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      Patients with atrial fibrillation and outcomes of cerebral infarction in those with treatment of warfarin versus no warfarin with references to CHA 2DS 2-VASc score, age and sex - A Swedish nationwide observational study with 48 433 patients

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          Abstract

          Aims

          There is controversy in the guidelines as to whether patients with atrial fibrillation and a low risk of stroke should be treated with anticoagulation, especially those with a CHA 2DS 2-VASc score of 1 point.

          Methods

          In a retrospective, nationwide cohort study, we used the Swedish National Patient Registry, the National Prescribed Drugs Registry, the Swedish Registry of Education and the Population and Housing Census Registry. 48 433 patients were identified between 1 January 2006 and 31 December 2008 with incident atrial fibrillation who were divided in age categories, sex and a CHA 2DS 2-VASc score of 0, 1, 2 and ≥3 and they were included in a time-varying analysis of warfarin treatment versus no treatment. The primary end-point was cerebral infarction and stroke, and patients were followed until 31 December 2009.

          Results

          Patients with 1 point from the CHA 2DS 2-VASc score showed the following adjusted hazard ratios (HR) with a 95% confidence interval: men 65–74 years 0.46 (0.25–0.83), men <65 years 1.11 (0.56–2.23) and women <65 years 2.13 (0.94–4.82), where HR <1 indicates protection with warfarin. In patients <65 years and 2 points, HR in men was 0.35 (0.18–0.69) and in women 1.84 (0.86–3.94) while, in women with at least 3 points, HR was 0.31 (0.16–0.59). In patients 65–74 years and 2 points, HR in men was 0.37 (0.23–0.59) and in women 0.39 (0.21–0.73). Categories including age ≥65 years or ≥3 points showed a statistically significant protection from warfarin.

          Conclusions

          Our results support that treatment with anticoagulation may be considered in all patients with an incident atrial fibrillation diagnosis and an age of 65 years and older, i.e. also when the CHA 2DS 2-VASc score is 1.

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          Most cited references13

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          All-cause mortality in 272 186 patients hospitalized with incident atrial fibrillation 1995–2008: a Swedish nationwide long-term case–control study

          Aims To evaluate long-term all-cause risk of mortality in women and men hospitalized for the first time with atrial fibrillation (AF) compared with matched controls. Methods and results A total of 272 186 patients (44% women) ≤85 years at the time of hospitalization with incidental AF 1995–2008 and 544 344 matched controls free of in-hospital diagnosis of AF were identified. Patients were followed via record linkage of the Swedish National Patient Registry and the Cause of Death Registry. Using Cox regression models, the long-term relative all-cause mortality risk, adjusted for concomitant diseases, in women vs. controls was 2.15, 1.72, and 1.44 (P < 0.001) in the age categories ≤65, 65–74, and 75–85 years, respectively. The corresponding figures for men were 1.76, 1.36, and 1.24 (P < 0.001). Among concomitant diseases, neoplasm, chronic renal failure, and chronic obstructive pulmonary disease contributed most to the increased all-cause mortality vs. controls. In patients with AF as the primary diagnosis, the relative risk of mortality was 1.63, 1.46, and 1.28 (P < 0.001) in women and 1.45, 1.17, and 1.10 (P < 0.001) in men. Conclusion Atrial fibrillation was an independent risk factor of all-cause mortality in patients with incident AF. The concomitant diseases that contributed most were found outside the thromboembolic risk scores. The highest relative risk of mortality was seen in women and in the youngest patients compared with controls, and the differences between genders in each age category were statistically significant.
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            2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS.

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              Identifying patients at high risk for stroke despite anticoagulation: a comparison of contemporary stroke risk stratification schemes in an anticoagulated atrial fibrillation cohort.

