Serum Concentrations and Elimination Rates of Direct-Acting Oral Anticoagulants (DOACs) in Older Hip Fracture Patients Hospitalized for Surgery: A Pilot Study

Abstract

Background

Use of direct-acting oral anticoagulants (DOACs) is increasing, but knowledge about pharmacokinetics and safety in frail patients is lacking.

Objective

The aim was to determine serum concentrations and elimination rates of DOACs in older hip fracture patients hospitalized for surgery.

Methods

The study included patients ≥ 65 years of age hospitalized for acute hip fracture surgery over a period of 6 months. Use of antithrombotic drugs was registered and serum samples collected for analysis of DOACs (apixaban, dabigatran and rivaroxaban) at admission and surgery. Measured concentrations were assessed in relation to reference (therapeutic) ranges of the respective drugs and applied for half-life calculations. Furthermore, waiting time for surgery was compared between DOAC and warfarin users.

Results

Of 167 patients included (median age 84 years), 11 and 14 used DOACs and warfarin, respectively. Seven of the DOAC-treated patients had concentrations above the upper reference range (> 300 nM) at admission, and concentrations were still in the reference range for five of these at surgery. Elimination half-lives could be estimated in eight patients and ranged between 14.6 and 59.7 h (median 21.6). The observed waiting time for surgery was longer for patients using DOACs than warfarin (median 44 vs. 25 h).

Conclusion

This pilot study indicates that older patients prone to hip fracture are at risk of being exposed to therapeutic serum concentrations of DOACs during surgery due to reduced drug elimination rates. The observation that almost 50% of the patients had therapeutic concentrations at surgery should be investigated further regarding safety of DOAC use in this frail elderly population.

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Acknowledgements

The authors are thankful to physicians and nurses at the orthogeriatric unit who contributed to the patient inclusion, blood sampling and registration of clinical data. We are also grateful to Undis Ellevog at the therapeutic drug monitoring laboratory, for performing serum concentration analyses of DOACs.

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Correspondence to Espen Molden.

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No external funding was used in the preparation of this manuscript.

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Authors KKV, IL, AHR and EM declare that they have no conflicts of interest that might be relevant to the contents of this manuscript.

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Viktil, K.K., Lehre, I., Ranhoff, A.H. et al. Serum Concentrations and Elimination Rates of Direct-Acting Oral Anticoagulants (DOACs) in Older Hip Fracture Patients Hospitalized for Surgery: A Pilot Study. Drugs Aging 36, 65–71 (2019). https://doi.org/10.1007/s40266-018-0609-4

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