Statin use and gastric cancer risk in H. pylori-eradicated subjects: A territory-wide cohort study with propensity score adjustment

Abstract

Introduction: Despite successful H. pylori (HP) eradication, some individuals can still progress to gastric cancer (GC). Although statin has been shown to reduce the risk of gastric cancer, the results are largely confounded by the presence of HP infection. The aim of this study was to explore the potential effects of statin uses on gastric cancer development in a large cohort of HP-eradicated subjects. Aims and Methods: This cohort study was based on the territory-wide electronic healthcare database of Hong Kong, from which all subjects prescribed with clarithromycin-based triple therapy for HP infection between 2003 and 2012 were identified. The observation period commenced from the date of HP therapy and the follow-up was censored at GC diagnosis, death or study end date (December 2015). Statin use was defined as 430-day use during the study period. Exclusion criteria included GC diagnosed within the first year of HP therapy, prior history of GC or gastrectomy, and failure of HP eradication. The hazard ratio (HR) of GC with statin use was estimated by Cox model with propensity score adjustment for other variables (age, sex, comorbiditiesand other medications use). Results: In total, 63,605 HP eradicated patients were included in analysis including 15,990 (25.1%) statin users. During a median follow-up of 7.6 (IQR: 5.1–10.3) years, 169 (0.27%) developed GC (incidence rate: 3.5 per 10,000 personyears) and the median age at gastric cancer diagnosis was 71.1 (IQR 61.6–81.8) years. The median cumulative defined daily dose (cDDD) of statin users was 432. A lower GC risk was observed in statin users (HR derived from propensity score adjustment with trimming 0.30; 95% CI 0.18–0.52) than non-users. The propensity score adjusted absolute risk difference between statin and non-statin use was 2.76 fewer gastric cancers (95% CI 1.89–3.24) per 10,000 person-years. By stratified analysis, the protective effect of statin was significant for non-cardia cancer (HR 0.27; 95% CI 0.14–0.52), but not for cardia cancer (HR 0.39; 95% CI 0.14 -1.07). There was also a significant trend towards lower GC risk with increasing duration and dose of statin (p-trend50.001). Conclusion: In this territory-wide study, statin use was associated with a significantly lower risk of GC development among HP-eradicated patients, in a duration-and dose-response manner.