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Nonaspirin nonsteroidal anti‐inflammatory drugs and gastric cancer risk after Helicobacter pylori eradication: A territory‐wide study
Author(s) -
Li Bofei,
Cheung Ka Shing,
Wong Ian YuHong,
Leung Wai Keung,
Law Simon
Publication year - 2021
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/cncr.33412
Subject(s) - medicine , helicobacter pylori , interquartile range , hazard ratio , proton pump inhibitor , clarithromycin , gastroenterology , aspirin , omeprazole , cancer , proportional hazards model , confidence interval
Background Despite Helicobacter pylori (HP) eradication, individuals can still develop gastric cancer (GC). Prior studies have demonstrated that nonaspirin nonsteroidal anti‐inflammatory drugs (NA‐NSAIDs) reduce the risk of GC, but this may be caused by immortal time bias and failure to adjust for HP status. The objective of this study was to investigate whether NA‐NSAIDs reduced the risk of GC in patients who undergo H. pylori eradication. Methods Adult patients who had received clarithromycin‐based triple therapy between 2003 and 2016 were identified from a territory‐wide health care database. Exclusion criteria included prior GC or GC diagnosed <6 months after HP eradication, prior gastrectomy, gastric ulcer after HP eradication, and failure of triple therapy. Covariates included age, sex, prior peptic ulcer disease, other comorbidities, and concurrent medications (aspirin, proton pump inhibitors, statins, and metformin). To avoid immortal time bias, NA‐NSAID use (≥90 days) was treated as a time‐dependent variable in a multivariable Cox model (time‐dependent analysis). Time‐independent analysis was also performed. Results During a median follow‐up of 8.9 years (interquartile range, 5.4‐12.6 years), 364 of 92,017 patients (0.4%) who underwent HP eradication developed GC. NA‐NSAID use was associated with a significant reduction in the risk of GC in time‐fixed analysis (adjusted hazard ratio [aHR], 0.65; 95% CI, 0.47‐0.90), but not in time‐dependent multivariable analysis (aHR, 1.35; 95% CI, 0.97‐1.87). Time‐dependent subgroup analyses also did not indicate any significant association between NA‐NSAID use and either cardia GC (aHR, 0.75; 95% CI, 0.27‐2.06) or noncardia GC (aHR, 1.28; 95% CI, 0.83‐1.98). Conclusions NA‐NSAID use was not associated with a reduced risk of GC among patients who underwent HP eradication. The chemopreventive effect of NA‐NSAIDs observed in prior studies may have been confounded by immortal time bias.