Direct Oral Anticoagulant Concentrations in Obese and High Body Weight Patients: A Cohort Study

Abstract

Background Direct oral anticoagulants (DOACs) are prescribed for atrial fibrillation (AF) and venous thromboembolism (VTE) and both occur more frequently in obese patients. Outcomes from DOAC trials included few individuals ≥ 120 kg leading to uncertainty whether high body weight (BW) reduces DOAC concentrations.

Objectives This article investigates the relationship between factor Xa (FXa) inhibitor concentrations, BW, and renal function, and compares them in high BW patients with unselected populations.

Methods Consecutive patients in two United Kingdom centers, weighing ≥ 120 kg receiving 5 mg twice daily apixaban or 20 mg once daily rivaroxaban for AF or VTE were prospectively included. Peak or trough concentrations were measured using specific chromogenic assays, 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.

Results One hundred patients were included; age range: 23 to 78 years, 31% were women, 58% had AF, creatinine clearance range: 67 to 474 mL/min. Median BW was 139 kg, and 84% had body mass index (BMI) ≥ 40 kg/m². DOAC peak and trough concentrations varied from 44 to 727 and 14 to 299 ng/mL, respectively. There was no linear relationship between FXa inhibitor concentrations at peak or trough and BW or BMI, and creatinine clearance. Apixaban troughs in AF and rivaroxaban peaks in VTE were lower than in unselected populations. However, only two trough concentrations were below the expected range, and 109/116 were within the on-therapy range.

Conclusion These data indicated that obese or high BW patients generally achieve therapeutic FXa inhibitor concentrations. However, further investigations assessing clinical outcomes are required.

Keywords

direct oral anticoagulants - high body weight and obesity - atrial fibrillation - venous thromboembolism - drug concentrations

Authors' Contributions

A.-C.M. designed and performed research, analyzed data, and wrote the manuscript. W.T. designed and performed the research and wrote the manuscript. Z.M. performed research and reviewed and revised the manuscript. M.P.C. performed research and reviewed and revised the manuscript. T.D. performed research and reviewed and revised the manuscript. K.B. performed research and reviewed and revised the manuscript. V.C. performed research and reviewed and revised the manuscript. G.W.M. and S.M.D. coordinated the sample swap and ran the samples for the analysis. G.W.M. and S.M.D. also appraised the manuscript while it was being written and provided feedback and approval. B.H. performed research and reviewed and revised the manuscript. A.T.C. designed and performed the research, analyzed the data, and wrote the manuscript. All authors performed the research, contributed to the manuscript, reviewed the manuscript while it was being written, provided feedback, and gave final approval.

Publication History

Received: 19 June 2020

Accepted: 21 July 2020

Article published online:
30 August 2020

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