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

Abstract

This article aims to highlight the dosing issues of direct oral anticoagulants (DOACs) in patients with renal insufficiency 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 weight patients and patients with renal impairment is difficult to achieve using 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 lead to suboptimal dosing. This problem of mis-dosing is worsened by the lack of standardised laboratory parameters for monitoring the exposure to DOACs in renal failure and extreme body weight 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 body weight or renal impairment. Ultimately, this individualised approach-if implemented in clinical practicecould optimise the DOACs dosing for better safety and efficacy.

A real-world study of different doses of rivaroxaban in patients with nonvalvular atrial fibrillation

“…However, due to the inter-individual variability of pharmacokinetics, insufficient anticoagulation or excessive anticoagulation may still occur, especially as the clinical application of rivaroxaban becomes more and more widespread, and the safety issue in emergencies or special circumstances has gradually attracted clinical attention. [4] Many physicians tend to use smaller doses to reduce the risk of bleeding, which in turn often results in insufficient anticoagulation, and these problems plague physicians and largely affect the rational use of the drug. Although both the European Society of Cardiology (ESC) guidelines [2] and the American College of Cardiology guidelines [5] recommend 20 mg/d as a stroke-prevention dose for nonvalvular NVAF, fewer patients were given the 20 mg dose due to physicians' concerns about bleeding, so the 15 mg/d and 10 mg/d doses have been commonly used in Asian patients with NVAF.…”