The influence of extremely high body weight (BMI > 35kg/ m2) on apixaban plasma concentration in patients with atrial fibrillation

Abstract Apixaban, a direct oral anticoagulant (DOAC) is administered in a fixed-dose regimen for atrial fibrillation patients. Dosage adjustment is based on renal function, age, and body weight (less than 60 kg). No data exist on the pharmacokinetics of apixaban in patients with body mass index (BMI) ≥ 35 Kg/m2, nor about treatment efficacy and safety in this population. Aims: To reveal whether BMI ≥ 35 kg/m2 affects trough plasma concentrations of apixaban in patients with atrial fibrillation and whether dose adjustment is required in this population. Methods: This prospective study compared steady state trough concentrations of apixaban in patients with BMI ≥ 35 kg/m2 and patients with BMI < 35 kg/m2. Results: Sixty patients were included in the study. In patients on 5 mg twice daily dose, the median trough plasma concentration was 29% lower in the high BMI group (BMI ≥ 35 kg/m2) compared with the lower BMI group (BMI < 35 kg/m2) (148.9 ng/ml, IQR: 94.5-205.6, compared to 209.1 ng/ml IQR: 167- 266.8 ng/ml respectively). P = 0.044. However, median trough concentrations were within the manufactures predicted steady-state apixaban exposure range. A similar trend was found among patients treated with 2.5 mg apixaban twice daily, but the results did not reach statistical significance. According to multivariate analysis performed, no correlation was found between BMI values (neither BMI ≥ 35 kg/m2 nor BMI < 35 kg/m2) and trough concentrations. Conclusion: Lower apixaban trough concentration was observed in patients with BMI ≥ 35 kg/m2 but remains within the steady-state apixaban exposure range found to be effective according to manufacturer data.