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Open Access 13-01-2023 | Direct Oral Anticoagulant | Original Research Article

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

Authors: Annette Eidam, Julian Marji, Petra Benzinger, Kathrin I. Foerster, Jürgen Burhenne, David Czock, Felicitas Stoll, Antje Blank, Gerd Mikus, Walter E. Haefeli, Jürgen M. Bauer

Published in: Drugs & Aging | Issue 2/2023

Abstract

Background

Frailty makes older adults vulnerable to adverse health outcomes and can modify pharmacokinetics and drug exposure.

Objective

We aimed to explore the relationship between different frailty assessments and trough plasma concentrations of direct oral anticoagulants in older patients.

Methods

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.

Results

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 (r_s = 0.535, p = 0.010) and negatively with Short Physical Performance Battery (r_s = − 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.

Conclusions

In this exploratory study, higher levels of frailty on performance-based frailty assessments were associated with higher apixaban exposure in older adults.

Clinical Trial Registration

German Clinical Trials Register DRKS00016741; registered 20 February, 2019.

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Title: Frailty as a Marker for the Plasma Concentrations of Direct Oral Anticoagulants in Older Patients: Results of an Exploratory Study
Authors: Annette Eidam
Julian Marji
Petra Benzinger
Kathrin I. Foerster
Jürgen Burhenne
David Czock
Felicitas Stoll
Antje Blank
Gerd Mikus
Walter E. Haefeli
Jürgen M. Bauer
Publication date: 13-01-2023
Publisher: Springer International Publishing
Keywords: Direct Oral Anticoagulant
Apixaban
Direct Oral Anticoagulant
Published in: Drugs & Aging / Issue 2/2023
Print ISSN: 1170-229X
Electronic ISSN: 1179-1969
DOI: https://doi.org/10.1007/s40266-022-00999-y

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