Nonsteroidal Anti-Inflammatory Drug Use is Not Associated With Reduced Risk of Barrett's Esophagus

Abstract

Objectives: Regular use of nonsteroidal anti-inflammatory drugs (NSAIDs) is associated with a reduced risk of esophageal adenocarcinoma. Epidemiological studies examining the association between NSAID use and the risk of the precursor lesion, Barrett's esophagus, have been inconclusive.

Methods: We analyzed pooled individual-level participant data from six case-control studies of Barrett's esophagus in the Barrett's and Esophageal Adenocarcinoma Consortium (BEACON). We compared medication use from 1,474 patients with Barrett's esophagus separately with two control groups: 2,256 population-based controls and 2,018 gastroesophageal reflux disease (GERD) controls. Study-specific odds ratio (OR) and 95% confidence intervals (CI) were estimated using multivariable logistic regression models and were combined using a random-effects meta-analytic model.

Results: Regular (at least once weekly) use of any NSAIDs was not associated with the risk of Barrett's esophagus (vs. population-based controls, adjusted OR=1.00, 95% CI=0.76-1.32, I²=61%; vs. GERD controls, adjusted OR=0.99, 95% CI=0.82-1.19, I²=19%). Similar null findings were observed among individuals who took aspirin or non-aspirin NSAIDs. We also found no association with highest levels of frequency (at least daily use) and duration (≥5 years) of NSAID use. There was evidence of moderate between-study heterogeneity; however, associations with NSAID use remained non-significant in "leave-one-out" sensitivity analyses.

Conclusions: Use of NSAIDs was not associated with the risk of Barrett's esophagus. The previously reported inverse association between NSAID use and esophageal adenocarcinoma may be through reducing the risk of neoplastic progression in patients with Barrett's esophagus.

Figure 1. Associations between NSAID use and risk of Barrett's esophagus

The summary odds ratios and 95% confidence intervals (CI) for the association between Barrett's esophagus and A) at least weekly aspirin use; B) at least weekly non-aspirin NSAID use; and C) at least weekly use of any NSAIDs. Summary odds ratios and 95% confidence intervals were estimated using a random-effects meta-analytic model. All statistical tests were two-sided. % Weight describes the weighting each study contributes to the summary odds ratio. The dot on each square represents the study-specific odds ratio, and the size of the surrounding square is an illustrative representation of study weighting. The horizontal lines represent the confidence intervals; if ending in an arrow, this indicates that the interval transcends the region plotted. The diamond represents the summary odds ratio and 95% confidence intervals. Houston = the Houston Barrett's Esophagus study; FINBAR = Factors Influencing the Barrett's Adenocarcinoma Relationship Study; KPNC = the Epidemiology and Incidence of Barrett's Esophagus study; NDB = The Newly Diagnosed Barrett's Esophagus Study; SDH = the Study of Digestive Health; SRD = the Study of Reflux Disease.

Figure 1. Associations between NSAID use and risk of Barrett's esophagus

The summary odds ratios and 95% confidence intervals (CI) for the association between Barrett's esophagus and A) at least weekly aspirin use; B) at least weekly non-aspirin NSAID use; and C) at least weekly use of any NSAIDs. Summary odds ratios and 95% confidence intervals were estimated using a random-effects meta-analytic model. All statistical tests were two-sided. % Weight describes the weighting each study contributes to the summary odds ratio. The dot on each square represents the study-specific odds ratio, and the size of the surrounding square is an illustrative representation of study weighting. The horizontal lines represent the confidence intervals; if ending in an arrow, this indicates that the interval transcends the region plotted. The diamond represents the summary odds ratio and 95% confidence intervals. Houston = the Houston Barrett's Esophagus study; FINBAR = Factors Influencing the Barrett's Adenocarcinoma Relationship Study; KPNC = the Epidemiology and Incidence of Barrett's Esophagus study; NDB = The Newly Diagnosed Barrett's Esophagus Study; SDH = the Study of Digestive Health; SRD = the Study of Reflux Disease.

Figure 1. Associations between NSAID use and risk of Barrett's esophagus

The summary odds ratios and 95% confidence intervals (CI) for the association between Barrett's esophagus and A) at least weekly aspirin use; B) at least weekly non-aspirin NSAID use; and C) at least weekly use of any NSAIDs. Summary odds ratios and 95% confidence intervals were estimated using a random-effects meta-analytic model. All statistical tests were two-sided. % Weight describes the weighting each study contributes to the summary odds ratio. The dot on each square represents the study-specific odds ratio, and the size of the surrounding square is an illustrative representation of study weighting. The horizontal lines represent the confidence intervals; if ending in an arrow, this indicates that the interval transcends the region plotted. The diamond represents the summary odds ratio and 95% confidence intervals. Houston = the Houston Barrett's Esophagus study; FINBAR = Factors Influencing the Barrett's Adenocarcinoma Relationship Study; KPNC = the Epidemiology and Incidence of Barrett's Esophagus study; NDB = The Newly Diagnosed Barrett's Esophagus Study; SDH = the Study of Digestive Health; SRD = the Study of Reflux Disease.