Journal of Thrombosis and Thrombolysis

, Volume 48, Issue 3, pp 500–505 | Cite as

Creatinine monitoring patterns in the setting of direct oral anticoagulant therapy for non-valvular atrial fibrillation

  • Martin M. GrucaEmail author
  • Yun Li
  • Xiaowen Kong
  • Deborah DeCamillo
  • Eva Kline-Rogers
  • Mona A. Ali
  • Scott Kaatz
  • Musa Dahu
  • James B. Froehlich
  • Geoffrey D. Barnes


Guidelines and experts note that patients with atrial fibrillation require regular renal function monitoring to ensure safe use of direct oral anticoagulants (DOACs). Insufficient monitoring could lead to inappropriate dosing and adverse events. Our objective was to describe the frequency of insufficient creatinine monitoring among patients on DOACs, and to describe clinical factors associated with insufficient monitoring. We hypothesized that renal impairment would be associated with insufficient monitoring. A retrospective cohort study was performed with data from the Michigan Anticoagulant Quality Improvement Initiative. Patients were included if they initiated DOAC therapy for stroke prevention related to atrial fibrillation, remained on therapy for ≥ 1 year, and had baseline creatinine and weight measurements. Creatinine clearance (CrCl) was calculated via Cockcroft-Gault equation. Our outcome was the presence of insufficient creatinine monitoring, defined as: < 1 creatinine level/year for patients with CrCl > 50, or < 2 creatinine levels/year for patients with CrCl ≤ 50. Multivariable analysis was done via logistic regression. Study population included 511 patients. In overall, 14.0% of patients received insufficient monitoring. Among patients with CrCl > 50, 11.5% had < 1 creatinine level/year. Among patients with CrCl ≤ 50, 27.1% received < 2 creatinine levels/year. Baseline renal dysfunction was associated with a higher likelihood of insufficient creatinine monitoring (adjusted odds ratio 3.64, 95% confidence interval 1.81–7.29). This shows a significant gap in the monitoring of patients on DOACs—patients with renal impairment are already at higher risk for adverse events. Future studies are needed to describe the barriers in monitoring these patients and to identify how to optimally address them.


Atrial fibrillation Creatinine Factor Xa inhibitors Kidney diseases Drug monitoring 


Author contributions

Concept and design: MMG, YL, EKR, MAA, SK, MD, JBF, GDB. Acquisition, analysis, or interpretation of data: YL, XK, DD. Drafting of the manuscript: MMG. Critical revision of the manuscript for important intellectual content: MMG, YL, XK, DD, EKR, MAA, SK, MD, JBF, GDB. Statistical analysis: YL, XK. Obtained funding: JBF, GDB Administrative, technical, or material support: MMG, YL, XK, DD, EKR, MAA, SK, MD, JBF, GDB. Supervision: GDB


This study was supported by Blue Cross Blue Shield of Michigan Foundation and National Institute of Health/National Heart, Lung, Blood Institute (K01HL135392 to Geoffrey D. Barnes). The funding sources had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Compliance with ethical standards

Conflict of interest

Dr. Barnes reports grants from Pfizer/Bristol-Myers-Squib, Blue Cross Blue Shield of Michigan, National Heart Lung and Blood Institute during the conduct of the study. Dr. Barnes reports consulting fees from Pfizer/Bristol-Myers-Squib, Janssen, and Portola outside of the submitted work. Dr. Froehlich reports grant support from Blue Cross/Blue Shield of Michigan and the Fibromuscular Disease Society of America. Dr. Froehlich reports consulting fees for Merck, Janssen, and Novartis outside of the submitted work. Dr. Froehlich serves on the Advisory Committee of Boehringer-Ingelheim and Pfizer. Dr. Kaatz reports grants from Blue Cross Blue Shield of Michigan and Janssen during the conduct of the study. Dr. Kaatz reports consulting fees from Pfizer, Bristol Myer Squibb, Daiichi Sankyo, Portola, Roche, and Boehringer Ingelheim outside of the submitted work. Ms. Kline-Rogers reports consulting fees from Anticoagulation Forum and Janssen Pharmaceuticals outside of the submitted work. All other authors have no disclosures.

Ethical 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.

Informed consent

Given the retrospective nature of this study and the minimal risk that it presented to subjects, this study was granted a waiver of informed consent from our respective Institutional Review Board.

Supplementary material

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Copyright information

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

Authors and Affiliations

  • Martin M. Gruca
    • 1
    • 2
    Email author
  • Yun Li
    • 3
  • Xiaowen Kong
    • 1
  • Deborah DeCamillo
    • 1
  • Eva Kline-Rogers
    • 1
  • Mona A. Ali
    • 4
  • Scott Kaatz
    • 5
  • Musa Dahu
    • 6
  • James B. Froehlich
    • 1
  • Geoffrey D. Barnes
    • 1
  1. 1.Department of Internal Medicine, Frankel Cardiovascular CenterUniversity of Michigan Medical CenterAnn ArborUSA
  2. 2.Department of Internal Medicine, McGaw Medical CenterNorthwestern UniversityChicagoUSA
  3. 3.Department of Biostatistics, School of Public HealthUniversity of MichiganAnn ArborUSA
  4. 4.Beaumont HospitalRoyal OakUSA
  5. 5.Division of Hospital MedicineHenry Ford HospitalDetroitUSA
  6. 6.Spectrum Health SystemGrand RapidsUSA

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