Abstract Number: PB2389
Meeting: ISTH 2020 Congress
Background: To date, there has been no data from clinical practice to suggest that pharmacokinetic (PK) parameters are not substantially altered at the extremes of bodyweight. The International Society of Thrombosis and Haemostasis Scientific and Standardisation Committee (ISTH SSC) suggest avoiding direct oral anticoagulants (DOACs) in patients weighing >120kg or BMI >40kg/m2 and give no recommendation in those < 50kg. Emerging safety and efficacy data for rivaroxaban in morbid obesity suggests traditional therapy and rivaroxaban are comparable.
Aims: To develop a population PK model to understand the influence of bodyweight on rivaroxaban exposure.
Methods: Between 2013 and 2018, rivaroxaban plasma concentrations, laboratory markers and patient characteristics were collated from patients prescribed rivaroxaban attending the anticoagulation clinics at KCH. Patients were eligible if a time of last rivaroxaban dose was recorded. A population PK model was developed using a non-linear mixed effects approach, and then used to simulate rivaroxaban concentrations in patient subgroups of interest such as extremes of bodyweight and stages of renal impairment.
Results: A population PK model was developed from 913 patients weighing between 39kg and 172kg (table 1). Notably, 86 patients weighed >120kg, 74 patients had a BMI >40kg/m2, and 30 patients weighed < 50kg.
|Patient characteristics||N = 913|
|Gender, male (%)||522 (57.2)|
|Age, years (mean [range])||67 [19 – 96]|
|Weight, (kg) (mean [range])||85.8 [39.0 – 171.6]|
|BMI, kg/m2 mean [range])||29.7 [15.6 – 55.8]|
|CRCL, ml/min (mean [range])||91.5 [15.9 – 297.2]|
|Indication for anticoagulation (%)||AF = 629 (68.9)|
|VTE = 267 (29.2)|
|Other = 17 (1.9)|
|Abbreviations: AF, atrial fibrillation; BMI, body mass index; CRCL, creatinine clearance calculated using total bodyweight; VTE, venous thromboembolism *Other indications for anticoagulation – Left ventricular thrombus, cardioembolic stroke of unknown aetiology|
[Table 1. Patient characteristics and indications for anticoagulation]
A one compartment-model with between subject variability on apparent clearance and a proportional error model best described the data. Creatinine clearance, calculated using Cockcroft Gault with lean bodyweight as the weight descriptor in the equation, was the most significant covariate influencing rivaroxaban exposure (figure 1).
Conclusions: Our work suggests that if renal function is adequate then rivaroxaban can be prescribed at the extremes of bodyweight. Current guidance with respect to rivaroxaban should be revised, recommending it as a suitable option for patients with a BMI >40kg/m2 or weight >120kg, and those < 50kg. Further research is required to establish whether the same is true for other DOACs.
[Figure1. Simulation plots derived from steady state data for rivaroxaban 20mg once daily.]
To cite this abstract in AMA style:Speed V, Green B, Roberts L, Woolcombe S, Bartoli-Abdou J, Barsam S, Byrne R, Gee E, Czuprynska J, Brown A, Duffy S, Vadher B, Patel R, Scott V, Gazes A, Patel R, Arya R, Patel J. Fixed Dose Rivaroxaban Can Be Prescribed in Extremes of Bodyweight, Results of a Population Pharmacokinetic Analysis [abstract]. Res Pract Thromb Haemost. 2020; 4 (Suppl 1). https://abstracts.isth.org/abstract/fixed-dose-rivaroxaban-can-be-prescribed-in-extremes-of-bodyweight-results-of-a-population-pharmacokinetic-analysis/. Accessed December 6, 2023.
« Back to ISTH 2020 Congress
ISTH Congress Abstracts - https://abstracts.isth.org/abstract/fixed-dose-rivaroxaban-can-be-prescribed-in-extremes-of-bodyweight-results-of-a-population-pharmacokinetic-analysis/