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Challenges and Possible Solutions to Direct-Acting Oral Anticoagulants (DOACs) Dosing in Patients with Extreme Bodyweight and Renal Impairment

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Abstract

This article aims to highlight the dosing issues of direct oral anticoagulants (DOACs) in patients with renal impairment and/or obesity in an attempt to develop solutions employing advanced data-driven techniques. DOACs have become widely accepted by clinicians worldwide because of their superior clinical profiles, more predictable pharmacokinetics, and hence more convenient dosing relative to other anticoagulants. However, the optimal dosing of DOACs in extreme bodyweight  patients and patients with renal impairment is difficult to achieve using the conventional dosing approach. The standard dosing approach (fixed-dose) is based on limited data from clinical studies. The existing formulae (models) for determining the appropriate doses for these patient groups leads to suboptimal dosing. This problem of mis-dosing is worsened by the lack of standardized laboratory parameters for monitoring the exposure to DOACs in renal failure and extreme bodyweight patients. Model-informed precision dosing (MIPD) encompasses a range of techniques like machine learning and pharmacometrics modelling, which could uncover key variables and relationships as well as shed more light on the pharmacokinetics and pharmacodynamics of DOACs in patients with extreme bodyweight or renal impairment. Ultimately, this individualized approach—if implemented in clinical practice—could optimise dosing for the DOACs for better safety and efficacy.

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  1. Department of Pharmacy, School of Applied Sciences, University of Huddersfield, Queensgate, Huddersfield, HD1 3DH, West Yorkshire, UK

    Ezekwesiri Michael Nwanosike, Hamid A. Merchant, Barbara R. Conway & Syed Shahzad Hasan

  2. Calderdale and Huddersfield Anticoagulation Unit, Calderdale and Huddersfield NHS Foundation Trust Hospital, Lindley, Huddersfield, HD3 3EA, UK

    Wendy Sunter

  3. School of Computing and Engineering, University of Huddersfield, Queensgate, Huddersfield, HD1 3DH, UK

    Muhammad Ayub Ansari

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Ezekwesiri Michael Nwanosike, Wendy Sunter, Hamid A. Merchant, Barbara R. Conway, Muhammad Ayub Ansari, and Syed Shahzad Hasan declare that they have no potential conflicts.

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Nwanosike, E.M., Sunter, W., Merchant, H.A. et al. Challenges and Possible Solutions to Direct-Acting Oral Anticoagulants (DOACs) Dosing in Patients with Extreme Bodyweight and Renal Impairment. Am J Cardiovasc Drugs 23, 9–17 (2023). https://doi.org/10.1007/s40256-022-00560-7

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