Dose‐dependent association of proton pump inhibitors use with gastric intestinal metaplasia among Helicobacter pylori‐positive patients

BACKGROUND: Gastric intestinal metaplasia is a pre‐cancerous condition associated with multiple factors. OBJECTIVE: We evaluated whether cumulative proton pump inhibitor dose is associated with the diagnosis of gastric intestinal metaplasia while controlling for multiple variables. METHODS: We retrospectively identified patients who underwent upper endoscopy with gastric biopsy between 2005 and 2014. Covariate data retrieved included age, sex, ethnicity, smoking status, Helicobacter pylori status (based on clarithromycin‐amoxicillin‐proton pump inhibitor issued), cumulative proton pump inhibitor issued within 10 years (quartiles [PPI‐Q(1–4)] of daily drug dose), anti‐parietal cell antibodies, body mass index and comorbidity index. RESULTS: Of the 14,147 included patients (median age 63.4 years; women 54.4%; Helicobacter pylori‐positive 29.0%), 1244 (8.8%) had gastric intestinal metaplasia. Increasing age, Helicobacter pylori infection, smoking, anti‐parietal cell antibodies and proton pump inhibitor use were all associated with the diagnosis of gastric intestinal metaplasia. Upper quartiles of cumulative proton pump inhibitor doses (PPI‐Q(4) and PPI‐Q(3) vs. PPI‐Q(1)) were associated with the diagnosis of gastric intestinal metaplasia: adjusted odds ratios 1.32 (95% confidence interval [CI] 1.111.57) and 1.27 (95% CI 1.07–1.52), respectively, for the whole cohort (P(total) 0.007, P(trend) 0.013), 1.69 (95% CI 1.23–2.33) and 1.40 (95% CI 1.04–1.89), respectively, for Helicobacter pylori‐positive patients (P(total) 0.004, P(trend) 0.005) and 1.21 (95% CI 0.98–1.49) and 1.20 (95% CI 0.96–1.49), respectively, for Helicobacter pylori‐negative patients (P(total) 0.288, P(trend) 0.018). Upper quartiles of proton pump inhibitor dose were associated with a 5–10‐fold increased risk of low‐grade dysplasia. CONCLUSIONS: Among Helicobacter pylori‐positive patients, proton pump inhibitor use appears to be associated with a dose‐dependent increased likelihood of gastric intestinal metaplasia.