Insights into the Pharmacokinetics and Pharmacodynamics of Direct Oral Anticoagulants in Older Adults with Atrial Fibrillation: A Structured Narrative Review

Older adults, the fastest growing population, represent almost 50% of all users of direct oral anticoagulants (DOACs). Unfortunately, we have very little relevant pharmacological and clinical data on DOACs, especially in older adults with geriatric profiles. This is highly relevant as pharmacokinetics and pharmacodynamics (PK/PD) often differ substantially in this population. Hence, we need to obtain a better understanding of the PK/PD of DOACs in older adults, to ensure appropriate treatment. This review summarises the current insights into PK/PD of DOACs in older adults. A search was undertaken up to October 2022 to identify PK/PD studies of apixaban, dabigatran, edoxaban, and rivaroxaban, that included older adults aged ≥ 75 years. This review identified 44 articles. Older age alone did not influence exposure of edoxaban, rivaroxaban and dabigatran, while apixaban peak concentrations were 40% higher in older adults than in young volunteers. Nevertheless, high interindividual variability in DOAC exposure in older adults was noted, which can be explained by distinctive older patient characteristics, such as kidney function, changes in body composition (especially reduced muscle mass), and co-medication with P-gp inhibitors, which is in line with the current dosing reduction criteria of apixaban, edoxaban, and rivaroxaban. Dabigatran had the largest interindividual variability among all DOACs since its dose adjustment criterion is only age, and thus it is not a preferable option. Additionally, DOAC exposure, which fell outside of on-therapy ranges, was significantly related to stroke and bleeding events. No definite thresholds linked to these outcomes in older adults have been established.