Abstract Body (Do not enter title and authors here): Background: Direct oral anticoagulants (DOACs) are recommended for stroke prevention in patients with atrial fibrillation (AF); however, inappropriate dosages may increase risk for adverse events. Using data from the American Heart Association’s Get with the Guidelines-Stroke registry (GWTG-Stroke) linked with Medicare data, we evaluated the association of DOAC dosing with risk of stroke/systemic embolism, major bleeding, and all-cause mortality in older ischemic stroke patients with AF.

Methods: We included ischemic stroke patients admitted to a GWTG-Stroke hospitals in Oct. 2012-Dec. 2019 who were >66 years, had a history of AF/flutter, and were discharged on a DOAC (dabigatran, rivaroxaban, or apixaban). DOAC dosing was defined as appropriate (standard dose or appropriately adjusted dose), underdose (reduced dose without indications for dose reduction or dose lower than recommended), or overdose (standard dose in patients with indications for dose reduction or dose higher than recommended). Normalized inverse probability weighted generalized boosted models were used to estimate 1-year outcomes after discharge.

Results: Of the 37,464 ischemic stroke survivors (median age: 81 years; 53% female; 7% non-Hispanic Black), 68% were discharged with the appropriate DOAC dose, 22% were underdosed and 10% were overdosed. Apixaban was the most common DOAC (68%), followed by rivaroxaban (23%) and dabigatran (9%). The cumulative 1-year incidence of stroke/systemic embolism were 7.1%, 7.0%, and 7.9% among patients who were appropriate dosed, underdosed, and overdosed. After multivariable adjustments, there was no significant association between DOAC dose and stroke/systemic embolism (Table). However, patients who were overdosed (aHR 1.11 [1.01-1.23]) were associated with greater risk of major bleeding compared with appropriately dosed patients. Furthermore, patients who were underdosed were associated with greater risk of all-cause mortality (aHR 1.12 [1.06-1.18]). No significant association with mortality risk was observed in those who were overdosed.

Conclusion: In a nationwide registry of ischemic stroke survivors with AF, approximately one-third of patients were prescribed a non-recommended DOAC dose. Patients who were overdosed had greater risk of major bleeding, while those underdosed had a greater risk of all-cause mortality. Strategies, including medical education, to ensure appropriate DOAC dosing at discharge are needed to reduce risk of adverse outcomes.