Comparison of different direct oral anticoagulant regimens in atrial fibrillation patients with high bleeding risk

Abstract

Background: The 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.

Objective: The 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.

Methods: This 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.

Results: A 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.

Conclusion: Among 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.

Keywords: Atrial fibrillation; Comparative effectiveness and safety; Direct oral anticoagulants; Dose regimens; High bleeding risk; Moderate thrombosis risk.