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      Thromboembolic events and vascular dementia in patients with atrial fibrillation and low apparent stroke risk

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          Abstract

          The prevention of thromboembolism in atrial fibrillation (AF) is typically restricted to patients with specific risk factors and ignores outcomes such as vascular dementia. This population-based cohort study used electronic healthcare records from 5,199,994 primary care patients (UK; 2005–2020). A total of 290,525 (5.6%) had a diagnosis of AF and were aged 40–75 years, of which 36,340 had no history of stroke, a low perceived risk of stroke based on clinical risk factors and no oral anticoagulant prescription. Matching was performed for age, sex and region to 117,298 controls without AF. During 5 years median follow-up (831,005 person-years), incident stroke occurred in 3.8% with AF versus 1.5% control (adjusted hazard ratio (HR) 2.06, 95% confidence interval (CI) 1.91–2.21; P < 0.001), arterial thromboembolism 0.3% versus 0.1% (HR 2.39, 95% CI 1.83–3.11; P < 0.001), and all-cause mortality 8.9% versus 5.0% (HR 1.44, 95% CI 1.38–1.50; P < 0.001). AF was associated with all-cause dementia (HR 1.17, 95% CI 1.04–1.32; P = 0.010), driven by vascular dementia (HR 1.68, 95% CI 1.33–2.12; P < 0.001) rather than Alzheimer’s disease (HR 0.85, 95% CI 0.70–1.03; P = 0.09). Death and thromboembolic outcomes, including vascular dementia, are substantially increased in patients with AF despite a lack of conventional stroke risk factors.

          Abstract

          Atrial fibrillation is associated with an increased risk of thromboembolic events and vascular dementia in patients with no previous history of stroke or any conventional risk factors, compared to patients without atrial fibrillation.

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            Comparison of the efficacy and safety of new oral anticoagulants with warfarin in patients with atrial fibrillation: a meta-analysis of randomised trials.

            Four new oral anticoagulants compare favourably with warfarin for stroke prevention in patients with atrial fibrillation; however, the balance between efficacy and safety in subgroups needs better definition. We aimed to assess the relative benefit of new oral anticoagulants in key subgroups, and the effects on important secondary outcomes. We searched Medline from Jan 1, 2009, to Nov 19, 2013, limiting searches to phase 3, randomised trials of patients with atrial fibrillation who were randomised to receive new oral anticoagulants or warfarin, and trials in which both efficacy and safety outcomes were reported. We did a prespecified meta-analysis of all 71,683 participants included in the RE-LY, ROCKET AF, ARISTOTLE, and ENGAGE AF-TIMI 48 trials. The main outcomes were stroke and systemic embolic events, ischaemic stroke, haemorrhagic stroke, all-cause mortality, myocardial infarction, major bleeding, intracranial haemorrhage, and gastrointestinal bleeding. We calculated relative risks (RRs) and 95% CIs for each outcome. We did subgroup analyses to assess whether differences in patient and trial characteristics affected outcomes. We used a random-effects model to compare pooled outcomes and tested for heterogeneity. 42,411 participants received a new oral anticoagulant and 29,272 participants received warfarin. New oral anticoagulants significantly reduced stroke or systemic embolic events by 19% compared with warfarin (RR 0·81, 95% CI 0·73-0·91; p<0·0001), mainly driven by a reduction in haemorrhagic stroke (0·49, 0·38-0·64; p<0·0001). New oral anticoagulants also significantly reduced all-cause mortality (0·90, 0·85-0·95; p=0·0003) and intracranial haemorrhage (0·48, 0·39-0·59; p<0·0001), but increased gastrointestinal bleeding (1·25, 1·01-1·55; p=0·04). We noted no heterogeneity for stroke or systemic embolic events in important subgroups, but there was a greater relative reduction in major bleeding with new oral anticoagulants when the centre-based time in therapeutic range was less than 66% than when it was 66% or more (0·69, 0·59-0·81 vs 0·93, 0·76-1·13; p for interaction 0·022). Low-dose new oral anticoagulant regimens showed similar overall reductions in stroke or systemic embolic events to warfarin (1·03, 0·84-1·27; p=0·74), and a more favourable bleeding profile (0·65, 0·43-1·00; p=0·05), but significantly more ischaemic strokes (1·28, 1·02-1·60; p=0·045). This meta-analysis is the first to include data for all four new oral anticoagulants studied in the pivotal phase 3 clinical trials for stroke prevention or systemic embolic events in patients with atrial fibrillation. New oral anticoagulants had a favourable risk-benefit profile, with significant reductions in stroke, intracranial haemorrhage, and mortality, and with similar major bleeding as for warfarin, but increased gastrointestinal bleeding. The relative efficacy and safety of new oral anticoagulants was consistent across a wide range of patients. Our findings offer clinicians a more comprehensive picture of the new oral anticoagulants as a therapeutic option to reduce the risk of stroke in this patient population. None. Copyright © 2014 Elsevier Ltd. All rights reserved.
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              Global epidemiology of atrial fibrillation: An increasing epidemic and public health challenge

