Review Article: Gastrointestinal Bleeding Risk with Direct Oral Anticoagulants

Abstract

Purpose: Although direct oral anticoagulants (DOACs) are associated with an overall favourable safety profile, the risk of gastrointestinal bleeding with DOACs compared with vitamin K antagonists (VKAs) remains controversial. Accordingly, we aimed to provide a focused overview of the risk of gastrointestinal bleeding associated with dabigatran, rivaroxaban, apixaban and edoxaban and its management.

Methods: We reviewed published studies reporting on DOACs with gastrointestinal bleeding as an outcome, including randomised controlled trials (RCTs), retrospective database studies and large-scale prospective cohort studies.

Results: Cumulative evidence confirms no notable difference in major gastrointestinal bleeding risk between DOACs and VKAs. Moreover, gastrointestinal bleeding in DOAC-treated patients seems less severe and requires less intensive management. The main cause of upper gastrointestinal bleeding in DOAC-treated patients appears to be gastroduodenal ulcers, whereas lower gastrointestinal bleedings are mainly due to diverticula followed by angiodysplasia and haemorrhoids. The lack of head-to-head RCTs with DOACs precludes drawing conclusions on the DOAC with the lowest gastrointestinal bleeding risk. Prescribing physicians should be aware of risk factors for DOAC-related gastrointestinal bleeding (e.g. age > 65, heavy alcohol use, uncontrolled hypertension, hepatic or renal dysfunction, active cancer, anaemia) and adopt preventive measures accordingly. Management of DOAC-associated major gastrointestinal bleeding involves temporary discontinuation of the DOAC, investigation of the bleeding source and treatment of bleeding with fluid resuscitation combined with transfusion and endoscopic haemostasis.

Conclusion: DOACs as a class do not increase the risk of major gastrointestinal bleeding compared to VKAs, which supports their continued use for different anticoagulant indications.

Keywords: Apixaban; Dabigatran; Direct oral anticoagulants; Edoxaban; Gastrointestinal bleeding; Rivaroxaban.