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CC BY 4.0 · TH Open 2024; 08(01): e31-e41
DOI: 10.1055/s-0043-1776989
Review Article

Direct-Acting Oral Anticoagulants in patients at extremes of body weight: a review of pharmacological considerations and clinical implications

Rosa Talerico 
1   Section of Internal Medicine and Thromboembolic Diseases, Department of Internal Medicine, Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica del Sacro Cuore, Rome, Italy
2   IRCCS San Raffaele, Rome, Italy
,
Roberto Pola 
1   Section of Internal Medicine and Thromboembolic Diseases, Department of Internal Medicine, Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica del Sacro Cuore, Rome, Italy
,
Frederikus Albertus Klok 
3   Department of Medicine—Thrombosis and Hemostasis, Leiden University Medical Center, Leiden, The Netherlands.
,
Menno Volkert Huisman
3   Department of Medicine—Thrombosis and Hemostasis, Leiden University Medical Center, Leiden, The Netherlands.
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Abstract

Patients at extremes of body weight are underrepresented in randomized controlled trials of direct-acting oral anticoagulants (DOACs). Therefore, their optimal anticoagulant treatment remains a topic of debate.

The aim of this narrative review is to summarize the evidence on the pharmacokinetic and pharmacodynamic profile of DOACs for treating patients at extremes of body weight in venous thromboembolism (VTE) and in the prevention of cardioembolic stroke in nonvalvular atrial fibrillation (NVAF). A literature search was conducted in the main bibliographic databases, and the most relevant reviews and original articles on the topic were selected.

Although data in these patient groups are limited, apixaban and rivaroxaban show a favorable pharmacokinetic and pharmacodynamic profile in obese VTE treatment and NVAF patients and, in the case of apixaban, also in underweight patients. In particular, these drugs demonstrated comparable efficacy and safety to standard therapy. Very few data were available for dabigatran and edoxaban; the latter drug was safer at a lower dose, mainly in underweight patients.

Our findings are in line with the last International Society of Haemostasis and Thrombosis position paper and European Heart Rhythm Association 2021 practical guide, suggesting the use of apixaban and rivaroxaban in morbidly obese patients (>120 kg or body mass index ≥40 kg/m2) and the reduced dosage of edoxaban in low-weight patients. Future studies should focus on large populations of patients at extremes of body weights to acquire more clinical and pharmacokinetic evidence on all available DOACs, especially those currently less investigated.

Keywords

direct-acting oral anticoagulants - obese - underweight - extremes of body weight - pharmacokinetics


Publication History

Received: 28 July 2023

Accepted: 16 October 2023

Article published online:
08 January 2024

© 2024. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/)

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