Recommendations for the safe use of direct oral anticoagulants in patients with cirrhosis based on a systematic review of pharmacokinetic, pharmacodynamic and safety data

Maaike M.E. Diesveld, Daniëlle W.M.Jacobs Pijnenburg, Rianne A. Weersink, Ina Barzel, Joost P.H. Drenth, Ton Lisman, Herold J. Metselaar, Margje H. Monster-Simons, Midas B. Mulder, Eline Okel, Katja Taxis, Sander D. Borgsteede*

*Corresponding author for this work

Research output: Contribution to journalReview articleAcademicpeer-review

Abstract

Purpose: The popularity of direct oral anticoagulants (DOACs) is increasing among patients with cirrhosis. Cirrhosis has a major impact on the pharmacokinetics of drugs, potentially increasing adverse events. Safe use of drugs in cirrhosis requires a diligent risk-benefit analysis. The aim of this study is to develop practice recommendations for safe use of DOACs in cirrhosis based on a systematic review of pharmacokinetic, pharmacodynamic and safety data. Methods: We conducted a systematic literature search to identify studies on pharmacokinetics, pharmacodynamics and safety of DOACs in cirrhosis. Data were collected and presented in summary tables by severity of cirrhosis using the Child–Turcotte–Pugh (CTP) classification. A multidisciplinary expert panel evaluated the results and classified the DOACs according to safety. Results: Fifty four studies were included. All DOACs were classified as ‘no additional risks known’ for CTP A. For CTP B, apixaban, dabigatran and edoxaban were classified as ‘no additional risks known’. Apixaban and edoxaban showed fewer adverse events in patients with cirrhosis, while dabigatran may be less impacted by severity of cirrhosis based on its pharmacokinetic profile. Rivaroxaban was classified as ‘unsafe’ in CTP B and C based on significant pharmacokinetic alterations. Due to lack of data, apixaban, dabigatran and edoxaban were classified as ‘unknown’ for CTP C. Conclusion: DOACs can be used in patients with CTP A cirrhosis, and apixaban, dabigatran and edoxaban can also be used in CTP B. It is recommended to avoid rivaroxaban in CTP B and C. There is insufficient evidence to support safe use of other DOACs in CTP C cirrhosis.

Original languageEnglish
Pages (from-to)797-812
Number of pages16
JournalEuropean Journal of Clinical Pharmacology
Volume80
Issue number6
DOIs
Publication statusPublished - Jun 2024

Bibliographical note

Publisher Copyright:
© The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature 2024.

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