Off-label DOAC Dosing Common in Hospitalized AF Patients, Too

Among patients hospitalized for atrial fibrillation (AF) or flutter, prescription of an off-label dose of a direct oral anticoagulant (DOAC) at discharge remains relatively common, according to data from a US quality-improvement registry.

A dose higher or lower than what is recommended on drug labeling was used in 11.2% of cases, although there was substantial variation across hospitals, researchers led by Amneet Sandhu, MD (University of Colorado Hospital, Aurora), report. That rate fell from 18.1% at the beginning of the roughly 6-year study period to 9.1% at the end.

“There’s a substantial amount of off-label dosing that we see for those that are hospitalized,” Sandhu told TCTMD, and these patients “may not be receiving the optimal balance between bleeding risk and stroke prevention that’s associated with DOAC use.”

Even though there were increases over time in use of recommended dosing, “there’s still room for improvement, and that room for improvement is likely in the understanding of who’s at risk and a systems-based approach and how to fix it,” Sandhu said.

The results were published online Monday in Circulation: Cardiovascular Quality and Outcomes ahead of the upcoming American Heart Association (AHA) 2023 Scientific Sessions in Philadelphia, PA, where Sandhu will present the study as a poster.

Get With The Guidelines – AFIB

Prior studies exploring the use of off-label DOAC doses have mostly involved outpatients, demonstrating frequent use of doses higher than what’s recommended on the drugs’ labeling (increasing bleeding risks) and lower-than-recommended doses (leading to suboptimal stroke protection). Such off-label prescribing of DOACs has been associated with greater risks of CV hospitalization and all-cause mortality.

Sandhu and his colleagues set out to explore whether these findings would translate to patients hospitalized for AF by using the AHA’s Get With The Guidelines–AFIB registry. The analysis included 22,470 patients (mean age 70.1 years; 48.1% women) who were admitted for atrial fibrillation or flutter between January 2014 and March 2020 and were discharged on a DOAC. Most (66%) received apixaban (Eliquis; Bristol Myers Squibb), 29% rivaroxaban (Xarelto; Bayer/Janssen), and 5% dabigatran (Pradaxa; Boehringer Ingelheim).

Overall, use of a lower-than-recommended dose was more common than overdosing (8.9% vs 2.3%). Older age and dialysis dependence were significantly associated with both underdosing and overdosing, whereas female sex and greater body weight correlated with a lower likelihood of receiving a dose higher than recommended.

Hospital-level factors also influenced the likelihood of underdosing, with centers located in the West or urban areas, and those with relatively few beds, being more likely to provide patients with DOAC doses lower than what’s recommended.

There was substantial variability in use of recommended DOAC dosing across hospitals, but overall, there was improvement over time. Declines from the beginning to the end of the study period were seen in rates of both underdosing (14.4% to 6.6%; P < 0.0001 for trend) and overdosing (3.8% to 2.5%; P = 0.001 for trend).

What Needs to Be Done

In order to increase recommended dosing of DOACs even further, Sandhu said the types of patients identified as being more at risk for receiving higher- or lower-than-recommended doses “should be carefully looked at when they’re discharged, perhaps with an early outpatient appointment focusing on DOAC dose.”

In addition, he said, “there’s some systems-level things that we can think about, like a multidisciplinary approach where pharmacy and pharmaceutical teams, hospital teams, and cardiology teams are working together, focusing on [at-risk patients], and thinking about what DOAC dose they should receive, perhaps in the inpatient ward.”

Key aspects of this type of team-based approach “may include the establishment of predischarge medication review processes, enhanced clinical decision support with automated dosing checks accounting for key comorbidities, medications, and up-to-date laboratory values embedded in the electronic medical record, and close outpatient follow-up attentive to the importance of appropriate DOAC dosing,” the investigators write.

Aside from quality-improvement programs, additional steps that can be taken at the level of the health system to address the use of nonrecommended DOAC dosing may include both benchmarking and implementation of performance goals, they say.

“Benchmarking such as that provided by quality-improvement registries like Get With The Guidelines–AFIB is likely an effective feedback mechanism to stimulate improvement,” they write. “In addition, establishment of provider- and facility-level AF performance measures related to appropriate AF dosing may also prove to be an effective feedback mechanism and policy incentive for continued quality improvement.”