Direct oral anticoagulant plasma concentrations in obese and high body weight patients: An observational study

Abstract

Direct oral anticoagulants (DOAC) are prescribed for atrial fibrillation (AF) and venous thromboembolism (VTE) and both occur more frequently in obese patients. However, outcomes from DOAC trials included few individuals ≥ 120 kg, and there is uncertainty whether high body weight reduces DOAC concentrations. We investigated the relationship between factor Xa (FXa) inhibitor concentrations, body weight, and renal function, and compared them in high body weight patients with those published for unselected populations. Consecutive patients in two UK centres, weighing ≥ 120 kg receiving 5 mg bid apixaban or 20 mg od rivaroxaban for AF or VTE were prospectively included. Peak or trough concentrations were measured using specific chromogenic assays and expressed in mean or median (5th-95th percentiles). On-therapy range was the interval from the 5th percentile trough concentration to the 95th percentile peak concentration. One hundred patients were included; age range: 23-78, 31% were women, 58% had AF, creatinine clearance range: 67-474 mL/min. Median body weight was 139 kg, and 84% had BMI ≥ 40 kg/m 2 . DOAC peak and trough concentrations varied from 44 to 727 ng/mL and 14 to 299 ng/mL, respectively. There was no linear relationship between FXa inhibitor concentrations at peak or trough and body weight or body mass index, and creatinine clearance. Apixaban troughs in AF and rivaroxaban peaks in VTE were lower than in unselected populations. However, only 2 trough concentrations were below the expected range, and 109/116 were within the on-therapy range ( Fig. 1 ). These data indicate that obese or high body weight patients generally achieve therapeutic concentrations and hence therapeutic options should not be limited in these patients.