2025 Southeastern Residency Conference

Title: Direct oral anticoagulants and potential inconsistencies with recommended dosing in atrial fibrillation


Authors: Kelsey Maynard, Melissa Johnson, David Cruse, Cody Veal, Chelsea Keedy


Background: Direct oral anticoagulants are commonly recommended in atrial fibrillation patients to prevent thromboembolism. Anticoagulant dosing not aligned with approved labeling has been associated with increased risk of cardiac hospitalization, stroke, all-cause mortality, and bleeding. Previous studies have reported 20 to 32 percent of atrial fibrillation patients have their direct oral anticoagulants dosed outside labeling recommendations. The objectives of this study were to determine the rate of direct oral anticoagulant dosing that is outside of approved labeling for patients with atrial fibrillation at three outpatient primary care clinics of a community health system and determine the characteristics of those inappropriately dosed.


Methods: This was a retrospective, cross-sectional analysis evaluating adult patients diagnosed with atrial fibrillation treated with direct oral anticoagulants from January 1^st, 2023 to December 31^st, 2023. Patients were excluded if they were less than 18 years old or greater than 89 years old, pregnant or experienced childbirth within study period, or if they had been previously diagnosed with a clotting disorder.  Patients were also excluded if they were treated for venous thromboembolism, hip/knee replacement, left ventricular thrombus or heparin induced thrombocytopenia during the study period. The primary outcome is to determine the percentage of atrial fibrillation patients with direct oral anticoagulant dosing that is not consistent with the Food and Drug Administration approved labeling. Secondary analyses were completed to determine the percentage of atrial fibrillation patients with particular clinical or demographic characteristics who were inappropriately dosed. Characteristics evaluated included age, sex, race, drug name, drug dose, drug dosing instructions, body weight, serum creatinine, concomitant CYP450/PGP drug-drug interactions, concomitant medications, hemodialysis status, primary care office location, prescriber, social deprivation index, CHA₂DS₂-VASc, HAS-BLED, and history of bleeding.


Results: Two hundred and twenty-two patients met inclusion criteria for analysis. Thirty-six of these patients had their direct oral anticoagulant inappropriately dosed (16.2%). Of the inappropriately dosed patients, the average age was 81 years old, 20 patients were female (55.6%), 29 were Caucasian (80.6%), 2 patients were on dialysis (5.6%), and 11 patients had a history of bleeding (30.6%). Twenty-five patients were prescribed apixaban (69.4%) and 11 patients were prescribed rivaroxaban (30.6%). Ten of these patients (27.8%) had their direct oral anticoagulant prescribed by their primary care provider, the average CHA₂DS₂-VASc score was 3.5, and the average HAS-BLED score was 2.1. Eight patients (22.2%) were also prescribed a CYP450/PGP medication and 16 patients (44.4%) were also prescribed a nonsteroidal inflammatory drug, glucocorticoid, antiplatelet, or selective serotonin reuptake inhibitor. Nineteen of the inappropriately dosed patients (52.8%) had their direct oral anticoagulant under dosed, nine patients (25%) did not have their direct oral anticoagulant adjusted for their creatinine clearance appropriately, six patients (16.7%) met two of the three dose adjustment criteria for apixaban dose adjustment, and two patients (5.6%) were on dialysis and were not greater than 80 years old or less than 60 kg.


Conclusion: The majority of the atrial fibrillation patients in three of our community health system’s outpatient primary care clinics have their direct oral anticoagulants dosed appropriately per the Food and Drug Administration’s approved dosing. The atrial fibrillation patients in our primary care clinics at highest risk of having their direct oral anticoagulants inappropriately dosed are patients who are elderly, female, Caucasian, and prescribed apixaban. These patients are more often under dosed.