Supplementary Material for: Underdosed Direct Oral Anticoagulants in Atrial Fibrillation Patients Reduce Stroke Severity and Improve Outcome

Background and Purpose: Anticoagulant drugs, including vitamin K antagonist (VKA) and direct oral anticoagulants (DOACs), can reduce stroke severity and are associated with good functional outcomes. Some patients are prescribed lower-than-recommended doses of DOACs; whether these have similar effects has not been clarified. Methods: We retrospectively evaluated 1,139 consecutive ischemic stroke and transient ischemic attack patients with atrial fibrillation. Patients were divided into 5 groups according to their preceding anticoagulant drug therapies: no anticoagulant therapy (ACn), undercontrolling VKA doses (VKAuc), recommended, controlling VKA doses (VKArec), prescribed underdoses of DOAC (DOACud), and recommended doses of DOAC (DOACrec). We investigated the associations between these anticoagulant drug therapies and patients’ initial stroke severity and 3-month outcomes. Results: Median National Institutes of Health Stroke Scale scores at admission were as follows: ACn: 16, VKAuc: 15, VKArec: 9, DOACud: 5, and DOACrec: 7. When the ACn group was used as a reference, regression analysis showed that VKArec (odds ratio [OR] 1.49, 95% confidence interval [CI] 1.01–2.21), DOACud (OR 2.84, 95% CI: 1.47–5.66), and DOACrec (OR 1.83, 95% CI: 1.23–2.74) were associated with milder stroke severity, while VKAuc was not. Median 3-month modified Rankin Scale scores were 2 in the DOACud and DOACrec groups and 4 in all other groups. After adjusting for confounding factors, DOACud (OR 3.14, 95% CI: 1.50–6.57) and DOACrec (OR 1.67, 95% CI: 1.05–2.64) were associated with good 3-month outcomes while VKAuc and VKArec were not. Conclusions: In patients with atrial fibrillation, recommended doses and underdoses of DOACs reduced stroke severity on admission and were associated with good 3-month outcomes.