Real-world assessment of off-label direct oral anticoagulant dosing for venous thromboembolism
Preferred anticoagulation therapy for venous thromboembolism (VTE) has shifted from warfarin to direct oral anticoagulants (DOACs). Adherence to DOAC prescribing information is an important quality measure as off-label doses have been associated with increased risk of adverse events (AEs). To identify the prevalence, outcomes, and patient characteristics associated with off-label DOAC dosing during VTE treatment. Patients receiving DOAC for VTE treatment discharged from University of Utah Health (UUH) over a 90-day period were identified. Dosing was classified as “labeled” or “off-label” based on concordance with manufacturer prescribing information. AEs (thromboembolic events, bleeding, death) occurring within 90 days after discharge were identified. Out of 195 patients, 154 (79.0%) received labeled dosing, 31 (15.9%) received off-label dosing, and 10 (5.1%) were indeterminate. Two-thirds of off-label doses were higher than recommended and three-fourths occurred during extended treatment (more than 90 days post-VTE). Off-label dosing rates dropped to 5.6% when 6-month dose reductions were not required. Off-label dosing was associated with apixaban use and extended phase treatment (p < 0.001). No association was found between off-label dosing and age, renal function, prescriber rationale for dose selection, or Thrombosis Clinic referral. AEs were experienced by 18 (11.7%) and 3 (9.7%) patients in the labeled and off-label groups, respectively (p = 0.77). Bleeding events comprised 46.2% of AEs. The rate of off-label DOAC dosing for VTE at UUH was within rates reported in prior studies, occurred primarily with extended-duration apixaban, and did not result in a higher rate of AEs.
KeywordsDirect oral anticoagulant Venous thromboembolism Off-label Dosing
This study received no external funding.
Compliance with ethical standards
Conflict of interest
John A. Saunders declares that he has no conflict of interest. Whitney L. Gustafson declares that she has no conflict of interest. Sara R. Vazquez declares that she is an editorial consult for UpToDate® and a member of the Anticoagulation Forum Board of Directors. Aubrey E. Jones declares that she has no conflict of interest. Daniel M. Witt declares that he is a member of the Anticoagulation Forum Advisory Council and has received grant funding unrelated to this study from Roche Diagnostics Corporation (RD003737).
All procedures performed in studies involving human participants were in accordance with the ethical standards of the University of Utah Institutional Review Board and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
Due to the retrospective chart review design of the study, the University of Utah Institutional Review Board waived the requirement for informed consent.
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