Frailty as a Marker for the Plasma Concentrations of Direct Oral Anticoagulants in Older Patients: Results of an Exploratory Study.

Abstract

Frailty makes older adults vulnerable to adverse health outcomes and can modify pharmacokinetics and drug exposure. We aimed to explore the relationship between different frailty assessments and trough plasma concentrations of direct oral anticoagulants in older patients. The frailty status of adults aged ≥70 years receiving regular direct oral anticoagulant medication was assessed by four different instruments: Fried physical phenotype, Rockwood frailty index, Short Physical Performance Battery, and FRAIL scale. The two performance measures "slow gait speed" and "weak grip strength" were used to build a separate score depending on the number of positive criteria (none, one, two). For each participant, a single steady-state direct oral anticoagulant trough plasma concentration was collected, dose-normalized, and its relationship to the various frailty assessments analyzed. Forty-two participants completed the study, with most using apixaban (n = 22). Dose-normalized apixaban trough concentrations were 2.48-fold higher in frail participants (Fried phenotype) than in robust participants (p = 0.009) and correlated positively with Fried physical phenotype (rs = 0.535, p = 0.010) and negatively with Short Physical Performance Battery (rs = -0.434, p = 0.044). Compared with participants who met none of the criteria "slow gait speed" and "weak grip strength", apixaban trough concentrations were approximately 1.9-fold higher in participants who were positive for one (p = 0.018) or two (p = 0.013) of these measures. In this exploratory study, higher levels of frailty on performance-based frailty assessments were associated with higher apixaban exposure in older adults. German Clinical Trials Register DRKS00016741; registered 20 February, 2019.