              The risk of stroke in patients with atrial fibrillation (AF) is not homogeneous, and various clinical risk factors have informed the development of stroke risk stratification schemes (RSS). Among anticoagulated cohorts, the emphasis should be on the identification of patients who remain at high risk for stroke despite anticoagulation. We investigated predictors of thromboembolism (TE) risk in an anticoagulated AF clinical trial cohort (n = 7329 subjects) and tested the predictive value of contemporary RSS in this cohort: CHADS₂, Framingham, NICE 2006, American College of Cardiology/American Heart Association/European Society of Cardiology 2006, the 8th American College of Chest Physicians guidelines and the CHA₂DS₂-VASc schemes. On multivariate analysis, significant predictors of TE were stroke/TIA (hazard ratio [HR], 2.24; P < 0.001), age 75 years or older (HR, 1.77; P = 0.0002), coronary artery disease (HR, 1.52; P = 0.0047), and smoking (HR, 2.10; P = 0.0005), whereas reported alcohol use (HR, 0.70; P = 0.02) was protective. Comparison of contemporary RSS demonstrated variable classification of AF patients into risk strata, although c-statistics for TE were broadly similar among the RSS tested and varied between 0.575 (NICE 2006) and 0.647 (CHA₂DS₂-VASc). CHA₂DS₂-VASc classified 94.2% as being at high risk, whereas most other RSS categorized two-thirds as being at high risk. Of the 184 TE events, 181 (98.4%) occurred in patients identified as being at high risk by the CHA₂DS₂-VASc schema. There was a stepwise increase in TE with increasing CHA₂DS₂-VASc score (P (trend) < 0.0001), which had the highest HR (3.75) among the tested schemes. The negative predictive value (ie, the percent categorized as "not high risk" actually being free from TE) for CHA₂DS₂-VASc was 99.5%. Coronary artery disease and smoking are additional risk factors for TE in anticoagulated AF patients, whereas alcohol use appears protective. Of the contemporary stroke RSS, the CHA₂DS₂-VASc scheme correctly identified the greatest proportion of AF patients at high risk, despite the similar predictive ability of most RSS evidenced by the c-statistic.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                4 May 2017
                2017
                : 12
                : 5
                : e0176846
                Affiliations
                [1 ]Department of Cardiology, Faculty of Health, Örebro University, Örebro, Sweden
                [2 ]Clinical Epidemiology and Biostatistics, School of Medical Sciences, Örebro University, Örebro, Sweden
                [3 ]Department of Occupational and Environmental Medicine, Örebro University, Örebro, Sweden
                [4 ]Department of Medical Science, Uppsala University, Uppsala, Sweden
                [5 ]Sahlgrenska Academy at Sahlgrenska University Hospital, Göteborg, Sweden
                University of Bologna, ITALY
                Author notes

                Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: KMH is a former employee of AstraZeneca R&D. This does not alter our adherence to PLOS ONE policies on sharing data and materials. The other authors have declared that no competing interests exist.

                • Conceptualization: TA AM IB OF KMH NE DP.

                • Formal analysis: TA AM IB.

                • Writing – original draft: TA.

                • Writing – review & editing: TA AM IB OF KMH NE DP.

                Author information
                http://orcid.org/0000-0001-5055-3728
                Article
                PONE-D-16-50301
                10.1371/journal.pone.0176846
                5417522
                28472091
                b34f8f68-23fc-42c2-9d52-dafce4fa7bcd
                © 2017 Andersson 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
                : 20 December 2016
                : 18 April 2017
                Page count
                Figures: 7, Tables: 5, Pages: 17
                Funding
                Funded by: Research committee of Orebro University
                Award ID: OLL 2012-265231
                Award Recipient :
                The study was supported by a grant from the Research Committee of örebro University (OLL 2012-265231), AstraZeneca R&D Mölndal and the örebro Heart Foundation. AstraZeneca provided support in the form of salary for one author [KMH, at the time an employee of AstraZeneca] but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of the authors are articulated in the author contribution section.
                Categories
                Research Article
                Medicine and Health Sciences
                Cardiology
                Arrhythmia
                Atrial Fibrillation
                Medicine and Health Sciences
                Neurology
                Cerebrovascular Diseases
                Stroke
                Medicine and Health Sciences
                Vascular Medicine
                Stroke
                Medicine and Health Sciences
                Diagnostic Medicine
                Signs and Symptoms
                Infarction
                Medicine and Health Sciences
                Pathology and Laboratory Medicine
                Signs and Symptoms
                Infarction
                Medicine and Health Sciences
                Diagnostic Medicine
                Signs and Symptoms
                Hemorrhage
                Medicine and Health Sciences
                Pathology and Laboratory Medicine
                Signs and Symptoms
                Hemorrhage
                Medicine and Health Sciences
                Vascular Medicine
                Hemorrhage
                Medicine and Health Sciences
                Pulmonology
                Chronic Obstructive Pulmonary Disease
                Medicine and Health Sciences
                Nephrology
                Renal Failure
                Medicine and Health Sciences
                Oncology
                Cancers and Neoplasms
                Neoplasms
                People and Places
                Population Groupings
                Ethnicities
                Swedes
                Custom metadata
                All relevant data are within the paper.

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