TY - JOUR
T1 - Frequency and outcomes of reduced dose Non-Vitamin K antagonist anticoagulants
T2 - Results from ORBIT-AF II (The outcomes registry for better informed treatment of atrial fibrillation II)
AU - on behalf of The Outcomes Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT-AF) II Investigators
AU - Steinberg, Benjamin A.
AU - Shrader, Peter
AU - Pieper, Karen
AU - Thomas, Laine
AU - Allen, Larry A.
AU - Ansell, Jack
AU - Chan, Paul S.
AU - Ezekowitz, Michael D.
AU - Fonarow, Gregg C.
AU - Freeman, James V.
AU - Gersh, Bernard J.
AU - Kowey, Peter R.
AU - Mahaffey, Kenneth W.
AU - Naccarelli, Gerald V.
AU - Reiffel, James A.
AU - Singer, Daniel E.
AU - Peterson, Eric D.
AU - Piccini, Jonathan P.
AU - Sobti, Sanjiv
AU - Alfieri, Anthony
AU - Bacon, James
AU - Bedwell, Noel
AU - Berry, John
AU - Bhagwat, Ravi
AU - Bloom, Stephen
AU - Boccalandro, Fernando
AU - Parilak, Leonard
AU - Capo, James
AU - Kapadia, Shaival
AU - Edwin Morriss, J.
AU - Muneer, Basharat
AU - Gogia, Harinder
AU - Herzog, William
AU - Hotchkiss, David
AU - Ip, John
AU - Jaffrani, Naseem
AU - Jones, Alan
AU - Kazmierski, John
AU - Khan, Waqar
AU - Kneller, G. Larsen
AU - Labroo, Ajay
AU - Jaffe, Brian
AU - Lebenthal, Mark
AU - Lee, Daniel
AU - Ahmadian, Homayoun Reza
AU - Maccaro, Paul
AU - Mayer, Nolan
AU - McLaughlin, Paul
AU - Kwan, Tak W.
AU - Harnick, David
N1 - Funding Information:
Dr Steinberg reports significant research support from Janssen and consulting from BMS-Pfizer. Mr Shrader, Dr Pieper, Dr Thomas, and Dr Singer report no disclosures. Dr Allen has received grants from the American Heart Association, the National Institutes of Health, and the Patient-Centered Outcomes Research Institute; and has received consultancy fees from Janssen, Novartis, ZS Pharma, and St. Jude Medical. Dr Ansell reports modest Consultant/Advisory Board support from Bristol Myers Squibb, Pfizer, Janssen, Daiichi, Boehringer Ingelheim, and Alere. Dr Chan has received research support from the National Heart, Lung, and Blood Institute. Dr Ezekowitz reports serving as a consultant for AstraZeneca, Eisai, Pozen Inc, Boehringer Ingelheim, ARYx Therapeutics, Pfizer, Sanofi, Bristol-Myers Squibb, Portola, Daiichi Sanko, Medtronic, Merck, Johnson & Johnson, Gilead, Janssen Scientific Affairs, and Armetheon; and received grants from Boehringer Ingelheim, Bayer, Daiichi Sanko, Pfizer, and Bristol-Myers Squibb. Dr Freeman has acted as a consultant and advisory board member for Janssen Scientific; he also reports personal fees from Janssen Pharmaceuticals and the American College of Cardiology National Cardiovascular Data Registry outside the submitted work. Dr Fonarow reports modest Consultant/ Advisory Board support from Ortho McNeil. Dr Gersh reports modest DSMB/Advisory Board support from Medtronic, Baxter Healthcare Corporation, InspireMD, Cardiovascular Research Foundation, PPD Development, LP, Boston Scientific, and St. Jude. Dr Kowey reports modest Consultant/Advisory Board support from Boehringer Ingelheim, Bristol-Myers Squibb, Johnson & Johnson, Portola, Merck, Sanofi, and Daiichi Sankyo. Dr Mahaffey reports research support from Afferent, Amgen, Apple, AstraZeneca, Cardiva Medical, Inc., Daiichi, Ferrings, Google (Verily), Johnson & Johnson, Luitpold, Medtronic, Merck, Novartis, Sanofi, St. Jude, and Tenas; consulting to Ablynx, AstraZeneca, Boehringer Ingelheim, Bristol Meyers Squibb, Cardiometabolic Health Congress, Elsevier, Glaxo Smith Kline, Johnson & Johnson, Mederg, Medscape, Merck, Mitsubishi, Myokaria, Novartis, Oculeve, Portola, Radiometer, Springer Publishing, Theravance, UCSF, and WebMD; and equity in BioPrint Fitness. Dr Naccarelli reports research support from Janssen and service as consultant to Glaxo-Smith-Kline, Janssen, and Daiichi-Sankyo. Dr Reiffel reports research support from Janssen and Medtronic; was a consultant to Medtronic, Janssen, In Cardia Therapeutics, Acesion, Portola; and speaker’s bureau activities with Janssen and Boehringer Ingelheim. Dr Peterson reports significant research grant support from Eli Lilly & Company, Janssen Pharmaceuticals, Inc, and the American Heart Association; modest Consultant/ Advisory Board support from Boehringer Ingelheim, Bristol-Myers Squibb, Janssen Pharmaceuticals, Inc, Pfizer, and Genentech Inc. Dr Piccini reports significant research grant support from Johnson & Johnson/Janssen Pharmaceuticals; significant other research support from Bayer HealthCare Pharmaceuticals Inc (formerly Berlex Labs), Boston Scientific Corporation, Johnson & Johnson Pharmaceutical Research & Development; modest Consultant/Advisory Board support from Forest Laboratories, Inc and Medtronic, Inc; and
Publisher Copyright:
© 2018 The Authors.
PY - 2018/2/1
Y1 - 2018/2/1
N2 - 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 labelingin only555patients (43%).Compared with thosewhoseNOACdosewasappropriately 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-doseNOACs 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.
AB - 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 labelingin only555patients (43%).Compared with thosewhoseNOACdosewasappropriately 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-doseNOACs 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.
KW - Atrial fibrillation
KW - Dosing
KW - Non-vitamin K antagonist oral anticoagulant
KW - Outcome
UR - http://www.scopus.com/inward/record.url?scp=85042150633&partnerID=8YFLogxK
U2 - 10.1161/JAHA.117.007633
DO - 10.1161/JAHA.117.007633
M3 - Article
C2 - 29453305
AN - SCOPUS:85042150633
SN - 2047-9980
VL - 7
JO - Journal of the American Heart Association
JF - Journal of the American Heart Association
IS - 4
M1 - e007633
ER -