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

Alastair R Mobley; Anuradhaa Subramanian; Asgher Champsi; Xiaoxia Wang; Puja Myles; Paul McGreavy; Karina V Bunting; David Shukla; Krishnarajah Nirantharakumar; Dipak Kotecha

doi:10.1038/s41591-024-03049-9

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

Alastair R Mobley, Anuradhaa Subramanian, Asgher Champsi, Xiaoxia Wang, Puja Myles, Paul McGreavy, Karina V Bunting, David Shukla, Krishnarajah Nirantharakumar, Dipak Kotecha^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

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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.

Original language	English
Journal	Nature Medicine
Early online date	5 Jun 2024
DOIs	https://doi.org/10.1038/s41591-024-03049-9
Publication status	E-pub ahead of print - 5 Jun 2024

Bibliographical note

Acknowledgements
The study staff are funded by the National Institute for Health and Care Research (NIHR Birmingham Biomedical Research Centre; NIHR203326; D.K.), MRC Health Data Research UK (HDRUK/CFC/01), NHS Data for R&D Subnational Secure Data Environment program (West Midlands; D.K.) and the British Heart Foundation Accelerator Award to the University of Birmingham (AA/18/2/34218). The DaRe2THINK trial is funded by the National Institute for Health and Care Research (NIHR130280; D.K. and D.S.), with medications funded by the NHS (UK Department of Health and Social Care). The opinions expressed in this paper are those of the authors and do not represent any of the listed organizations; none of the organizations had any role in design or conduct of the study (including collection, analysis and interpretation of the data) or any involvement in preparation, review or approval of the manuscript. The funders of the study had no role in study design, data collection, data analysis, data interpretation or writing of the report.

© 2024. The Author(s).

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10.1038/s41591-024-03049-9Licence: Creative Commons: Attribution (CC BY)

MobleyAR2024ThromboembolicFinal published version, 3.27 MBLicence: Creative Commons: Attribution (CC BY)

Preventing stroke, premature death and cognitive decline in a broader community of patients with atrial fibrillation using healthcare data for pragmatic research (DaRe2THINK)
Kotecha, D. (Principal Investigator), Shukla, D. (Researcher), Calvert, M. (Co-Investigator), Nirantharakumar, K. (Co-Investigator) & Gkoutos, G. (Co-Investigator)
NIHR EVALUATION, TRIALS AND STUDIES COORDINATING CENTRE, CRN: WEST MIDLANDS
1/12/20 → 30/11/25
Project: Other Government Departments

Cite this

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title = "Thromboembolic events and vascular dementia in patients with atrial fibrillation and low apparent stroke risk",

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.",

author = "Mobley, {Alastair R} and Anuradhaa Subramanian and Asgher Champsi and Xiaoxia Wang and Puja Myles and Paul McGreavy and Bunting, {Karina V} and David Shukla and Krishnarajah Nirantharakumar and Dipak Kotecha",

note = "Acknowledgements The study staff are funded by the National Institute for Health and Care Research (NIHR Birmingham Biomedical Research Centre; NIHR203326; D.K.), MRC Health Data Research UK (HDRUK/CFC/01), NHS Data for R&D Subnational Secure Data Environment program (West Midlands; D.K.) and the British Heart Foundation Accelerator Award to the University of Birmingham (AA/18/2/34218). The DaRe2THINK trial is funded by the National Institute for Health and Care Research (NIHR130280; D.K. and D.S.), with medications funded by the NHS (UK Department of Health and Social Care). The opinions expressed in this paper are those of the authors and do not represent any of the listed organizations; none of the organizations had any role in design or conduct of the study (including collection, analysis and interpretation of the data) or any involvement in preparation, review or approval of the manuscript. The funders of the study had no role in study design, data collection, data analysis, data interpretation or writing of the report. {\textcopyright} 2024. The Author(s).",

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AU - Subramanian, Anuradhaa

AU - Champsi, Asgher

AU - Wang, Xiaoxia

AU - Myles, Puja

AU - McGreavy, Paul

AU - Bunting, Karina V

AU - Shukla, David

AU - Nirantharakumar, Krishnarajah

AU - Kotecha, Dipak

N1 - Acknowledgements The study staff are funded by the National Institute for Health and Care Research (NIHR Birmingham Biomedical Research Centre; NIHR203326; D.K.), MRC Health Data Research UK (HDRUK/CFC/01), NHS Data for R&D Subnational Secure Data Environment program (West Midlands; D.K.) and the British Heart Foundation Accelerator Award to the University of Birmingham (AA/18/2/34218). The DaRe2THINK trial is funded by the National Institute for Health and Care Research (NIHR130280; D.K. and D.S.), with medications funded by the NHS (UK Department of Health and Social Care). The opinions expressed in this paper are those of the authors and do not represent any of the listed organizations; none of the organizations had any role in design or conduct of the study (including collection, analysis and interpretation of the data) or any involvement in preparation, review or approval of the manuscript. The funders of the study had no role in study design, data collection, data analysis, data interpretation or writing of the report. © 2024. The Author(s).

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N2 - 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.

AB - 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.

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

Abstract

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Preventing stroke, premature death and cognitive decline in a broader community of patients with atrial fibrillation using healthcare data for pragmatic research (DaRe2THINK)

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