Oral anticoagulants and gastrointestinal bleeding: pharmacovigilance insights from the FDA adverse event reporting system database

BACKGROUND: There remains controversy regarding the gastrointestinal bleeding (GIB) risk associated with oral anticoagulants (OACs). This retrospective, pharmacovigilance study aimed to systematically assess the risk of OAC-associated GIB. METHODS: Disproportionality analysis was used for signal detection and subgroup analysis, and multivariable logistic regression was performed based on age, sex, weight, comorbidity, indication, and concomitant drugs. Stratification analysis was further conducted according to GIB location (lower GIB, upper GIB, and unspecified sites). RESULTS: A total of 24 421 OAC-associated GIB identified in the FDA adverse event reporting system database, from 2008 Q1 to 2025 Q1. Significant signal of GIB risk was identified in OACs (ROR: 16.56, 95% CI: 16.34-16.79, IC025: 3.59), with consistent results across different GIB locations. Direct oral anticoagulants (DOACs) exhibited a lower GIB risk compared to vitamin K antagonists (VKAs); notably, dabigatran demonstrated a heightened risk of lower GIB compared to other OACs. The most prominent signals included hemorrhagic gastroenteritis with edoxaban (IC025: 7.03), intestinal hematoma with VKAs (IC025: 6.34), lower gastrointestinal hemorrhage with dabigatran (IC025: 5.02), gastrointestinal hemorrhage with rivaroxaban (IC025: 4.27), and anal ulcer hemorrhage (IC025: 4.22) with apixaban. Most cases occurred in patients older than 75 years within first 3 months of treatment. CONCLUSION: DOACs showed a significantly lower risk of GIB than VKAs, though dabigatran exhibited a higher risk of lower GIB compared to other OACs. Different OACs exhibited distinct risk profiles across GIB locations, providing critical insights for optimizing anticoagulation management strategies.