Pharmacokinetics and Dosing Regimens of Direct Oral Anticoagulants in Morbidly Obese Patients: An Updated Literature Review

Abstract

Data on the impact of morbid obesity (body mass index [BMI] ≥ 40 kg/m²) on the pharmacokinetics (PK), pharmacodynamics (PD) of direct oral anticoagulants (DOACs) are relatively limited, making it difficult to design optimal dosing regimens in morbidly obese patients.To review literature on PK/PD profile, efficacy, and safety of DOACs in venous thromboembolism (VTE) and nonvalvular atrial fibrillation (AF) patients with morbid obesity and make recommendations regarding optimal dosing regimens in these patient populations.A detailed literature search was conducted (from inception to June 22, 2022) for relevant articles involving PK/PD and clinical data on DOACs use in morbidly obese patients with VTE or AF, or healthy volunteers.A total of 28 studies were identified. DOAC-specific PK variations and clinical outcomes have been observed. Obesity may have a modest effect on PK/PD of dabigatran, apixaban, or rivaroxaban. Dabigatran was effective in AF patients with morbid obesity but might increase the risk of gastrointestinal bleeding. Standard dosing of apixaban or rivaroxaban is effective and safe for VTE and AF patients with morbid obesity. Trough edoxaban concentration and anti-Xa activity were similar in different BMI groups (18.5 to >40 kg/m²), and standard dosing of edoxaban may be effective and safe for AF patients.Current evidence suggests dabigatran should be used with caution in patients with AF as it might increase the risk of gastrointestinal bleeding; Standard dosing of apixaban or rivaroxaban can be used in VTE or AF patients; Standard dosing of edoxaban may be considered in AF patients.

Keywords: direct oral anticoagulants; drug dosing; morbid obesity; pharmacodynamics; pharmacokinetics.