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

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.

Publikationsverlauf

Eingereicht: 04. April 2024

Angenommen: 14. Juli 2024

Accepted Manuscript online:
15. Juli 2024

Artikel online veröffentlicht:
30. Juli 2024

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