Off-Label Dosing of Direct Oral Anticoagulants Among Inpatients with Atrial Fibrillation


Introduction: Among patients hospitalized for atrial fibrillation (AF), the frequency of off-label direct oral anticoagulant (DOAC) dosing, associated factors, hospital-level variation, and temporal trends in contemporary clinical practice are unknown. Methods: Using the Get With The Guidelines ® Atrial Fibrillation (GWTG-AF) registry, patients admitted from January 1st, 2014 to March 31st, 2020, and discharged on DOAC therapy were stratified according to receipt of underdosing, overdosing, or recommended dosing. Factors associated with off-label dosing were identified using logistic regression. Hospital-level variation and temporal trends were assessed. Results: Of 22,470 patients prescribed a DOAC at discharge from hospitalization for AF (66% apixaban, 29% rivaroxaban, 5% dabigatran), underdosing occurred among 2006 (8.9%), overdosing among 511 (2.3%), and recommended dosing among 19953 (88.8%). Patient-related factors associated with off-label DOAC use included age (underdosing: OR 1.06 per 1-year increase [95% CI 1.06-1.07] and overdosing: OR 1.07 per 1-year increase [1.06-1.09]), dialysis dependence (underdosing: OR 5.50 [3.76-8.05] and overdosing: OR 5.47 [2.74-10.88]), female sex (overdosing: OR 0.79 [0.63-0.99]) and weight (overdosing: OR 0.96 per 1-Kg increase [0.95-1.00]). Across hospitals, the adjusted median odds ratio for off-label DOAC use was 1.45 [95% CI 1.34-1.65] (underdosing: 1.52 [1.39-1.76] and overdosing: 1.32 [1.20-1.84]), indicating significant hospital-level variation. Hospital characteristics associated with underdosing included West vs. Northeast location (OR: 1.55 [1.04-2.31]), rural vs. urban setting (OR: 0.48 [0.28-0.83]), and number of beds (<200 vs. 500+, OR: 1.95 [1.29-2.95]). Recommended dosing significantly increased over time (81.9% in 2014 to 90.9% in 2020, p<0.0001 for trend) with a corresponding decline in underdosing (14.4% in 2014 to 6.6% in 2020, p<0.0001 for trend) and overdosing (3.8% in 2014 to 2.5% in 2020, p=0.001 for trend). Conclusion: One of 10 patients hospitalized for atrial fibrillation is discharged on off-label dosing of DOAC with significant variation across hospitals. While the proportion of patients receiving recommended dosing has significantly improved over time, opportunities to improve DOAC dosing persist.

Competing Interest Statement

The authors have declared no competing interest.

Funding Statement

The Get With The Guidelines®-AFIB (GWTG-AFIB) program is provided by the American Heart Association. GWTG-AFIB is sponsored, in part, by BMS Pfizer, Tylenol and Philips Image Guided Therapy.

Author Declarations

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

Not Applicable

The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

Each participating hospital received either human research approval to enroll cases without individual patient consent under the common rule, or a waiver of authorization and exemption from subsequent review by their institutional review board. The Duke Clinical Research Institute (Durham, NC) serves as the data analysis center and has an agreement to analyze the aggregate deidentified data for research purposes. The Institutional Review Board at Duke University Health approved this study. Participating sites were required to adhere to local regulatory and privacy procedures and obtain Institutional Review Board approval if needed. Institutional review board approval was granted to analyze limited data for research purposes.

I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.

Not Applicable

I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).

Not Applicable

I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.

Not Applicable

Data Availability

De-identified data will be made available upon request from the corresponding author, pending permission from the AHA-GWTG program.

Comments (0)

No login