Model-informed remedial dosing strategies for delayed or missed direct oral anticoagulant doses reduced the deviation time outside the therapeutic range by up to 14.4 hours compared to EHRA guidelines.
Do individualized remedial dosing strategies reduce deviation time outside the therapeutic range compared to current guidelines for delayed or missed DOAC doses?
Model-informed individualized remedial dosing strategies for delayed or missed DOAC doses reduce the time spent outside the therapeutic range compared to current guideline recommendations.
ABSTRACT: Nonadherence to direct oral anticoagulant (DOAC) pharmacotherapy may increase the risk of thromboembolism or bleeding, and delayed or missed doses are the most common types of nonadherence. Current recommendations from regulatory agencies or guidelines regarding this issue lack evidence and fail to consider individual differences. This study aimed to develop individual remedial dosing strategies when the dose was delayed or missed for DOACs, including rivaroxaban, apixaban, edoxaban, and dabigatran etexilate. Remedial dosing regimens based on population pharmacokinetic (PK)-pharmacodynamic (PD) modeling and simulation strategies were developed to expeditiously restore drug concentration or PD biomarkers within the therapeutic range. Population PK-PD characteristics of DOACs were retrieved from previously published literature. The effects of factors that influence PK and PD parameters were assessed for their impact on remedial dosing regimens. A web-based dashboard was established with R-shiny to recommend remedial dosing regimens based on patient traits, dosing schedules, and delay duration. Addressing delayed or missed doses relies on the delay time and specific DOACs involved. Additionally, age, body weight, renal function, and polypharmacy may marginally affect remedial strategies. The proposed remedial dosing strategies surpass current recommendations, with less deviation time beyond the therapeutic range. The online dashboard offers quick and convenient solutions for addressing missed or delayed DOACs, enabling individualized remedial dosing strategies based on patient characteristics to mitigate the risks of bleeding and thrombosis.
Liu et al. (Wed,) conducted a other in Nonvalvular atrial fibrillation, deep vein thrombosis, pulmonary embolism (n=1,000). Model-informed remedial dosing strategies vs. EHRA guideline recommendations was evaluated on Deviation time outside the on-therapy range. Model-informed remedial dosing strategies for delayed or missed direct oral anticoagulant doses reduced the deviation time outside the therapeutic range by up to 14.4 hours compared to EHRA guidelines.