HGD cases (NL: 12) were identified. ORa for OAC during NSAID use was 1.2 (95% CI 0.6 to 2.5) and during statin use for >3 years 0.5 (95% CI 0.1 to 1.7). When including HGD cases (n=57), ORa for NSAID use was 0.9 (95% CI 0.5 to 1.8) and for statin use >3 years 0.5 (95% CI 0.1 to 1.7). Higher doses of statins showed lower estimates for OAC and HGD, though not statistically significant. Low-dose aspirin and PPIs did not significantly decrease the risk of OAC and HGD.ConclusionsIn this population-based nested case–control study, use of NSAIDs, PPIs, low-dose aspirin or statins did not reduce the risk of HGD and OAC among patients with BO. These findings indicate that for an unselected group of patients with BO chemoprevention by use of drugs to reduce progression to HGD and OAC should not be directly considered as routine care.

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

“…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). Within the progression to cancer it is not clear whether the effects of statin (and aspirin) are seen mainly at the points of development and maintenance of the Barrett's segment or on preventing progression to dysplasia and cancer.…”

Aspirin acts in esophageal cancer: a brief review

“…Although it is reported effective of aspirin in reducing the incidence of Barrett's esophagusderived esophageal adenocarcinoma (31), epidemiological evidences of aspirin on the risk of Barrett's esophagus remain inadequate to reach a definitive conclusion (32). Another nested case-control study failed to demonstrate the association between aspirin or non-aspirin NSAIDs and esophageal cancer (33). These findings indicate that the targeting procedures of antitumor activity of aspirin may be the neoplastic progression from Barrett's esophagus to adenocarcinoma or the metastasis of tumor cells other than the development into Barrett's esophagus from normal epithelial tissue.…”

“…As a COX-2 inhibitor, aspirin may not only affect the inflammatory pathologies but decrease the proliferation of different types of cancer cells through these interrelated signaling pathways as well. Furthermore, COX-2 has also been shown to be related to the development from Barrett's esophagus to esophageal adenocarcinoma (42,43), which explains why the probable targeting procedures in antitumor activity of aspirin is the neoplastic progression from Barrett's esophagus to adenocarcinoma other than the development into Barrett's esophagus from normal epithelial tissue (33).…”

Barrett’s esophagus: best practices for treatment and post-treatment surveillance

“…However, a randomized trial studying the use of celecoxib in chemoprevention demonstrated that celecoxib did not appear to prevent the transformation of dysplastic BE to EAC (41). A populationbased case control study evaluating the use of low-dose aspirin or NSAIDs published in 2015 was also unable to show a reduction in risk of HGD and EAC in patients with BE (42). Given the uncertainty of the currently available data and the potential risks of long-term NSAID use, their use exclusively for the prevention of EAC in patients with BE cannot be recommended at this time (12).…”