Proton Pump Inhibitor Use Was Not Associated With Reduced Gastrointestinal Bleeding Risk in Ischemic Stroke Patients Treated With Dual Antiplatelet Therapy

Background To evaluate the association between proton pump inhibitor (PPI) use and gastrointestinal bleeding (GIB) in acute ischemic stroke (AIS) patients receiving dual antiplatelet therapy (DAPT). Methods This retrospective study analyzed 3,122 AIS patients with large artery atherosclerosis (LAA) treated with DAPT at Qingdao University Affiliated Hospital (September 2020–December 2023). Adjusted odds ratios (aORs) for GIB were calculated using binary logistic regression, controlling for confounders including age, sex, and other baseline characteristics. To address confounding by indication, we additionally performed 1:1 propensity score matching (PSM) as a sensitivity analysis, with conditional logistic regression applied to the matched cohort. Results 45.0% (n=1,404) received concomitant PPI. No significant difference in GIB incidence was observed between PPI users and non-PPI users (2.1% vs. 1.3%, p = 0.12). Subgroup analyses revealed that PPI use was significantly associated with increased GIB risk in non-endovascular therapy patients (aOR = 2.08, p = 0.03), particularly those with posterior circulation infarction (aOR = 5.96, p = 0.006). These findings were further supported by propensity score matching analysis (conditional OR = 1.64, 95% CI 0.87–3.09, p = 0.124 for the overall cohort; conditional OR = 12.29, 95% CI 1.59–94.90, p = 0.016 for posterior circulation infarction in the non-endovascular subgroup). No significant association between PPI use and GIB risk was found in endovascular therapy or age-stratified subgroups. Conclusion PPI use was not associated with reduced overall GIB risk in DAPT-treated AIS patients. Routine PPI prophylaxis may be unnecessary for low-bleeding-risk populations, while the association observed in posterior circulation infarction remains hypothesis-generating and warrants prospective validation.