Efficacy and Safety of Direct Oral Anticoagulants for Atrial Fibrillation Across Body Mass Index Categories

Background Direct-acting oral anticoagulants are now the preferred method of anticoagulation in patients with atrial fibrillation. Limited data on efficacy and safety of these fixed-dose regimens are available in severe obesity where drug pharmacokinetics and pharmacodynamics may be altered. The objectives of this study were to evaluate efficacy and safety in patients with atrial fibrillation taking direct-acting oral anticoagulants across body mass index (BMI) categories in a contemporary, real-world population. Methods and Results We performed a retrospective study of patients with atrial fibrillation at an integrated multisite healthcare system. Patients receiving a direct-acting oral anticoagulant prescription and ≥12 months of follow-up between 2010 and 2017 were included. The primary efficacy and safety outcomes were ischemic stroke or systemic embolism and intracranial hemorrhage. We performed Cox proportional hazards modeling to compute hazard ratios (HRs) adjusted for CHA₂DS₂-VASc score to examine differences by excess BMI categories relative to normal BMI. Of 7642 patients, mean±SD age was 69±12 years with a median (interquartile range) follow-up of 3.8 (2.2-6.0) years. Approximately 22% had class 1 obesity and 19% had class 2 or 3 obesity. Stroke risks were similar in patients with and without obesity (HR, 1.2; 95% CI, 0.5-2.9; and HR, 0.68; 95% CI, 0.23-2.0 for class 1 and class 2 or 3 obesity compared with normal BMI, respectively). Risk of intracranial hemorrhage was also similar in class 1 and class 2 or 3 obesity compared with normal BMI (HR, 0.64; 95% CI, 0.35-1.2; and HR, 0.66; 95% CI, 0.35-1.2, respectively). Conclusions Direct-acting oral anticoagulants demonstrated similar efficacy and safety across all BMI categories, even at high weight values.