Proton Pump Inhibitors Use in Patients With Ischemic Stroke on Dual Antiplatelet Therapy at Low Risk of Upper Gastrointestinal Bleeding

Background Current guidelines lack recommendations regarding the use of proton pump inhibitors (PPIs) for preventing upper gastrointestinal bleeding (UGIB) among patients at low risk for UGIB treated with dual antiplatelet therapy for ischemic stroke (IS). Our objective was to assess the effectiveness of PPIs in lowering the risk of significant UGIB in this patient group. Methods and Results A retrospective cohort study was conducted involving patients at low risk for UGIB admitted for IS between 2014 and 2018 and treated with dual antiplatelet therapy. The study used a nationwide claims database in Korea. The primary end point was significant UGIB during 12 months after IS. To evaluate the risk of significant UGIB based on PPI use, we performed a multivariable Cox regression analysis. Subgroup analyses and propensity score matching analysis were conducted for validation. Among 96 722 patients with IS at low risk for UGIB who were on dual antiplatelet therapy (mean age, 67.0 years; men: 63.0%), 16 084 (16.6%) were treated with PPIs. During 12 months of follow‐up, 325 patients experienced significant UGIB, and 479 experienced any UGIB. PPI use was associated with a reduced risk of significant UGIB (hazard ratio, 0.63 [95% CI, 0.45–0.89]; P =0.009). This association was consistent in the subgroup and propensity score matching analyses. Conclusions In patients with IS receiving dual antiplatelet therapy, PPI use reduced the risk of significant UGIB by 37% on average, even among low‐risk patients. However, the use of PPIs in this patient group was limited, highlighting the need for additional prospective studies.