Risks of long-term use of proton pump inhibitor on ischemic vascular events: A distributed network analysis of 5 real-world observational Korean databases using a common data model

Background: Proton pump inhibitors (PPIs) are frequently prescribed drugs. However, it has been suggested that they are associated with an increased risk of ischemic vascular events (IVE) including stroke, although the data are inconsistent. Aims: We investigated the association between PPIs use and IVE in five observational Korean databases using a common data model (CDM). Methods: This study included patient-based retrospective, observational cohort data of subjects aged over 18 years between January 1, 2004, and December 31, 2020, from five medical centers as part of the Observational Medical Outcomes Partnership (OMOP) CDM. Subjects who were included in both cohorts or had a previous history of ischemic stroke were excluded. After propensity matching, 8007 propensity-matched pairs between the PPIs and H-2 receptor antagonist (H(2)RA) users were included in this study. Results: In the 1:1 propensity score matching with 8007 in each group, long-term PPIs use (> 365 days) was not associated with ischemic stroke (odds ratio (OR) = 1.05, 95% confidence interval (CI) 0.71-1.56; I-2 = 57%), ischemic stroke and transient ischemic attack (OR = 1.02, 95% CI 0.71-1.48; I-2 = 53%), and net adverse clinical events (OR = 1.08, 95% CI 0.83-1.40; I-2 = 47%) compared with H2RAs users. Conclusions: Our analysis in a large dataset found no evidence that long-term use of PPIs was associated with an increased risk of ischemic stroke.