Proton pump inhibitor use and risk of stroke: A systematic review and meta-analysis

Objective: To explore a link between the use of proton pump inhibitor (PPI) and the risk of stroke.

Methods: Comprehensive literature search in PubMed, EMBASE, and Cochrane CENTRAL Library databases was carried out for observational studies establishing the link between PPI and a risk of stroke. Data extraction and quality assessment were performed by two reviewers. Pooled hazard ratios (HRs) with 95% confidence intervals (CIs) using random-effects models were plotted. Subgroup analyses were conducted based on age, gender, PPI type, duration of follow-up, and propensity score matching (PSM).

Results: The analysis included 12 studies, with considerable heterogeneity (I2 = 95%). PPI use did not affect the incidence of ischemic stroke (HR: 1.11, 95% CI: 0.98-1.26). Subgroup analyses revealed that PPI use correlated with the risk of ischemic stroke, in particular in patients<65 years old (HR: 1.25, 95% CI: 1.07-1.45), both males (HR: 1.12, 95% CI: 1.02-1.24) and females (HR: 1.21, 95% CI: 1.10-1.33). The correlation varied depending on the PPI type, with pantoprazole showing elevated risk (HR: 1.66, 95% CI: 1.43-1.93). Duration of follow-up or propensity score matching (PSM) did not impact the association.

Conclusion: PPI use may be linked with ischemic stroke, particularly in individuals <65 years old and of all genders. The specific PPI type may also influence the risk. However, the cumulative analysis did not find any statistically significant association, and heterogeneity among studies was substantial.