Proton pump inhibitors (PPIs) can reduce the risk of upper gastrointestinal bleeding (UGIB) in patients who are taking oral anticoagulants. This study aimed to identify the association between NOACs with PPI cotherapy and UGIB. This retrospective cohort analysis included patients over the age of 18 years who were using NOACs between 2013 and 2020. NOAC categories, concomitant medications, endoscopic findings, the HAS-BLED score and the Charlson Comorbidity Index score were recorded. Using Poisson regression models, the relationship between UGIB events and risk factors was analyzed. Throughout a mean follow-up of 29.5 months, 14 (5.1%) individuals experienced UGIB. The incidence of UGIB was greater in patients receiving NOACs without PPIs (2.7 [1.26-5.60] per 1000) than in those receiving NOACs with PPIs (1.3 [0.61-2.67] per 1000). Patients receiving NOACs with PPIs had a 79.2% lower incidence of UGIB than patients receiving NOAC monotherapy (RR 0.208, 95% CI 0.061-0.706; p = 0.012). Female sex and the HAS-BLED score were associated with UGIB (RR 5.043; 95% CI 1.096-23.20; p = 0.038; RR 2.024; 95% CI 1.095-3.743; p = 0.024, respectively). Patients receiving NOAC and PPI cotherapy had a lower incidence of UGIB than those receiving NOACs alone, and female sex was a risk factor for UGIB in NOAC-treated patients.
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