Statin use and gastric cancer risk in Helicobacter pylori-eradicated patients: a territory-wide study with propensity score matching

Abstract

Introduction: Despite successful Helicobacter pylori eradication, some individuals still progress to develop gastric cancer (GC). Although statins were shown to reduce GC risk, the results are largely confounded by H pylori status. The aim of this study was to investigate the effects of statins on GC development in H pylori–eradicated patients. Methods: This was a cohort study using a territory-wide electronic healthcare database. All adult patients (≥18 years) who were prescribed clarithromycin-based triple therapy for H pylori infection between 2003 and 2012 were recruited. The observation period commenced from the date of H pylori therapy and follow-up was censored at GC diagnosis, death, or study end date (December 2015). Statin use was defined as >180-day use during the study period. Exclusion criteria included GC diagnosed within the first year of H pylori therapy, a history of GC or gastrectomy, and failure of H pylori eradication. The subdistribution hazard ratio (SHR) of GC with statin use was estimated by competing risk regression with propensity score (PS) matching for other variables (age, sex, co-morbidities, and other medications). Results: A total of 63 605 patients were recruited, with the mean (± standard deviation) age of receiving triple therapy being 55.6 ± 14.6 years. There were 29 640 (46.6%) men and 15 990 (25.1%) statin users. During a median follow-up of 7.6 years (interquartile range, 5.1-10.3 years), 169 (0.27%) of 63 605 patients developed GC (crude incidence rate: 3.5 per 10 000 person-years for the whole cohort; 2.4 vs 3.8 per 10 000 person-years for statin and non-statin users, respectively). A total of 22 870 patients were available for PS matching. A lower GC risk was observed in statin users (SHR=0.34; 95% confidence interval [CI]=0.19-0.61), with a PS-adjusted absolute risk difference between statin and non-statin use being 2.6 fewer GC (95% CI=1.56-3.12) per 10 000 person-years. A lower GC risk was observed with a longer duration of statin use (SHR=0.46; 95% CI= 0.25-0.86 for <5 years of use and SHR 0.43; 95% CI=0.29-0.66 for ≥5 years of use, Ptrend<0.001). In addition, the SHR of GC with every 100 increases in cumulative defined daily doses of statins was 0.90 (95% CI=0.81-0.99). Conclusions: Statin use is associated with a significantly lower GC risk among H pylori–eradicated patients, in a duration- and dose-response manner.