How to handle the delayed or the missed dose of edoxaban in patients
with non-valvular atrial fibrillation: model-informed remedial strategy
Aim: Edoxaban is a non-vitamin K antagonist oral anticoagulant (NOAC)
widely used for long-term stroke prevention in patients with
non-valvular atrial fibrillation (NVAF). Adherence to NOACs is
unsatisfactory and decreases over time. The aim of this study was to
explore appropriated remedial dosing regimens for non-adherent
edoxaban-treated NVAF patients through the Monte Carlo simulation.
Methods: Six proposed regimens were compared with the recommendations in
the European Heart Rhythm Association (EHRA) guide regarding the trough
total deviation time considering both edoxaban plasma concentration and
inactive factor Xa activity. Monte Carlo simulations were performed
using RxODE based on the published population
pharmacokinetics/pharmacodynamics model. Results: The proposed remedial
strategies were different from EHRA recommendations and were related to
delay duration. The missed dose can be taken immediately if the delay
time is within 11 h. When the delay period is between 12 and 19 h, a
half dose followed by a regular dosing schedule is recommended. When the
delay time exceeds 19 h, a full dose followed by a half dose is
preferred compared to that recommended in the EHRA guide. Our proposed
strategies resulted in a shorter total deviation time than EHRA guide.
Conclusion: PK/PD modelling and simulation are effective in developing
and evaluating the remedial strategies of edoxaban, which could help
maximize its therapeutic effect.