Appropriateness of direct oral anticoagulant dosing and its relation to drug levels in atrial fibrillation patients

  • Bruria Hirsh Raccah
  • Amihai Rottenstreich
  • Netanel Zacks
  • Ilan Matok
  • Haim D. Danenberg
  • Arthur Pollak
  • Yosef KalishEmail author


Direct oral anticoagulants (DOACs) are commonly administered at a level that is lower than that recommended by dose reduction criteria. This raises concern regarding the adequacy of anticoagulation achieved. To evaluate the relationship between inappropriate dosing and DOAC levels. Medical records of atrial fibrillation patients who underwent DOAC level testing during 2013–2017 were reviewed. The primary outcomes were drug levels under and above the expected steady-state range, and in the lowest and highest quartiles. Of 143 patients who underwent DOAC measurements, only 87 (60.8%) received the appropriate dose. Levels under the expected range and in the lowest quartile were found in 11.9% and 15.0% of patients treated with appropriate dosing compared to 21% and 41.5% of patients treated with inappropriately low dose. DOAC levels were above the expected range and in the highest quartile in 23.8% and 32.5% of patients treated with the appropriate dose compared to 7.1% and 9.4% treated with inappropriately low dose. In multivariate analysis, the administration of an appropriate DOAC dose was associated with a lower rate of DOAC in the lowest level (adjusted odds ratio [95% CI] 0.30 (0.12, 0.76), P = 0.011). On the other hand, appropriate dose was associated with drug levels in the highest quartile (odds ratio [95% CI] 3.77 (0.12, 0.76), P = 0.011). Treatment with inappropriately low DOAC dosing compared to appropriate dose is associated with lower DOAC levels. However, among those treated with appropriate dosing, a higher proportion had high DOAC levels above the expected range.


Monitoring Direct-acting oral anticoagulants Drug levels Real life Dose reduction 



We thank Ms. Cindy Cohen for her editorial assistance.

Author contributions

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


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

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflicts of interest.

Informed consent

IRB approval waiving informed consent was obtained for this retrospective study.

Statement of human and animal rights

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).

Supplementary material

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Supplementary material 1 (DOCX 22 KB)


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of CardiologyHadassah University HospitalJerusalemIsrael
  2. 2.Division of Clinical Pharmacy, Institute for Drug Research, School of Pharmacy, Faculty of MedicineHebrew University of JerusalemJerusalemIsrael
  3. 3.Hematology DepartmentHadassah-Hebrew University Medical CenterJerusalemIsrael

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