Edoxaban, apixaban, and rivaroxaban were associated with a lower risk of ischemic stroke/systemic embolism than warfarin. All DOACs had a lower risk of major bleeding than warfarin. Apixaban was associated with a lower risk of major bleeding than rivaroxaban and
dabigatran, whereas the risk ofmajor bleeding was comparable between edoxaban and apixaban. The reduced risks of thromboembolism/major bleeding for the four DOACs persisted in highrisk subgroups, including those with chronic kidney disease, elderly patients (age $ 75 years), secondary stroke prevention, or CHA2DS2-VASc score (congestive heart failure, hypertension,
age$ 75 years, diabetesmellitus, previous stroke/transient ischemic attack, vascular disease, age Q7 65-74 years, and female sex) $ 4. A total of 2,924 (64%), 6,359 (64%), 31,108 (94%), and 19,821 (89%) patients received low-dose edoxaban (15-30 mg/d), apixaban (2.5 mg bid), rivaroxaban (10-15 mg/d), and dabigatran (110mg bid), respectively. The effectiveness/safety outcomes with
the four low-dose DOACs compared with warfarin were consistent with the main analysis.