Vonoprazan vs Proton Pump Inhibitors for Gastroprotection in Anticoagulated Patients: A Real-World Cohort Study

Introduction Oral anticoagulation is associated with an increased risk of GI bleeding. Proton pump inhibitors (PPIs) are commonly used for gastroprotection but have pharmacologic limitations. This study examined whether vonoprazan is associated with different one-year bleeding and clinical outcomes compared with PPIs among anticoagulated adults. Methods We conducted a retrospective cohort study using the TriNetX database to identify adults receiving oral anticoagulants who initiated vonoprazan or a PPI between 2015 and 2025. Propensity score matching (1:1) was performed to balance demographics, comorbidities, procedures, concomitant medications, and baseline laboratory values. Outcomes were assessed one year after treatment initiation. The primary outcome was GI bleeding; secondary outcomes included all-cause mortality, blood transfusion, and hemoglobin level. Results After matching, 3,107 patients were included in each group. GI bleeding was lower with vonoprazan than with PPIs (55 (1.96%) vs 88 (3.18%); OR 0.61; 95% CI 0.43-0.86). All-cause mortality (177 (5.70%) vs 290 (9.38%); OR 0.58; 95% CI 0.48-0.71) and blood transfusion (≤10 (0.33%) vs 27 (0.88%); OR 0.37; 95% CI 0.18-0.76) were also lower with vonoprazan. Mean hemoglobin at one year was modestly higher with vonoprazan (11.76 ± 2.13 vs 11.54 ± 2.34 g/dL). Conclusions In a propensity-matched real-world anticoagulated cohort, vonoprazan use was associated with lower one-year GI bleeding and transfusion rates, with modestly higher hemoglobin levels, compared with PPIs. These findings are hypothesis-generating and warrant confirmation in prospective studies.