Thrombotic Versus Hemorrhagic Risk: Critical Decision-Making in Nonvariceal Upper Gastrointestinal Bleeding

Acute non-variceal upper gastrointestinal bleeding (NVUGIB) in patients receiving antithrombotic therapy requires bleeding control to be balanced against the thromboembolic consequences of treatment interruption or reversal. This narrative review summarizes recent gastroenterology, cardiology, and hemostasis guidance, including the 2026 European Society of Gastrointestinal Endoscopy (ESGE) update on peptic ulcer bleeding, the 2022 American College of Gastroenterology–Canadian Association of Gastroenterology guideline, recent European Society of Cardiology and American College of Cardiology/American Heart Association guidelines, and current evidence and regulatory positions on anticoagulant reversal. Endoscopic recommendations are presented as applying to peptic ulcer bleeding, from which they were derived; variceal bleeding is outside the scope of the review. The review addresses risk stratification, resuscitation, endoscopic hemostasis, management of antiplatelet and anticoagulant therapy during acute bleeding, reversal, and resumption of therapy, with separate consideration of atrial fibrillation, recent acute coronary syndrome or percutaneous coronary intervention, chronic coronary and peripheral arterial disease, mechanical valves, and frail older patients. Principal studies are reported with effect estimates and 95% confidence intervals where available, and guideline recommendations are distinguished from the authors’ proposed approach. Current evidence supports timely hemostasis, avoidance of unnecessary interruption, selective rather than routine reversal, and individualized resumption when the indication persists, although evidence on reversal-agent choice and restart timing is largely observational and of low certainty. Seven practical principles, representing the authors’ synthesis rather than formal recommendations, are proposed.