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      Outcomes Associated With Oral Anticoagulants Plus Antiplatelets in Patients With Newly Diagnosed Atrial Fibrillation

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          Key Points

          Question

          What outcomes are associated with combination therapy using oral anticoagulants (OAC) plus antiplatelet drugs in patients with newly diagnosed atrial fibrillation?

          Findings

          This cohort study of 24 436 patients with de novo atrial fibrillation found that, after adjusting for baseline characteristics and comedications, patients treated with OAC plus antiplatelet drugs had significantly higher incidence rates of stroke and any bleeding event than those receiving OAC alone. Use of OAC plus antiplatelet drugs was not associated with reduced risk of experiencing acute coronary syndromes.

          Meaning

          These findings suggest that patients with atrial fibrillation treated with OAC plus antiplatelet drugs may have significantly higher risk of stroke and bleeding compared with those receiving OAC alone.

          Abstract

          This cohort study compares outcomes of treatment with oral anticoagulants plus antiplatelet drugs vs oral anticoagulants alone in patients with newly diagnosed atrial fibrillation.

          Abstract

          Importance

          Patients with nonvalvular atrial fibrillation at risk of stroke should receive oral anticoagulants (OAC). However, approximately 1 in 8 patients in the Global Anticoagulant Registry in the Field (GARFIELD-AF) registry are treated with antiplatelet (AP) drugs in addition to OAC, with or without documented vascular disease or other indications for AP therapy.

          Objective

          To investigate baseline characteristics and outcomes of patients who were prescribed OAC plus AP therapy vs OAC alone.

          Design, Setting, and Participants

          Prospective cohort study of the GARFIELD-AF registry, an international, multicenter, observational study of adults aged 18 years and older with recently diagnosed nonvalvular atrial fibrillation and at least 1 risk factor for stroke enrolled between March 2010 and August 2016. Data were extracted for analysis in October 2017 and analyzed from April 2018 to June 2019.

          Exposure

          Participants received either OAC plus AP or OAC alone.

          Main Outcomes and Measures

          Clinical outcomes were measured over 3 and 12 months. Outcomes were adjusted for 40 covariates, including baseline conditions and medications.

          Results

          A total of 24 436 patients (13 438 [55.0%] male; median [interquartile range] age, 71 [64-78] years) were analyzed. Among eligible patients, those receiving OAC plus AP therapy had a greater prevalence of cardiovascular indications for AP, including acute coronary syndromes (22.0% vs 4.3%), coronary artery disease (39.1% vs 9.8%), and carotid occlusive disease (4.8% vs 2.0%). Over 1 year, patients treated with OAC plus AP had significantly higher incidence rates of stroke (adjusted hazard ratio [aHR], 1.49; 95% CI, 1.01-2.20) and any bleeding event (aHR, 1.41; 95% CI, 1.17-1.70) than those treated with OAC alone. These patients did not show evidence of reduced all-cause mortality (aHR, 1.22; 95% CI, 0.98-1.51). Risk of acute coronary syndrome was not reduced in patients taking OAC plus AP compared with OAC alone (aHR, 1.16; 95% CI, 0.70-1.94). Patients treated with OAC plus AP also had higher rates of all clinical outcomes than those treated with OAC alone over the short term (3 months).

          Conclusions and Relevance

          This study challenges the practice of coprescribing OAC plus AP unless there is a clear indication for adding AP to OAC therapy in newly diagnosed atrial fibrillation.

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          Most cited references44

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          World Medical Association Declaration of Helsinki: ethical principles for medical research involving human subjects.

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            2018 ESC/EACTS Guidelines on myocardial revascularization

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              2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS.

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                Author and article information

