Appropriateness of Direct Oral Anticoagulant Dosing and its Relation to Drug Levels in Atrial Fibrillation Patients

Bruria Hirsh Raccah, Department of Cardiology, Hadassah University Hospital & Division of Clinical Pharmacy, Institute for Drug Research, School of Pharmacy, Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel (bruria.hirsh@mail.huji.ac.il)
Amihai Rottenstreich, Department Of Cardiology, Hadassah University Hospital, Jerusalem, Israel
Netanel Zacks, Hematology Department, Hadassah-Hebrew University Medical Center, Jerusalem, Israel
Ilan Matok, Division of Clinical Pharmacy, Institute For Drug Research, School Of Pharmacy, Faculty Of Medicine, Hebrew University Of Jerusalem, Jerusalem, Israel
Haim D. Danenberg , Department of Cardiology, Hadassah University Hospital, Jerusalem, Israel
Arthur Pollak , Department of Cardiology, Hadassah University Hospital, Jerusalem, Israel
Yosef Kalish, Hematology Department, Hadassah-Hebrew University Medical Center, Jerusalem, Israel

Introduction: Inappropriate low dosing of direct oral anticoagulants (DOACs), to a level that does not meet dose reduction criteria, is very common.  This raises concern regarding the adequacy of anticoagulation achieved.

Aim: To evaluate the relationship between inappropriate dosing and DOAC levels.

Methods: 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. A multivariate analysis was performed to assess the correlation between the appropriateness of dosing and the study outcomes.

Results: 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% of patients treated with appropriate dosing compared to 21% and 41.5% of patients treated with inappropriately low dose. DOAC levels above the expected range and in the highest quartile were found in 23.8% and 32.5% of patients treated with the appropriate dose compared to 7.1% and 9.4% of patients 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), P=0.011) on the other hand, appropriate dose was shown to predict drug levels in the highest quartile (odds ratio [95% CI]: 3.77 (0.12, 0.76), P=0.011).

Conclusion: Treatment with inappropriate 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.

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Abstract Reference & Short Personal Biography of Presenting Author

Amihai Rottenstreich and Bruria Hirsh Raccah contributed equally to this work.