Do Proton Pump Inhibitors Reduce Upper Gastrointestinal Bleeding in Older Patients with Atrial Fibrillation Treated with Oral Anticoagulants? A Nationwide Cohort Study in France

Background Proton pump inhibitors (PPIs) are largely used in older adults and data are needed in off-label indications, such as the prevention of upper gastrointestinal bleeding (UGIB) in patients receiving oral anticoagulants (OACs). This study aimed to assess whether PPIs reduce the risk of UGIB in patients initiating oral anticoagulation. Methods We conducted a longitudinal study based on the French national health database. The study population included 109,693 patients aged 75–110 years with a diagnosis of atrial fibrillation who initiated OACs [vitamin K antagonist (VKA) or direct OAC (DOAC)] between 2012 and 2016. We used multivariable Cox models weighted by inverse of probability of treatment to estimate the adjusted hazard ratio (aHR) of UGIB between PPI users and nonusers over a 6- and 12-month follow-up. Results PPI users represented 23% of the study population (28% among VKA initiators and 17% among DOAC initiators). The mean age (83 ± 5.3 years) and proportion of women (near 60%) were similar between groups. The risk of UGIB in the first 6 months after initiation of OAC decreased by 20% in PPI users compared with PPI nonusers [aHR 6 months = 0.80, 95% confidence interval (CI) 0.65–0.98], but was not significantly modified when the follow-up was extended to 12 months (aHR 12 months = 0.90, 95% CI 0.76–1.07), with a stronger effect among patients treated with vitamin K antagonists (aHR 6 months = 0.73, 95% CI 0.58–0.93; aHR 12 months = 0.81, 95% CI 0.67–0.99). Conclusions This study suggests that PPIs were associated with reduced risk of gastrointestinal bleeding after initiation of oral anticoagulation in older patients with atrial fibrillation, particularly within 6 months after initiation of an antivitamin K antagonist.