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Direct-acting oral anticoagulant drug level monitoring in clinical patient management

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Abstract

The role of drug-level monitoring among patients using direct-acting oral anticoagulant (DOAC) is unclear. We aimed to investigate its ‘real-life’ utilization and effect on clinical management. A review of records of patients who underwent DOAC level testing during 2013–2017. Overall, 212 patients (median age 77 years) underwent 292 DOAC measurements [apixaban (n = 147), rivaroxaban (n = 102), dabigatran (n = 43)]. Monitoring volume increased by 460% during study period. DOAC level testing was performed during routine follow-up in 51 (17.5%) cases, whereas the remaining 241 (82.5%) measurements were performed due to selected clinical circumstances, most commonly: bleeding (n = 60), perioperative status (n = 45), breakthrough thrombosis (n = 37) and renal failure (n = 35). Drug levels were within the expected range in 210 (71.9%), above the expected range in 62 (21.2%) and lower than expected range in 20 (6.8%). In multivariate analysis, older age (P = 0.005), lower glomerular filtration rate (P = 0.001) and lower body mass index (P = 0.006) were associated with DOAC levels above the expected range. Clinical decisions were affected by DOAC monitoring following most (140/241, 58.1%) measurements for which we identified an indication for testing; yet only rarely when monitoring was performed during routine follow-up (7.8%, 4/51) (P < 0.0001). While no benefit of routine DOAC monitoring was observed, drug level measurement has an important role in the management of patients in selected circumstances. Age, body weight and creatinine clearance were found to be significant predictors of drug levels. Future studies are warranted to establish associations between drug levels and outcomes, and better delineate the role of DOAC monitoring.

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Abbreviations

BMI:

Body mass index

DOAC:

Direct acting oral anticoagulant

eGFR:

Estimated glomerular filtration rate

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Acknowledgements

Netanel Zacks’s participation in this study was performed in fulfillment of research requirements toward the MD degree. We thank Ms. Cindy Cohen for her editorial assistance.

Funding

No external funding was used in this conduct of this study.

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Authors and Affiliations

Authors

Contributions

All authors-study concept, design, review and approval of the final manuscript. AR, NZ, BHR, GK, BR and YK reviewed the literature and wrote the paper. Authors AR, YK, ND and NZ collected the data.

Corresponding author

Correspondence to Yosef Kalish.

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Conflict of interest

The authors declare that they have no conflicts of interest.

Ehical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. This study was approved by the local institutional review board of Hadassah Medical Center Helsinki Committee (IRB approval number No. HMO 0126-17).

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Informed consent was obtained from all individual participants included in the study.

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Rottenstreich, A., Zacks, N., Kleinstern, G. et al. Direct-acting oral anticoagulant drug level monitoring in clinical patient management. J Thromb Thrombolysis 45, 543–549 (2018). https://doi.org/10.1007/s11239-018-1643-0

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