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Published on: February 26, 2013
Off-Label Dosing of Direct Oral Anticoagulants Among Inpatients With Atrial Fibrillation in the United States
Amneet Sandhu1,2, Lisa A Kaltenbach3, Karen Chiswell3
1Section of Cardiology, Denver VA Medical Center, Aurora, CO (A.S., P.M.H., P.D.V., P.L.H.).
Insights
Over 10% of atrial fibrillation patients receive incorrect direct oral anticoagulant (DOAC) doses post-hospitalization. While dosing accuracy improved over time, significant hospital variations and opportunities for optimization remain.
Area of Science:
- Cardiology
- Pharmacology
- Health Services Research
Background:
- Direct oral anticoagulants (DOACs) are crucial for preventing stroke in atrial fibrillation (AF) patients.
- Optimal DOAC dosing is essential but challenging, especially post-hospitalization.
- Current data on off-label DOAC dosing patterns in hospitalized AF patients is limited.
Purpose of the Study:
- To determine the frequency of off-label DOAC dosing (underdosing and overdosing) in hospitalized AF patients.
- To identify patient- and hospital-level factors associated with off-label DOAC dosing.
- To analyze temporal trends and hospital variation in DOAC dosing practices.
Main Methods:
- Analysis of the Get With The Guidelines-Atrial Fibrillation registry (January 2014–March 2020).
- Stratification of 22,470 patients discharged on DOACs into underdosing, overdosing, or recommended dosing groups.
- Logistic regression and time-series analyses to identify associated factors, hospital variation, and trends.
Main Results:
- 11.2% of AF patients received off-label DOAC doses (8.9% underdosed, 2.3% overdosed).
- Patient factors like age, dialysis dependence, sex, and weight were associated with off-label dosing.
- Significant hospital-level variation in off-label dosing was observed (median OR 1.45).
Conclusions:
- Off-label DOAC dosing is prevalent in hospitalized AF patients, with notable hospital variation.
- Recommended dosing increased significantly over the study period, while off-label use decreased.
- Despite improvements, optimizing DOAC dosing in AF patients remains an ongoing clinical challenge.
Background:
Among patients hospitalized for atrial fibrillation, 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 registry, patients admitted from January 1, 2014, to March 31, 2020, and discharged on DOACs were stratified according to receipt of underdosing, overdosing, or recommended dosing. Factors associated with off-label dosing (defined as underdosing or overdosing) were identified using logistic regression. Median odds ratio (OR) 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 atrial fibrillation (66% apixaban, 29% rivaroxaban, and 5% dabigatran), underdosing occurred among 2006 (8.9%), overdosing among 511 (2.3%), and recommended dosing among 19 953 (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]; overdosing: OR, 1.07 per 1-year increase [95% CI, 1.06-1.09]), dialysis dependence (underdosing: OR, 5.50 [95% CI, 3.76-8.05]; overdosing: OR, 5.47 [95% CI, 2.74-10.88]), female sex (overdosing: OR, 0.79 [95% CI, 0.63-0.99]), and weight (overdosing: OR, 0.96 per 1-kg increase [95% CI, 0.95-1.00]). Across hospitals, the adjusted median OR for off-label DOAC dose was 1.45 (95% CI, 1.34-1.65; underdosing: OR, 1.52 [95% CI, 1.39-1.76]; overdosing: OR, 1.32 [95% CI, 1.20-1.84]), indicating significant hospital-level variation. Over the study period, recommended dosing significantly increased over time (81.9%-90.9%; P<0.0001 for trend) with a corresponding decline in underdosing (14.4%-6.6%; P<0.0001 for trend) and overdosing (3.8%-2.5%; P=0.001 for trend).
Conclusions:
Over 1 in 10 patients hospitalized for atrial fibrillation are 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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