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      Global Oral Anticoagulation Use Varies by Region in Patients With Recent Diagnosis of Atrial Fibrillation: The GLORIA‐AF Phase III Registry

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          Abstract

          Background

          Effective stroke prevention with oral anticoagulants (OAC) is recommended for some patients with atrial fibrillation (AF). We aimed to describe OAC use by geographical region and type of site in patients with recent‐onset AF enrolled in a large global registry.

          Methods and Results

          Eligible participants were recruited into GLORIA‐AF (Global Registry on Long‐Term Oral Antithrombotic Treatment in Patients With Atrial Fibrillation), a prospective observational cohort study from 2014 to 2016 in 4 international regions: North America, Europe, Asia, and Latin America. Cumulative incidence functions were generated for direct OACs (DOAC), vitamin K antagonists, and antiplatelet drugs considering competing risks, stratified by region and type of site. Time‐to‐treatment initiation after AF diagnosis was analyzed with Fine‐Gray subdistribution hazard models. A total of 21 237 patients eligible for analysis were identified. By 30 days after AF diagnosis, 40%, 16%, and 8.6% of patients had DOAC, vitamin K antagonists, and antiplatelet drugs initiated, respectively. Earlier initiation of DOACs was observed in Europe, with Asia and Latin America having lower hazard rates of DOAC time‐to‐treatment initiation than Europe (hazard ratio [HR], 0.66; 95% CI, 0.62–0.70 and HR, 0.79; 95% CI, 0.73–0.85, respectively). DOAC initiation was highest in community hospitals, vitamin K antagonists in outpatient health care centers/anticoagulation clinics, and antiplatelet drugs in primary care clinics.

          Conclusions

          Important geographic variability exists with the use of OACs for patients with AF. Differences in the time‐to‐treatment initiation of OAC by type of site suggests suboptimal implementation of guideline recommendations and could result in less benefit and more harm. Optimizing OAC use for patients with AF may improve outcomes and reduce health care costs.

          Registration

          URL: http://www.clinicaltrials.gov; Unique identifiers: NCT01468701, NCT01671007.

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          Most cited references38

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            An Introduction to Propensity Score Methods for Reducing the Effects of Confounding in Observational Studies

            The propensity score is the probability of treatment assignment conditional on observed baseline characteristics. The propensity score allows one to design and analyze an observational (nonrandomized) study so that it mimics some of the particular characteristics of a randomized controlled trial. In particular, the propensity score is a balancing score: conditional on the propensity score, the distribution of observed baseline covariates will be similar between treated and untreated subjects. I describe 4 different propensity score methods: matching on the propensity score, stratification on the propensity score, inverse probability of treatment weighting using the propensity score, and covariate adjustment using the propensity score. I describe balance diagnostics for examining whether the propensity score model has been adequately specified. Furthermore, I discuss differences between regression-based methods and propensity score-based methods for the analysis of observational data. I describe different causal average treatment effects and their relationship with propensity score analyses.
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              Rivaroxaban versus warfarin in nonvalvular atrial fibrillation.

              The use of warfarin reduces the rate of ischemic stroke in patients with atrial fibrillation but requires frequent monitoring and dose adjustment. Rivaroxaban, an oral factor Xa inhibitor, may provide more consistent and predictable anticoagulation than warfarin. In a double-blind trial, we randomly assigned 14,264 patients with nonvalvular atrial fibrillation who were at increased risk for stroke to receive either rivaroxaban (at a daily dose of 20 mg) or dose-adjusted warfarin. The per-protocol, as-treated primary analysis was designed to determine whether rivaroxaban was noninferior to warfarin for the primary end point of stroke or systemic embolism. In the primary analysis, the primary end point occurred in 188 patients in the rivaroxaban group (1.7% per year) and in 241 in the warfarin group (2.2% per year) (hazard ratio in the rivaroxaban group, 0.79; 95% confidence interval [CI], 0.66 to 0.96; P<0.001 for noninferiority). In the intention-to-treat analysis, the primary end point occurred in 269 patients in the rivaroxaban group (2.1% per year) and in 306 patients in the warfarin group (2.4% per year) (hazard ratio, 0.88; 95% CI, 0.74 to 1.03; P<0.001 for noninferiority; P=0.12 for superiority). Major and nonmajor clinically relevant bleeding occurred in 1475 patients in the rivaroxaban group (14.9% per year) and in 1449 in the warfarin group (14.5% per year) (hazard ratio, 1.03; 95% CI, 0.96 to 1.11; P=0.44), with significant reductions in intracranial hemorrhage (0.5% vs. 0.7%, P=0.02) and fatal bleeding (0.2% vs. 0.5%, P=0.003) in the rivaroxaban group. In patients with atrial fibrillation, rivaroxaban was noninferior to warfarin for the prevention of stroke or systemic embolism. There was no significant between-group difference in the risk of major bleeding, although intracranial and fatal bleeding occurred less frequently in the rivaroxaban group. (Funded by Johnson & Johnson and Bayer; ROCKET AF ClinicalTrials.gov number, NCT00403767.).
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                Author and article information

