Off-Label Dosing of Direct Oral Anticoagulants Among Inpatients with Atrial Fibrillation in the United States

Circulation: Cardiovascular Quality and Outcomes, Ahead of Print.
Background: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 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 were stratified according to receipt of under, over, or recommended dosing. Factors associated with off-label dosing (defined as under or overdosing) were identified using logistic regression. Median odds ratio and time-series analyses were used to assess hospital-level variation and temporal trends, respectively.Results:Of 22,470 patients (70.1 +/- 12.1 years, 48.1% female, 82.5% White) 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%). The overall rate of off-label dosing was 11.2%. Patient-related factors associated with off-label dose 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 dose 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. Over the study period, recommended dosing significantly increased over time (81.9% to 90.9%, p<0.0001 for trend) with a corresponding decline in under (14.4% to 6.6%, p<0.0001 for trend) and overdosing (3.8% to 2.5%, p=0.001 for trend).Conclusions:Over 1 in 10 patients hospitalized for AF is discharged on an off-label DOAC dose with significant variation across hospitals. While the proportion of patients receiving recommended dosing has significantly improved over time, opportunities to improve DOAC dosing persist.



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