Outcomes of Direct Oral Anticoagulants in Atrial Fibrillation Patients Across Different Body Mass Index Categories

Abstract

Objectives: 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 <18.5 kg/m².

Background: Clinical trials have not systematically tested the fixed DOAC dosing in underweight and morbidly obese patients.

Methods: 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 <18.5 kg/m²), 2 (normal/overweight: BMI of 18.5 to <30 kg/m²), 3 (grade 1/2 obesity: BMI of 30 to <40 kg/m²), and 4 (grade 3 obesity: BMI of ≥40 kg/m²). We further classified patients by DOAC versus warfarin use. Outcomes were ischemic stroke, significant bleeding events (i.e., resulting in hospitalization), and mortality.

Results: 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.

Conclusions: 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.

Keywords: atrial fibrillation; bleeding; obesity; oral anticoagulation; stroke; underweight.