Validation and comparison of imaging-based scores for prediction of early stroke risk after transient ischaemic attack

a pooled analysis of individual-patient data from cohort studies

Peter J. Kelly, Gregory W. Albers, Anastasios Chatzikonstantinou, Gian Marco De Marchis, Julia Ferrari, Paul George, Mira Katan, Michael Knoflach, Jong S. Kim, Linxin Li, Eun Jae Lee, Jean Marc Olivot, Francisco Purroy, Nicolas Raposo, Peter M. Rothwell, Vijay K. Sharma, Bo Song, Georgios Tsivgoulis, Cathal Walsh, Yuming Xu & 1 others Aine Merwick

Research output: Contribution to journalArticle

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Abstract

Background Identification of patients at highest risk of early stroke after transient ischaemic attack has been improved with imaging based scores. We aimed to compare the validity and prognostic utility of imaging-based stroke risk scores in patients after transient ischaemic attack. Methods We did a pooled analysis of published and unpublished individual-patient data from 16 cohort studies of transient ischaemic attack done in Asia, Europe, and the USA, with early brain and vascular imaging and follow up. All patients were assessed by stroke specialists in hospital settings as inpatients, in emergency departments, or in transient ischaemic attack clinics. Inclusion criteria were stroke-specialist confirmed transient ischaemic attack, age of 18 years or older, and MRI done within 7 days of index transient ischaemic attack and before stroke recurrence. Multivariable logistic regression was done to analyse the predictive utility of abnormal diffusion-weighted MRI, carotid stenosis, and transient ischaemic attack within 1 week of index transient ischaemic attack (dual transient ischaemic attack) after adjusting for ABCD2 score. We compared the prognostic utility of the ABCD2, ABCD2-I, and ABCD3-I scores using discrimination, calibration, and risk reclassification. Findings In 2176 patients from 16 cohort studies done between 2005 and 2015, after adjusting for ABCD2 score, positive diffusion-weighted imaging (odds ratio [OR] 3·8, 95% CI 2·1–7·0), dual transient ischaemic attack (OR 3·3, 95% CI 1·8–5·8), and ipsilateral carotid stenosis (OR 4·7, 95% CI 2·6–8·6) were associated with 7 day stroke after index transient ischaemic attack (p<0·001 for all). 7 day stroke risk increased with increasing ABCD2-I and ABCD3-I scores (both p<0·001). Discrimination to identify early stroke risk was improved for ABCD2-I versus ABCD2 (2 day c statistic 0·74 vs 0·64; p=0·006). However, discrimination was further improved by ABCD3-I compared with ABCD2 (2 day c statistic 0·84 vs 0·64; p<0·001) and ABCD2-I (c statistic 0·84 vs 0·74; p<0·001). Early stroke risk reclassification was improved by ABCD3-I compared with ABCD2-I score (clinical net reclassification improvement 33% at 2 days). Interpretation Although ABCD2-I and ABCD3-I showed validity, the ABCD3-I score reliably identified highest-risk patients at highest risk of a stroke after transient ischaemic attack with improved risk prediction compared with ABCD2-I. Transient ischaemic attack management guided by ABCD3-I with immediate stroke-specialist assessment, urgent MRI, and vascular imaging should now be considered, with monitoring of safety and cost-effectiveness. Funding Health Research Board of Ireland, Irish Heart Foundation, Irish Health Service Executive, Irish National Lottery, National Medical Research Council of Singapore, Swiss National Science Foundation, Bangerter-Rhyner Foundation, Swiss National Science Foundation, Swisslife Jubiläumsstiftung for Medical Research, Swiss Neurological Society, Fondazione Dr Ettore Balli (Switzerland), Clinical Trial Unit of University of Bern, South Korea's Ministry for Health, Welfare, and Family Affairs, UK Wellcome Trust, Wolfson Foundation, UK Stroke Association, British Heart Foundation, Dunhill Medical Trust, National Institute of Health Research (NIHR), Medical Research Council, and the NIHR Oxford Biomedical Research Centre.

