Characteristics of Gastrointestinal Bleeding While Taking Direct Oral Anticoagulants in Patients with Nonvalvular Atrial Fibrillation and Differences Among Drugs-A Single-Center Retrospective Cohort Study

Introduction: Direct oral anticoagulants (DOACs) are frequently used to prevent embolism in atrial fibrillation. Gastrointestinal bleeding is frequent, but its drug-specific characteristics remain unclear. This study examined the frequency and characteristics of gastrointestinal bleeding in patients with nonvalvular atrial fibrillation for different DOACs. Methods: The present study included 978 patients receiving treatment with DOACs for nonvalvular atrial fibrillation between 2011 and 2018 and examined the frequencies of clinically significant events including major cardiovascular and cerebrovascular events, hemorrhagic events, or death during the first 5 years of prescription. Gastrointestinal bleeding was evaluated for the frequency, source and severity of gastrointestinal bleeding by DOAC type. Results: The median age of subjects was 73 years (interquartile range, 65-80 years), and 622 (64%) were male. The overall observation period was 2499 person-years. During this period, 102 (4.1/100 person-years) major cardiovascular events and 107 (4.3/100 person-years) clinically significant bleeding were reported, including 60 cases (2.4/100 person-years) of gastrointestinal bleeding and 37 cases (1.5/100 person-years) of all-cause mortality. Gastrointestinal bleeding accounted for more than half of all bleeding events among DOAC users, and bleeding from the lower gastrointestinal tract was more common than that from the upper gastrointestinal tract, particularly with dabigatran. No significant difference was seen in the rate of gastrointestinal bleeding by drug type. Peptic ulcer accounted for half of the events of upper gastrointestinal bleeding, all of which were severe. Conclusions: Gastrointestinal bleeding is frequent among patients taking DOACs, especially from the lower alimentary tract. The tendency was more pronounced with dabigatran. In the upper gastrointestinal tract, severe peptic ulcer bleeding is common and requires caution.