                Contributors
                gregory.lip@liverpool.ac.uk
                Journal
                J Am Heart Assoc
                J Am Heart Assoc
                10.1002/(ISSN)2047-9980
                JAH3
                ahaoa
                Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease
                John Wiley and Sons Inc. (Hoboken )
                2047-9980
                04 March 2022
                15 March 2022
                : 11
                : 6 ( doiID: 10.1002/jah3.v11.6 )
                : e023907
                Affiliations
                [ 1 ] Biostatistics and Data Sciences Boehringer Ingelheim Pharmaceuticals Inc. Ridgefield CT
                [ 2 ] Liverpool Centre for Cardiovascular Science University of Liverpool and Liverpool Heart & Chest Hospital Liverpool United Kingdom
                [ 3 ] Department of Emergency Medicine School of Medicine Oregon Health & Science University Portland OR
                [ 4 ] Department of Clinical Development and Medical Affairs Therapeutic Area Cardiometabolism Boehringer Ingelheim International GmbH Ingelheim Germany
                [ 5 ] MercyOne North Iowa Mason City IA
                [ 6 ] Department of Thrombosis and Hemostasis Leiden University Medical Center Leiden Netherlands
                [ 7 ] University of Iowa Hospitals and Clinics Iowa City IA
                Author notes
                [*] [* ] Correspondence to: Gregory Y. H. Lip, MD, Liverpool Centre for Cardiovascular Science, Institute of Life Course & Medical Sciences, William Henry Duncan Building, 6 West Derby Street, Liverpool L7 8TX, United Kingdom. Email: gregory.lip@ 123456liverpool.ac.uk

                [*]

                V. Bayer, A. Kotalczyk, and B. Kea are joint first authors.

                [ † ]

                M. V. Huisman and G. Y. H. Lip are co‐chairs of the GLORIA‐AF registry and are joint senior authors with B. Olshansky.

                Author information
                https://orcid.org/0000-0003-0527-4310
                https://orcid.org/0000-0002-6762-3187
                https://orcid.org/0000-0002-9719-5988
                https://orcid.org/0000-0002-8494-2876
                https://orcid.org/0000-0003-1423-5348
                https://orcid.org/0000-0002-7566-1626
                https://orcid.org/0000-0002-6044-045X
                Article
                JAH37204
                10.1161/JAHA.121.023907
                9075285
                35243870
                032b3127-4dfd-449d-84a7-7c1db2eeca8f
                © 2022 The Authors and Boehringer Ingelheim. Published on behalf of the American Heart Association, Inc., by Wiley.

                This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

                History
                : 13 September 2021
                : 06 January 2022
                Page count
                Figures: 1, Tables: 4, Pages: 35, Words: 10624
                Funding
                Funded by: Boehringer Ingelheim , doi 10.13039/100001003;
                Categories
                Original Research
                Original Research
                Arrhythmia and Electrophysiology
                Custom metadata
                2.0
                March 15, 2022
                Converter:WILEY_ML3GV2_TO_JATSPMC version:6.1.2 mode:remove_FC converted:15.03.2022

                Cardiovascular Medicine
                atrial fibrillation,direct‐acting oral anticoagulants,oral anticoagulation,stroke prevention,vitamin k antagonists

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