Original languageEnglish (US)
Pages (from-to)1238-1247
Number of pages10
JournalThe Lancet Neurology
Volume15
Issue number12
DOIs
StatePublished - Nov 1 2016

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Transient Ischemic Attack
Cohort Studies
Stroke
Biomedical Research
Carotid Stenosis
Odds Ratio
National Institutes of Health (U.S.)
Blood Vessels
Research
Republic of Korea
Diffusion Magnetic Resonance Imaging
Family Health
Singapore
Switzerland
Ireland
Neuroimaging
Calibration
Health Services
Cost-Benefit Analysis
Hospital Emergency Service

All Science Journal Classification (ASJC) codes

  • Clinical Neurology

Cite this

Validation and comparison of imaging-based scores for prediction of early stroke risk after transient ischaemic attack : a pooled analysis of individual-patient data from cohort studies. / Kelly, Peter J.; Albers, Gregory W.; Chatzikonstantinou, Anastasios; De Marchis, Gian Marco; Ferrari, Julia; George, Paul; Katan, Mira; Knoflach, Michael; Kim, Jong S.; Li, Linxin; Lee, Eun Jae; Olivot, Jean Marc; Purroy, Francisco; Raposo, Nicolas; Rothwell, Peter M.; Sharma, Vijay K.; Song, Bo; Tsivgoulis, Georgios; Walsh, Cathal; Xu, Yuming; Merwick, Aine.

In: The Lancet Neurology, Vol. 15, No. 12, 01.11.2016, p. 1238-1247.

Research output: Contribution to journalArticle

Kelly, PJ, Albers, GW, Chatzikonstantinou, A, De Marchis, GM, Ferrari, J, George, P, Katan, M, Knoflach, M, Kim, JS, Li, L, Lee, EJ, Olivot, JM, Purroy, F, Raposo, N, Rothwell, PM, Sharma, VK, Song, B, Tsivgoulis, G, Walsh, C, Xu, Y & Merwick, A 2016, 'Validation and comparison of imaging-based scores for prediction of early stroke risk after transient ischaemic attack: a pooled analysis of individual-patient data from cohort studies', The Lancet Neurology, vol. 15, no. 12, pp. 1238-1247. https://doi.org/10.1016/S1474-4422(16)30236-8
Kelly, Peter J. ; Albers, Gregory W. ; Chatzikonstantinou, Anastasios ; De Marchis, Gian Marco ; Ferrari, Julia ; George, Paul ; Katan, Mira ; Knoflach, Michael ; Kim, Jong S. ; Li, Linxin ; Lee, Eun Jae ; Olivot, Jean Marc ; Purroy, Francisco ; Raposo, Nicolas ; Rothwell, Peter M. ; Sharma, Vijay K. ; Song, Bo ; Tsivgoulis, Georgios ; Walsh, Cathal ; Xu, Yuming ; Merwick, Aine. / Validation and comparison of imaging-based scores for prediction of early stroke risk after transient ischaemic attack : a pooled analysis of individual-patient data from cohort studies. In: The Lancet Neurology. 2016 ; Vol. 15, No. 12. pp. 1238-1247.
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abstract = "Background Identification of patients at highest risk of early stroke after transient ischaemic attack has been improved with imaging based scores. We aimed to compare the validity and prognostic utility of imaging-based stroke risk scores in patients after transient ischaemic attack. Methods We did a pooled analysis of published and unpublished individual-patient data from 16 cohort studies of transient ischaemic attack done in Asia, Europe, and the USA, with early brain and vascular imaging and follow up. All patients were assessed by stroke specialists in hospital settings as inpatients, in emergency departments, or in transient ischaemic attack clinics. Inclusion criteria were stroke-specialist confirmed transient ischaemic attack, age of 18 years or older, and MRI done within 7 days of index transient ischaemic attack and before stroke recurrence. Multivariable logistic regression was done to analyse the predictive utility of abnormal diffusion-weighted MRI, carotid stenosis, and transient ischaemic attack within 1 week of index transient ischaemic attack (dual transient ischaemic attack) after adjusting for ABCD2 score. We compared the prognostic utility of the ABCD2, ABCD2-I, and ABCD3-I scores using discrimination, calibration, and risk reclassification. Findings In 2176 patients from 16 cohort studies done between 2005 and 2015, after adjusting for ABCD2 score, positive diffusion-weighted imaging (odds ratio [OR] 3·8, 95{\%} CI 2·1–7·0), dual transient ischaemic attack (OR 3·3, 95{\%} CI 1·8–5·8), and ipsilateral carotid stenosis (OR 4·7, 95{\%} CI 2·6–8·6) were associated with 7 day stroke after index transient ischaemic attack (p<0·001 for all). 7 day stroke risk increased with increasing ABCD2-I and ABCD3-I scores (both p<0·001). Discrimination to identify early stroke risk was improved for ABCD2-I versus ABCD2 (2 day c statistic 0·74 vs 0·64; p=0·006). However, discrimination was further improved by ABCD3-I compared with ABCD2 (2 day c statistic 0·84 vs 0·64; p<0·001) and ABCD2-I (c statistic 0·84 vs 0·74; p<0·001). Early stroke risk reclassification was improved by ABCD3-I compared with ABCD2-I score (clinical net reclassification improvement 33{\%} at 2 days). Interpretation Although ABCD2-I and ABCD3-I showed validity, the ABCD3-I score reliably identified highest-risk patients at highest risk of a stroke after transient ischaemic attack with improved risk prediction compared with ABCD2-I. Transient ischaemic attack management guided by ABCD3-I with immediate stroke-specialist assessment, urgent MRI, and vascular imaging should now be considered, with monitoring of safety and cost-effectiveness. Funding Health Research Board of Ireland, Irish Heart Foundation, Irish Health Service Executive, Irish National Lottery, National Medical Research Council of Singapore, Swiss National Science Foundation, Bangerter-Rhyner Foundation, Swiss National Science Foundation, Swisslife Jubil{\"a}umsstiftung for Medical Research, Swiss Neurological Society, Fondazione Dr Ettore Balli (Switzerland), Clinical Trial Unit of University of Bern, South Korea's Ministry for Health, Welfare, and Family Affairs, UK Wellcome Trust, Wolfson Foundation, UK Stroke Association, British Heart Foundation, Dunhill Medical Trust, National Institute of Health Research (NIHR), Medical Research Council, and the NIHR Oxford Biomedical Research Centre.",
author = "Kelly, {Peter J.} and Albers, {Gregory W.} and Anastasios Chatzikonstantinou and {De Marchis}, {Gian Marco} and Julia Ferrari and Paul George and Mira Katan and Michael Knoflach and Kim, {Jong S.} and Linxin Li and Lee, {Eun Jae} and Olivot, {Jean Marc} and Francisco Purroy and Nicolas Raposo and Rothwell, {Peter M.} and Sharma, {Vijay K.} and Bo Song and Georgios Tsivgoulis and Cathal Walsh and Yuming Xu and Aine Merwick",
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TY - JOUR

