Patients with higher body mass index treated with direct / novel oral anticoagulants (DOAC / NOAC) for atrial fibrillation experience worse clinical outcomes

Abstract

Introduction: Due to fixed dosing of direct oral anticoagulants (DOACs), uncertainty exists about their efficacy in a population of obese/overweight patients.

Patients and methods: We retrospectively investigated a real-life cohort of 325 DOAC anticoagulated patients with atrial fibrillation [179 receiving dabigatran (55%), 74 apixaban (23%) and 72 rivaroxaban (22%)]. Patients were stratified according to the body mass index (BMI) into non-obese (233 with BMI <30 kg/m²), class I obesity (71 with BMI 30-34.9 kg/m²) and class II + obesity (21 with BMI ≥35 kg/m²).

Results: Patients with higher BMI receiving DOACs were more likely to experience stroke/systemic embolism sooner (P = 0.043), experience major bleeding sooner (P < 0.001) and have shorter time to composite event consisting of thrombosis, bleeding or death (P < 0.001) whereas there was no significant association with overall survival (P = 0.470). BMI was significantly associated with thrombosis but not bleeding among dabigatran treated patients, and significantly associated with bleeding but not thrombosis among patients treated with factor Xa inhibitors. Associations of higher thrombotic, bleeding and composite endpoint risks with higher BMI remained statistically significant in multivariate Cox regression models adjusted for age, gender, eGFR, CHA₂DS₂VASC and HAS-BLED.

Conclusion: Our findings indicate that obese patients receiving DOACs, especially ones with class II + obesity, might be under higher risks of stroke/bleeding depending on DOAC subtype. Loss of efficacy might be associated with dabigatran, whereas higher risk of major bleeding might be associated with factor Xa inhibitors.

Keywords: Atrial fibrillation; Bleeding; Body mass index; Direct oral anticoagulants; Obesity; Thrombosis.