Unlike warfarin direct oral anticoagulants (DOACs) are administered in fixed doses, which raises concerns of its effectiveness on larger patients. Data from randomized trials are limited on the safety and efficacy of DOACs in morbidly obese individuals with atrial fibrillation (AF).

We analyzed a cohort of obese (≥ 120 kg) and morbidly obese (BMI > 40 kg/m²) patients from the Veterans Health Administration system with AF who initiated apixaban, rivaroxaban, dabigatran, or warfarin between years 2012 and 2018. We used inverse probability of treatment weighting (IPTW) and Cox proportional hazards regression models to evaluate the relative hazard of death, myocardial infarction (MI), ischemic stroke, heart failure (HF), and bleeding events between oral anticoagulant (OAC) groups while censoring for medication cessation.

We identified 6052 obese patients on apixaban, 4233 on dabigatran, 4309 on rivaroxaban, and 13,417 on warfarin (mean age 66.7 years, 91% males, 80.4% whites). At baseline patients on apixaban had the lowest glomerular filtration rate and highest rates of previous stroke and MI compared to other OACs. Among patients with weight ≥ 120 kg and those with BMI > 40 kg/m², all DOACs were associated with lower risk of any hemorrhage, hemorrhagic stroke, and gastrointestinal (GI) bleeding. Patients with BMI > 40 kg/m² treated with DOACs had similar ischemic stroke risk with those on warfarin.

In this large cohort of obese Veterans Health Administration system patients, the use of DOACs resulted in lower hemorrhagic complications than warfarin while maintaining efficacy on ischemic stroke prevention.