              Atrial fibrillation is the most frequent cardiac arrhythmia. It has been estimated that 6–12 million people worldwide will suffer this condition in the US by 2050 and 17.9 million people in Europe by 2060. Atrial fibrillation is a major risk factor for ischemic stroke and provokes important economic burden along with significant morbidity and mortality. We provide here comprehensive and updated statistics on worldwide epidemiology of atrial fibrillation. An electronic search was conducted for atrial fibrillation. The epidemiologic information was retrieved from the Global Health Data Exchange database, which is regarded as one of the most comprehensive worldwide catalogs of surveys, censuses, vital statistics, and other health-related data. A total of 3.046 million new cases of atrial fibrillation worldwide were registered in the database during 2017. The estimated incidence rate for 2017 (403/millions inhabitants) was 31% higher than the corresponding incidence in 1997. The worldwide prevalence of atrial fibrillation is 37,574 million cases (0.51% of worldwide population), increased also by 33% during the last 20 years. The highest burden is seen in countries with high socio-demographic index, though the largest recent increased occurred in middle socio-demographic index countries. Future projections suggest that absolute atrial fibrillation burden may increase by >60% in 2050. Our analyses suggest that atrial fibrillation incidence and prevalence have increased over the last 20 years and will continue to increase over the next 30 years, especially in countries with middle socio-demographic index, becoming one of the largest epidemics and public health challenges.
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                Author and article information

                Contributors
                d.kotecha@bham.ac.uk
                Journal
                Nat Med
                Nat Med
                Nature Medicine
                Nature Publishing Group US (New York )
                1078-8956
                1546-170X
                5 June 2024
                5 June 2024
                2024
                : 30
                : 8
                : 2288-2294
                Affiliations
                [1 ]Institute of Cardiovascular Sciences, University of Birmingham, ( https://ror.org/03angcq70) Birmingham, UK
                [2 ]GRID grid.412563.7, ISNI 0000 0004 0376 6589, NIHR Birmingham Biomedical Research Centre, , University Hospitals Birmingham NHS Foundation Trust, ; Birmingham, UK
                [3 ]West Midlands NHS Secure Data Environment, University Hospitals Birmingham NHS Foundation Trust, ( https://ror.org/014ja3n03) Birmingham, UK
                [4 ]Institute of Applied Health Research, University of Birmingham, ( https://ror.org/03angcq70) Birmingham, UK
                [5 ]Clinical Practice Research Datalink, Medicines and Healthcare products Regulatory Agency, ( https://ror.org/01h3bmp72) London, UK
                [6 ]Patient and Public Involvement Team, Birmingham, UK
                [7 ]Primary Care Clinical Research, NIHR Clinical Research Network West Midlands, Birmingham, UK
                Author information
                http://orcid.org/0000-0003-0957-4185
                http://orcid.org/0000-0001-8875-7363
                http://orcid.org/0000-0002-5510-1306
                http://orcid.org/0000-0002-9703-8659
                http://orcid.org/0000-0001-6229-7477
                http://orcid.org/0000-0002-6816-1279
                http://orcid.org/0000-0002-2570-9812
                Article
                3049
                10.1038/s41591-024-03049-9
                11333279
                38839900
                9e9cc733-5f92-4968-92ef-8cf5d2cd5f41
                © The Author(s) 2024

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 26 October 2023
                : 7 May 2024
                Funding
                Funded by: FundRef https://doi.org/10.13039/501100000272, DH | National Institute for Health Research (NIHR);
                Award ID: NIHR203326
                Award ID: NIHR130280
                Award Recipient :
                Funded by: FundRef https://doi.org/10.13039/501100000265, RCUK | Medical Research Council (MRC);
                Award ID: HDRUK/CFC/01
                Award Recipient :
                Funded by: FundRef https://doi.org/10.13039/501100000274, British Heart Foundation (BHF);
                Award ID: Accelerator Birmingham
                Award ID: FS/CDRF/21/21032
                Award Recipient :
                Categories
                Article
                Custom metadata
                © Springer Nature America, Inc. 2024

                Medicine
                atrial fibrillation,stroke,dementia
                Medicine
                atrial fibrillation, stroke, dementia

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