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      Evolution of antithrombotic therapy for patients with atrial fibrillation: The prospective global GLORIA-AF registry program

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          Abstract

          Objective

          To assess baseline characteristics and antithrombotic treatment (ATT) prescription patterns in patients enrolled in the third phase of the GLORIA-AF Registry Program, evaluate predictors of treatment prescription, and compare results with phase II.

          Methods

          GLORIA-AF is a large, global, prospective registry program, enrolling patients with newly diagnosed nonvalvular atrial fibrillation (AF) at risk of stroke. Patients receiving dabigatran were followed for two years in phase II, and all patients were followed for 3 years in phase III. Phase II started when dabigatran became available; phase III started when the characteristics of patients receiving dabigatran became roughly comparable with those receiving vitamin K antagonists (VKAs).

          Results

          Between 2014 and 2016, 21,241 patients were enrolled in phase III. In total, 82% of patients were prescribed oral anticoagulation ([OAC]; 59.5% novel/nonvitamin K oral anticoagulants [NOACs], 22.7% VKAs). A further 11% of patients were prescribed antiplatelets without OAC and 7% were prescribed no ATT. A high stroke risk was the main driver of OAC prescription. Factors associated with prescription of VKA over NOAC included type of site, region, physician specialty, and impaired kidney function.

          Conclusion

          Over the past few years, data from phase III of GLORIA-AF show that OACs have become the standard treatment option, with most newly diagnosed AF patients prescribed a NOAC. However, in some regions a remarkable proportion of patients remain undertreated. In comparison with phase II, more patients received NOACs in phase III while the prescription of VKA decreased. VKAs were preferred over NOACs in patients with impaired kidney function.

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          Most cited references28

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          Multiple imputation using chained equations: Issues and guidance for practice

          Multiple imputation by chained equations is a flexible and practical approach to handling missing data. We describe the principles of the method and show how to impute categorical and quantitative variables, including skewed variables. We give guidance on how to specify the imputation model and how many imputations are needed. We describe the practical analysis of multiply imputed data, including model building and model checking. We stress the limitations of the method and discuss the possible pitfalls. We illustrate the ideas using a data set in mental health, giving Stata code fragments. 2010 John Wiley & Sons, Ltd.
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            2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS.

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              2019 AHA/ACC/HRS Focused Update of the 2014 AHA/ACC/HRS Guideline for the Management of Patients With Atrial Fibrillation

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                Author and article information

                Contributors
                Role: ConceptualizationRole: Writing – original draftRole: Writing – review & editing
                Role: Data curationRole: Formal analysisRole: ValidationRole: Writing – review & editing
                Role: Data curationRole: Formal analysisRole: ValidationRole: Writing – review & editing
                Role: Data curationRole: Formal analysisRole: ValidationRole: Writing – review & editing
                Role: ConceptualizationRole: MethodologyRole: Writing – original draftRole: Writing – review & editing
                Role: ConceptualizationRole: InvestigationRole: MethodologyRole: Writing – original draftRole: Writing – review & editing
                Role: ConceptualizationRole: Formal analysisRole: Funding acquisitionRole: MethodologyRole: Writing – original draftRole: Writing – review & editing
                Role: MethodologyRole: Writing – original draft
                Role: Writing – review & editing
                Role: MethodologyRole: Writing – review & editing
                Role: Writing – review & editing
                Role: Writing – review & editing
                Role: Writing – review & editing
                Role: Writing – review & editing
                Role: Writing – review & editing
                Role: Writing – review & editing
                Role: Writing – review & editing
                Role: Writing – review & editing
                Role: Editor
                Journal
                PLoS One
                PLoS One
                plos
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                6 October 2022
                2022
                : 17
                : 10
                : e0274237
                Affiliations
                [1 ] Charité–Universitätsmedizin Berlin, Berlin, Germany
                [2 ] Takeda Pharmaceuticals, Inc., Cambridge, Massachusetts, United States of America
                [3 ] Sanofi-Aventis Recherche et Développement, Chilly-Mazarin, France
                [4 ] Liverpool Centre for Cardiovascular Science, University of Liverpool and Liverpool Heart & Chest Hospital, Liverpool, United Kingdom
                [5 ] Department of Clinical Medicine, Aalborg Thrombosis Research Unit, Aalborg University, Aalborg, Denmark
                [6 ] Leiden University Medical Center, Leiden, the Netherlands
                [7 ] Department of CardioMetabolism and Respiratory Medicine, Boehringer Ingelheim International GmbH, Ingelheim, Germany
                [8 ] Icahn School of Medicine at Mount Sinai, New York City, New York, United States of America
                [9 ] University Hospital Essen, Essen, Germany
                [10 ] Boehringer Ingelheim, Burlington, Canada
                [11 ] Atrial Fibrillation Center, Beijing Anzhen Hospital, Beijing, People’s Republic of China
                [12 ] Hannover Medical School, Hannover, Germany
                [13 ] UCB Biosciences GmbH, Monheim, Germany
                [14 ] Clínica y Maternidad Suizo Argentina, Buenos Aires, Argentina
                [15 ] University Hospital Basel, Stroke Center Neurology, and University of Basel, Basel, Switzerland
                [16 ] Stiftung Institut, Ludwigshafen, Germany
                [17 ] RTI Health Solutions, Research Triangle Institute, Research Triangle Park, North Carolina, United States of America
                University of Messina, ITALY
                Author notes

