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The effect of non-recommended dosing of non-vitamin K antagonist oral anticoagulants (NOACs) on 1-year mortality in patients with newly diagnosed AF? Results from the GARFIELD-AF registry
Authors : A J Camm (London,GB), F Cools (Brasschaat,BE), S Virdone (London,GB), J-P Bassand (Besançon,FR), D A Fitzmaurice (Coventry,GB), KAA Fox (Edinburgh,GB), S Z Goldhaber (Boston,US), S Goto (Kanagawa,JP), S Haas (Munich,DE), L G Mantovani (Monza,IT), K Pieper (London,GB), A G G Turpie (Hamilton,CA), F W A Verheugt (Amsterdam,NL), A K Kakkar (London,GB)
A.J. Camm1
,
F. Cools2
,
S. Virdone3
,
J.-P. Bassand4
,
D.A. Fitzmaurice5
,
K.A.A. Fox6
,
S.Z. Goldhaber7
,
S. Goto8
,
S. Haas9
,
L.G. Mantovani10
,
K. Pieper11
,
A.G.G. Turpie12
,
F.W.A. Verheugt13
,
A.K. Kakkar14
,
1St. George's University of London and Imperial College - London - United Kingdom
,
2AZ KLINA Cardiology - Brasschaat - Belgium
,
3Thrombosis Research Institute - London - United Kingdom
,
4Thrombosis Research Institute, London, UK and University of Besançon - Besançon - France
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5University of Warwick Medical School - Coventry - United Kingdom
,
6University of Edinburgh - Edinburgh - United Kingdom
,
7Brigham and Women's Hospital and Harvard Medical School - Boston - United States of America
,
8Tokai University School of Medicine - Kanagawa - Japan
,
9Formerly Department of Medicine, Technical University of Munich - Munich - Germany
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10University of Milan Bicocca - Monza - Italy
,
11Duke Clinical Research Institute, Durham, NC, USA & Thrombosis Research Institute - London - United Kingdom
,
12McMaster University - Hamilton - Canada
,
13Onze Lieve Vrouwe Gasthuis (OLVG) - Amsterdam - Netherlands
,
14Thrombosis Research Institute and University College London - London - United Kingdom
,
Background: The recommended doses for a NOAC to prevent stroke and systemic embolism (SE) in patients with non-valvular atrial fibrillation (AF) are specified in the prescribing information. Prospective observational studies provide an opportunity to evaluate whether the actual dosing of these drugs in real-life conforms with the approved dosing.
Methods: This analysis assesses the impact of NOAC dosing (i.e., recommended vs. non-recommended) on all-cause mortality at 1 year in patients in newly diagnosed AF. Of patients enrolled consecutively into the Global Anticoagulant Registry in the FIELD-AF (GARFIELD-AF) between Apr-2013 and Sep-2015, 10,417 from 35 countries were eligible for this analysis: rivaroxaban (n=4490, 43.1%), apixaban (n=3283, 31.5%), dabigatran (n=2359, 22.6%) and edoxaban (n=285, 2.7%). Recommended dosing was determined according to differing country criteria, including: impaired kidney function and/or low body weight (≤60 kg) or age ≥80 yrs.
Results: Compared with patients who received the recommended dose, non-recommended dosing according to country-specific guidelines was associated with a higher all-cause mortality. The hazard ratios were: 1.51, 95% confidence interval 1.16 to 1.96 (for dosing below recommendations) and 1.57, 95% CI 0.97 to 2.56 (for dosing above recommendations) after adjusting for age, sex, ethnicity, smoking, alcohol consumption, diabetes, hypertension, history of bleeding, history of stroke/TIA, heart failure, vascular disease, and AF type. Prescribing patterns according to country-specific guidelines are reported in the figure. More than 70% of patients received the correct dose of rivaroxaban, apixaban or dabigatran. Treatment below the recommended doses with rivaroxaban or apixaban was more common in patients from Japan (38.0% [rivaroxaban], 39.4% [apixaban]) than other regions (17.8% [rivaroxaban], 24.0% [apixaban]). Patients on edoxaban were more likely to receive doses below the recommendations compared with the other NOACs; approximately two-thirds of these patients were from Japan. Few patients (3.6%, overall) were treated above the recommended doses. Of those who were treated over the recommended doses, 67.7% had moderate-to severe CKD. By comparison, 8.9% of patients on recommended doses and 7.1% on non-recommended low-doses had moderate-to severe CKD.
Conclusion: Since the introduction of NOACs, most patients receive the recommended NOAC doses according to country-specific guidelines. Treatment above the recommended doses is relatively rare compared with non-recommended low dosing. Prescription of non-recommended doses is associated with an increased the risk of death compared with patients on recommended doses, even after adjusting for baseline factors.
ESC Professional Members, Association Members (Ivory & above) benefit from year-round access to all the resources from their respective Association, and to all content from previous years. Fellows of the ESC (FESC), and professionals in training or under 40 years old, who subscribed to a Young Combined Membership package benefit from access to all ESC 365 content from all events, all editions, all year long. Find out more about ESC Memberships here.