Frequency and Outcomes of Reduced Dose Non-Vitamin K Antagonist Anticoagulants: Results From ORBIT-AF II (The Outcomes Registry for Better Informed Treatment of Atrial Fibrillation II)

Benjamin A Steinberg, Peter Shrader, Karen Pieper, Laine Thomas, Larry A Allen, Jack Ansell, Paul S Chan, Michael D Ezekowitz, Gregg C Fonarow, James V Freeman, Bernard J Gersh, Peter R Kowey, Kenneth W Mahaffey, Gerald V Naccarelli, James A Reiffel, Daniel E Singer, Eric D Peterson, Jonathan P Piccini, Outcomes Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT‐AF) II Investigators, Benjamin A Steinberg, Peter Shrader, Karen Pieper, Laine Thomas, Larry A Allen, Jack Ansell, Paul S Chan, Michael D Ezekowitz, Gregg C Fonarow, James V Freeman, Bernard J Gersh, Peter R Kowey, Kenneth W Mahaffey, Gerald V Naccarelli, James A Reiffel, Daniel E Singer, Eric D Peterson, Jonathan P Piccini, Outcomes Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT‐AF) II Investigators

Abstract

Background: Non-vitamin K antagonist oral anticoagulants (NOACs) are indicated for stroke prevention in atrial fibrillation (AF) but require lower doses in certain patients. We sought to describe the frequency, appropriateness (according to Food and Drug Administration labeling), and outcomes of patients prescribed reduced doses of NOACs in community practice.

Methods and results: We analyzed data from the ORBIT-AF II (The Outcomes Registry for Better Informed Treatment of Atrial Fibrillation II) registry, a prospective, national, observational registry of AF patients. Among 7925 AF patients receiving NOACs, we assessed patterns of use of reduced NOAC doses and associated cardiovascular and bleeding outcomes at median follow-up of 1 year. Overall, 6636 patients (84%) received a NOAC at standard dose, which was consistent with US Food and Drug Administration labeling in 6376 (96%). Reduced NOAC dose was prescribed to 1289 (16% overall), which was consistent with Food and Drug Administration labeling in only 555 patients (43%). Compared with those whose NOAC dose was appropriately reduced, patients receiving inappropriate dose reductions were younger (median age 79 versus 84, P<0.0001) and had lower ORBIT bleeding risk scores (26% ≥4 versus 45%, P<0.0001). Compared with those appropriately receiving standard dosing, patients receiving inappropriately reduced-dose NOACs had higher unadjusted rates of thromboembolic events (2.11 versus 1.35 events per 100 patient years, hazard ratio 1.56, 95% confidence interval 0.92-2.67) and death (6.77 versus 2.60, hazard ratio 2.61, 95% confidence interval 1.86-3.67). After adjustment, outcomes were not significantly different but tended to favor patients dosed appropriately.

Conclusions: The majority of dose reductions of NOACs in AF are inconsistent with US Food and Drug Administration recommendations. There appear to be opportunities to improve current NOAC dosing in community practice.

Clinical trial registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01701817.

Keywords: atrial fibrillation; dosing; non–vitamin K antagonist oral anticoagulant; outcome.

© 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Figures

Figure 1
Figure 1
Dosing of NOACs according the US package labeling (“Appropriate” vs “Inappropriate”) for patients receiving standard and reduced dosing. NOAC indicates non–vitamin K antagonist oral anticoagulant.
Figure 2
Figure 2
Dosing of NOACs according the US package labeling (“Appropriate” vs “Inappropriate”) for patients receiving standard and reduced dosing, across ORBIT (The Outcomes Registry for Better Informed Treatment) bleeding score levels (in the 7577 patients with bleeding score available). NOAC indicates non–vitamin K antagonist oral anticoagulant.

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