Abstract

This study sought to evaluate direct oral anticoagulant (DOAC) outcomes (vs. warfarin) in patients with atrial fibrillation (AF) across body mass index (BMI) categories, including≥40 and<18.5kg/m2. Clinical trials have not systematically tested the fixed DOAC dosing in underweight and morbidly obese patients. We retrospectively included consecutive patients with nonvalvular AF with CHA2DS2-VASc (Congestive heart failure, Hypertension, Age ≥75, Diabetes, Stroke/transient ischemic attack/systemic thromboembolism, Vascular disease, Age 65-74, Sex) of≥1 receiving OACs at our hospital system (2010-2018). Patients were categorized into groups 1 (underweight: BMI of<18.5kg/m2), 2 (normal/overweight: BMI of 18.5 to<30kg/m2), 3 (grade 1/2 obesity: BMI of 30 to<40kg/m2), and 4 (grade 3 obesity: BMI of≥40kg/m2). We further classified patients by DOAC versus warfarin use. Outcomes were ischemic stroke, significant bleeding events (i.e., resulting in hospitalization), and mortality. We included 36,094 patients with a mean age of 74 ± 11 years and CHA2DS2-VASc of 3.4 ± 1.5. Groups 1 through 4 included 455 (1.3%), 18,339 (50.8%), 13,376 (37.1%), and 3,924 (10.9%) patients, respectively. DOAC use ranged from 49% to 56%. At 3.8 follow-up years, with multivariable Cox regression, DOACs (vs. warfarin) were associated with lower risk of ischemic stroke, bleeding, and mortality across all BMI groups, with hazard ratios (HRs) of 0.73 (95% confidence interval [CI]: 0.63 to 0.85), 0.75 (95% CI: 0.64 to 0.87), 0.75 (95% CI: 0.65 to 0.88), and 0.75 (95% CI: 0.64 to 0.87) (p<0.001 for all) for ischemic stroke; 0.42 (95% CI: 0.19 to 0.92), 0.41 (95% CI: 0.19 to 0.89), 0.45 (95% CI: 0.20 to 1.00), and 0.43 (95% CI: 0.20 to 0.94) (p<0.05 for all) for bleeding; and 0.90 (95% CI: 0.68 to 1.19; p=0.5), 0.70 (95% CI: 0.66 to 0.75; p<0.0001), 0.65 (95% CI: 0.60 to 0.71; p<0.0001), and 0.66 (95% CI: 0.56 to 0.77; p<0.0001) for mortality, in groups 1 to 4, respectively. In patients with nonvalvular AF, DOACs compared to warfarin were associated with better safety and effectiveness across all BMI categories, including underweight and morbidly obese patients.

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