Dilemmas Related to Direct-Acting Oral Anticoagulant Administration in Patients With Extreme Obesity

Objective: The objective of the study was to discuss the controversies surrounding the use and dosing of direct-acting oral anticoagulants (DOACs) in obese patients recognizing the limitations of the existing evidence base that preclude strong recommendations. Data Sources: A literature search of MEDLINE was performed (2020 to end August 2022) subsequent to recent guidelines using the following search terms: direct acting anticoagulants, obesity, rivaroxaban, apixaban, edoxaban, dabigatran, dabigatran etexilate, and clinical practice guidelines. Study Selection and Data Abstraction: English-language studies and those conducted in adults were selected. Data Synthesis: The available randomized studies evaluating DOACs had relatively small numbers of patients with more extreme forms of obesity (body mass index [BMI] > 40 kg/m²) and none of the larger studies had a specific focus on dosing DOACs in obese patients. Recent guidelines by the International Society on Thrombosis and Haemostasis (ISTH) have specific recommendations for dosing DOACs in obesity. There are pharmacokinetic/pharmacodynamic and observational studies published before and after the ISTH guidelines with a focus on DOAC dosing in obese patients that generally support the recommendations in the guidelines, but most involved small numbers of patients usually with BMIs <45 kg/m². Relevance to Patient Care and Clinical Practice: This review discusses DOAC dosing in obesity with important considerations for clinicians related to DOAC choice and dosing. Conclusions: Dosing alterations of DOACs do not appear to be necessary when used for either prophylaxis or treatment in patients with BMIs up to approximately 45 to 50 kg/m², but research is needed for BMIs >50 kg/m².