                Competing Interests: L Beier declares no conflicts of interest at the time of manuscript writing and is now an employee of Novartis Pharma GmbH. S Lu was an employee of Boehringer Ingelheim at the time of manuscript writing and is now employed by Biogen Inc. S Marler, C Teutsch, K Zint, L Baker and M Paquette are employees of Boehringer Ingelheim. L Riou França was an employee of Boehringer Ingelheim at the time of manuscript writing and is now employed by Sanofi-Aventis. GYH Lip is a consultant and speaker for BMS/Pfizer, Boehringer Ingelheim and Daiichi-Sankyo. No fees are received personally. MV Huisman reports grants from ZonMW Dutch Healthcare Fund, grants and fees to the hospital from Boehringer Ingelheim, Pfizer-BMS, Bayer HealthCare, Aspen, Daiichi-Sankyo, outside the submitted work. JL Halperin has engaged in consulting activities with Boehringer Ingelheim, for advisory activities involving anticoagulants, and he is a member of the Executive Steering Committee of the GLORIA-AF Registry. H-C Diener has received honoraria for participation in clinical trials, contribution to advisory boards or oral presentations from: Abbott, Bayer Vital, Bristol-Myers Squibb (BMS), Boehringer Ingelheim, Daiichi-Sankyo, Medtronic, Pfizer, Portola, Sanofi-Aventis, and WebMD Global. Financial support for research projects was provided by Boehringer Ingelheim. Dr Diener chairs the Treatment Guidelines Committee of the German Society of Neurology and contributed to the EHRA and ESC guidelines for the treatment of AF. C-S Ma has received honoraria for lectures from AstraZeneca, Bayer HealthCare, Boehringer Ingelheim, BMS, Johnson & Johnson, and Pfizer. DB Bartels was an employee of Boehringer Ingelheim at time of manuscript writing and is now an employee at UCB Pharma GmbH. SJ Dubner has received consultancy fees for serving as a steering committee member for Boehringer Ingelheim; he also holds research grants from St Jude Medical. P Lyrer has received honoraria for contribution to advisory boards from Boehringer Ingelheim, BMS, Bayer, Pfizer, Daiichi Sankyo, and Ricordati, and research grants from the Swiss Heart Foundation, Swiss National Foundation, Bayer, Sanofi, Acticor, and the University Hospital Basel foundation (propatient). J Senges has received honoraria for contribution to advisory boards from Boehringer Ingelheim. KJ Rothman declares no conflicts of interest.

                ‡ MVH and GYHL are co-Chairs of the GLORIA-AF registry program and are joint senior authors with KJR.

                Author information
                https://orcid.org/0000-0003-1861-0635
                https://orcid.org/0000-0001-9449-9225
                Article
                PONE-D-21-27023
                10.1371/journal.pone.0274237
                9536607
                36201473
                b166b0cc-2dc9-4351-a77b-e44a3b2aef87
                © 2022 Beier et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 26 August 2021
                : 16 August 2022
                Page count
                Figures: 4, Tables: 2, Pages: 14
                Funding
                Funded by: funder-id http://dx.doi.org/10.13039/100008349, Boehringer Ingelheim;
                Award Recipient :
                This registry program was funded by Boehringer Ingelheim GmbH. Boehringer Ingelheim were involved in the study design, data collection and analysis, preparation of the manuscript and review for scientific accuracy. Authors had the final decision on content and the decision to publish; specific roles of each author are articulated in the “author contributions” section.
                Categories
                Research Article
                Medicine and Health Sciences
                Epidemiology
                Medical Risk Factors
                Medicine and Health Sciences
                Cardiology
                Arrhythmia
                Atrial Fibrillation
                Medicine and Health Sciences
                Medical Conditions
                Cardiovascular Diseases
                Cardiovascular Disease Risk
                Medicine and Health Sciences
                Cardiology
                Cardiovascular Medicine
                Cardiovascular Diseases
                Cardiovascular Disease Risk
                Medicine and Health Sciences
                Pharmaceutics
                Drug Therapy
                Antiplatelet Therapy
                Medicine and Health Sciences
                Medical Conditions
                Cerebrovascular Diseases
                Stroke
                Ischemic Stroke
                Medicine and Health Sciences
                Neurology
                Cerebrovascular Diseases
                Stroke
                Ischemic Stroke
                Medicine and Health Sciences
                Vascular Medicine
                Stroke
                Ischemic Stroke
                Medicine and Health Sciences
                Clinical Medicine
                Signs and Symptoms
                Hemorrhage
                Medicine and Health Sciences
                Vascular Medicine
                Hemorrhage
                Medicine and Health Sciences
                Pharmaceutics
                Drug Therapy
                Antiplatelet Therapy
                Oral Antiplatelet Therapy
                Medicine and Health Sciences
                Pharmaceutics
                Drug Therapy
                Cardiovascular Therapy
                Anticoagulant Therapy
                Custom metadata
                To ensure independent interpretation of clinical study results and enable authors to fulfill their role and obligations under the ICMJE criteria, Boehringer Ingelheim grants all external authors access to relevant clinical study data. In adherence with the Boehringer Ingelheim Policy on Transparency and Publication of Clinical Study Data, scientific and medical researchers can request access to clinical study data after publication of the primary manuscript in a peer-reviewed journal, regulatory activities are complete and other criteria are met. Researchers should use the https://vivli.org/ link to request access to study data and visit https://www.mystudywindow.com/msw/datasharing for further information.

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