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Thromb Haemost
DOI: 10.1055/a-2365-8681
Stroke, Systemic or Venous Thromboembolism

Timing of Off-Label Dosing of Direct Oral Anticoagulants in Three Large Health Systems

Grace C. Herron
1   Division of Cardiovascular Medicine, Department of Internal Medicine, Frankel Cardiovascular Center, University of Michigan, Ann Arbor, Michigan, United States
,
Deborah DeCamillo
1   Division of Cardiovascular Medicine, Department of Internal Medicine, Frankel Cardiovascular Center, University of Michigan, Ann Arbor, Michigan, United States
,
Xiaowen Kong
1   Division of Cardiovascular Medicine, Department of Internal Medicine, Frankel Cardiovascular Center, University of Michigan, Ann Arbor, Michigan, United States
,
Brian Haymart
1   Division of Cardiovascular Medicine, Department of Internal Medicine, Frankel Cardiovascular Center, University of Michigan, Ann Arbor, Michigan, United States
,
Scott Kaatz
2   Division of Hospital Medicine, Department of Medicine, Henry Ford Health, Detroit, Michigan, United States
,
Stacy Ellsworth
3   Department of Internal Medicine, Henry Ford Health, Detroit, Michigan, United States
,
Mona A. Ali
4   Department of Heart and Vascular Services, Corewell Health William Beaumont University Hospital, Royal Oak, Michigan, United States
,
Christopher Giuliano
5   Department of Pharmacy Practice, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, Detroit, Michigan, United States
6   Ascension St. John Hospital, Detroit, Michigan, United States
,
James B. Froehlich
1   Division of Cardiovascular Medicine, Department of Internal Medicine, Frankel Cardiovascular Center, University of Michigan, Ann Arbor, Michigan, United States
,
Geoffrey D. Barnes 
1   Division of Cardiovascular Medicine, Department of Internal Medicine, Frankel Cardiovascular Center, University of Michigan, Ann Arbor, Michigan, United States
› Author Affiliations Funding Funding for this study was provided by the Agency for Healthcare Research and Quality (R18HS026874). Blue Cross Blue Shield of Michigan and Blue Care Network provided funding for data abstraction and statistical analysis as part of the BCBSM Value Partnership program.
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Abstract

Background While direct oral anticoagulants (DOACs) may be viewed as simpler to manage then warfarin, they present their own unique management challenges resulting in frequent off-label dosing. It is unknown to what extent off-label dosing occurs when a patient is started on a DOAC versus later in their treatment.

Objectives We aimed to better characterize when off-label DOAC dosing is occurring and to evaluate the effectiveness of prescribing oversight using a registry-based intervention.

Methods We evaluated data from the Michigan Anticoagulation Quality Improvement Initiative (MAQI2) registry, a retrospective quality-improvement process using data abstractors, from 2018 to 2022 on the number of “alerts” that are generated in response to dosing deviating from the U.S. Food and Drug Administration instructions for atrial fibrillation (AF) and venous thromboembolism (VTE).

Results Among a sample of 789 to 1,022 annual AF patients and 381 to 484 annual VTE patients prescribed a DOAC in the MAQI2 registry, off-label dosing was relatively common. Over the 5-year period (2018–2022), there were 569 alerts for AF patients and 162 alerts for VTE patients. Alerts occurred more frequently during follow-up than at the time of initial prescribing in AF patients (78.2 vs. 21.8%), but more commonly at initial prescribing in VTE patients (59.9 vs. 40.1%). After initial review by quality-improvement abstractors, 19.3% of AF alerts and 14.8% of VTE alerts resulted in contact to the prescriber. When the prescriber was contacted, it led to an intervention about 75% of the time for both populations. The most common intervention was a change in DOAC dosing.

Conclusion This study demonstrates the benefit of DOAC prescribing oversight using a registry-based intervention to monitor for off-label dosing for the entirety of the time period a patient is prescribed DOAC, particularly for patients with AF, as off-label prescribing occurs frequently during the follow-up period.

Keywords

DOACs - off-label - registry

Note

Although Blue Cross Blue Shield of Michigan (BCBSM) and the Michigan Anticoagulation Quality Improvement Initiative work collaboratively, the opinions, beliefs, and viewpoints expressed by the authors do not necessarily reflect the opinions, beliefs, and viewpoints of BCBSM or any of its employees.


Authors' Contribution

G.C.H. and G.D.B. developed the research question. X.K. performed statistical analysis. G.C.H. drafted the initial manuscript. D.D., X.K., B.H., S.K., S.E., M.A.A., C.G., J.B.F., and G.D.B. reviewed the manuscript, made significant revisions, and approved the final version.


Ethical Approval Statement

Institutional review board approval was obtained at each participating site with a waiver of informed consent.


Supplementary Material



Publication History

Received: 04 April 2024

Accepted: 14 July 2024

Accepted Manuscript online:
15 July 2024

Article published online:
30 July 2024

© 2024. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

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