BackgroundThe optimal dose of direct oral anticoagulants (DOACs) to prevent ischemic stroke (IS) and systemic thromboembolism (STE) in atrial fibrillation (AF) patients with a predisposing bleeding risk remains unclear. ObjectiveThe purpose of this study was to compare the effectiveness and safety of different DOAC dosage regimens in AF patients with high bleeding risk but low thrombosis risk. MethodsThis retrospective observational study was conducted with the National Health Insurance claims database in Taiwan to include AF patients aged 20 up to 75 years, under DOAC therapy, with CHA2DS2-VASc score of 1 for males and 2 for females and HAS-BLED score ≥3. Standard-dose regimen was defined as dabigatran 300 mg, rivaroxaban 20 mg, apixaban 10 mg, or edoxaban 60 mg per day. Any other lower-dose regimen were defined as the low-dose regimen. The primary outcomes were IS and major bleeding (MB). The secondary outcomes were STE, gastrointestinal bleeding, intracranial hemorrhage, and cardiovascular death. ResultsA total of 964 patients were included (52.1% standard-dose regimen). Median HAS-BLED score was 3 [interquartile range 3–3]. Compared with standard-dose group, patients in the low-dose group had a significantly increased risk of IS (adjusted hazard ratio [aHR] 5.13; 95% confidence interval 1.37–19.22) and STE (aHR 3.14 [1.05–9.37]) but similar risk of MB (aHR 0.45 [0.12–1.67]). The risks of other hemorrhage and cardiovascular death were similar between the 2 dose groups. ConclusionAmong patients with a predominant bleeding risk but relatively low thrombosis risk, the low-dose DOAC regimen is not a more appropriate selection than standard-dose regimen.