                Journal
                JAMA Netw Open
                JAMA Netw Open
                JAMA Netw Open
                JAMA Network Open
                American Medical Association
                2574-3805
                26 February 2020
                February 2020
                26 February 2020
                : 3
                : 2
                : e200107
                Affiliations
                [1 ]Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, United Kingdom
                [2 ]Aetion Inc, New York, New York
                [3 ]Cardiology Clinical Academic Group Molecular & Clinical Sciences Research Institute, St George's University of London, London, United Kingdom
                [4 ]Thrombosis Research Institute, London, United Kingdom
                [5 ]University of Besançon, Besançon, France
                [6 ]University of Warwick Medical School, Coventry, United Kingdom
                [7 ]Mayo Clinic College of Medicine, Rochester, Minnesota
                [8 ]Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts
                [9 ]Tokai University, Isehara, Japan
                [10 ]Formerly Department of Medicine, Technical University of Munich, Munich, Germany
                [11 ]Bayer HealthCare Pharmaceuticals, Berlin, Germany
                [12 ]Duke University, Durham, North Carolina
                [13 ]McMaster University, Hamilton, Ontario, Canada
                [14 ]Onze Lieve Vrouwe Gasthuis (OLVG), Amsterdam, the Netherlands
                [15 ]University College London, London, United Kingdom
                Author notes
                Article Information
                Accepted for Publication: January 5, 2020.
                Published: February 26, 2020. doi:10.1001/jamanetworkopen.2020.0107
                Open Access: This is an open access article distributed under the terms of the CC-BY License. © 2020 Fox KAA et al. JAMA Network Open.
                Corresponding Author: Keith A. A. Fox, MBChB, BHF Centre for Cardiovascular Science, University of Edinburgh, Queen’s Medical Research Institute, 47 Little France Crescent, Edinburgh EH16 4TJ, United Kingdom ( k.a.a.fox@ 123456ed.ac.uk ).
                Author Contributions: Dr Fox had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.
                Concept and design: Fox, Camm, Fitzmaurice, Goldhaber, Haas, Misselwitz, Pieper, Verheugt, Kakkar.
                Acquisition, analysis, or interpretation of data: Fox, Velentgas, Camm, Bassand, Gersh, Goto, Pieper, Turpie, Dabrowski, Luo, Gibbs.
                Drafting of the manuscript: Fox, Velentgas, Camm, Dabrowski.
                Critical revision of the manuscript for important intellectual content: Fox, Velentgas, Camm, Bassand, Fitzmaurice, Gersh, Goldhaber, Goto, Haas, Misselwitz, Pieper, Turpie, Verheugt, Luo, Gibbs, Kakkar.
                Statistical analysis: Velentgas, Dabrowski, Luo, Gibbs.
                Obtained funding: Misselwitz, Kakkar.
                Administrative, technical, or material support: Bassand, Fitzmaurice, Pieper.
                Supervision: Fox, Goto, Haas, Verheugt.
                Conflict of Interest Disclosures: Dr Fox reported receiving grants and personal fees from Bayer during the conduct of the study and grants from AstraZeneca, personal fees from Sanofi/Regeneron, and personal fees from Verseon outside the submitted work. Dr Velentgas reported receiving grants from Bayer during the conduct of the study. Dr Camm reported receiving grants and personal fees from Bayer, Boehringer Ingelheim, Daiichi Sankyo, and Pfizer BMS Alliance outside the submitted work. Dr Fitzmaurice reported receiving grants from the University of Warwick during the conduct of the study. Dr Goldhaber reported receiving grants from Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Boston Scientific’s BTG EKOS, Daiichi Sankyo, Janssen, and the National Heart, Lung, and Blood Institute and consulting fees from Bayer and Boehringer Ingelheim outside the submitted work. Dr Goto reported receiving personal fees from the Thrombosis Research Institute during the conduct of the study. Dr Haas reported receiving personal fees from Aspen, Bayer, Daiichi Sankyo, Bristol-Myers Squibb/Pfizer, and Portola outside the submitted work. Dr Turpie reported receiving personal fees from the Thrombosis Research Institute during the conduct of the study and personal fees from Janssen and Portola outside the submitted work. Dr Verheugt reported receiving personal fees from Bayer, Daiichi Sankyo, Boehringer Ingelheim, and Bristol-Meyers Squibb/Pfizer during the conduct of the study. Ms Dabrowski reported receiving personal fees from Aetion, Inc during the conduct of the study. Ms Luo reported receiving personal fees from Aetion, Inc during the conduct of the study. Ms Gibbs reported receiving personal fees from Aetion, Inc during the conduct of the study. Dr Kakkar reported receiving grants and personal fees from Bayer AG during the conduct of the study and personal fees from Bayer AG, Boehringer Ingelheim, Daiichi Sankyo, Janssen, Sanofi, and Verseon outside the submitted work. No other disclosures were reported.
                Funding/Support: The GARFIELD-AF Registry is an independent academic research initiative sponsored by the Thrombosis Research Institute (TRI; London, United Kingdom) and supported by an unrestricted research grant from Bayer Pharma AG (Berlin, Germany).
                Role of the Funder/Sponsor: The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.
                Group Information: See the eAppendix in the Supplement.
                Additional Contributions: We thank the physicians, nurses, and patients involved in the GARFIELD-AF registry. Martin van Eickels, MD (Bayer HealthCare Pharmaceuticals, Berlin, Germany), contributed to the study design. Medical writing support was provided by Alex Kahney, BSc (Thrombosis Research Institute, London, United Kingdom). Neither were compensated beyond their regular salaries.
                Article
                zoi200012
                10.1001/jamanetworkopen.2020.0107
                7137686
                32101311
                1992d65e-8226-41d2-82f5-29bb83a6e1ea
                Copyright 2020 Fox KAA et al. JAMA Network Open.

                This is an open access article distributed under the terms of the CC-BY License.

                History
                : 31 October 2019
                : 5 January 2020
                Categories
                Research
                Original Investigation
                Online Only
                Cardiology

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