Inappropriate Dosing of Direct Oral Anticoagulants in Patients with Atrial Fibrillation

Direct Oral Anticoagulants (DOACs) require dose adjustment based on specific patient characteristics, making them prone to incorrect dosing. The current study aimed to evaluate the prevalence of inappropriate DOAC dosing, its predictors, and corresponding outcomes in a single-center cohort of atrial fibrillation (AF) patients. We reviewed all patients with AF treated at Mayo Clinic with a DOAC (Apixaban, Rivaroxaban, or Dabigatran) between 2010 and 2017. Outcomes examined were ischemic stroke /transient ischemic attack (TIA)/embolism and bleeding. 8,576 patients (mean age 69.5 ± 11.9 years, 35.1 % female, CHA₂DS₂-VASc 3.0±1.8) received a DOAC (38.6% apixaban, 35.8% rivaroxaban, 25.6% dabigatran). DOAC dosing was inappropriate in 1,273 (14.8%) with 1071 (12.4%) receiving an inappropriately low dose, and 202(2.4%) an inappropriately high dose. Patients prescribed inappropriate doses were older (72.4 ± 11.7 vs 69.0 ± 11.8, p <0.0001), more likely to be female (43.1% vs 33.7%, p <0.0001), had a higher CHA₂DS₂-VASc score (3.4 ± 1.8 vs 2.9 ± 1.8, p <0.0001) and a greater Charlson co-morbidity index (3.5 ± 3.3 vs 2.9 ± 3.2, p<0.0001). Over 1.2 ±1.6 years (median 0.5 years) follow up; there was no significant difference in the incidence of stroke and/or TIA and/or embolism and bleeding between patients who were inappropriately dosed versus appropriately dosed. In conclusion, DOAC dosing was not in compliance with current recommendations in 15% of AF patients. Patients at higher risk of stroke and/or TIA based on older age, female gender, and higher CHA₂DS₂-VASc score were more likely to be underdosed, but there was no significant difference in outcomes including stroke/TIA/embolism and bleeding.