T1 - Validation and comparison of imaging-based scores for prediction of early stroke risk after transient ischaemic attack

T2 - a pooled analysis of individual-patient data from cohort studies

AU - Kelly, Peter J.

AU - Albers, Gregory W.

AU - Chatzikonstantinou, Anastasios

AU - De Marchis, Gian Marco

AU - Ferrari, Julia

AU - George, Paul

AU - Katan, Mira

AU - Knoflach, Michael

AU - Kim, Jong S.

AU - Li, Linxin

AU - Lee, Eun Jae

AU - Olivot, Jean Marc

AU - Purroy, Francisco

AU - Raposo, Nicolas

AU - Rothwell, Peter M.

AU - Sharma, Vijay K.

AU - Song, Bo

AU - Tsivgoulis, Georgios

AU - Walsh, Cathal

AU - Xu, Yuming

AU - Merwick, Aine

PY - 2016/11/1

Y1 - 2016/11/1

N2 - Background Identification of patients at highest risk of early stroke after transient ischaemic attack has been improved with imaging based scores. We aimed to compare the validity and prognostic utility of imaging-based stroke risk scores in patients after transient ischaemic attack. Methods We did a pooled analysis of published and unpublished individual-patient data from 16 cohort studies of transient ischaemic attack done in Asia, Europe, and the USA, with early brain and vascular imaging and follow up. All patients were assessed by stroke specialists in hospital settings as inpatients, in emergency departments, or in transient ischaemic attack clinics. Inclusion criteria were stroke-specialist confirmed transient ischaemic attack, age of 18 years or older, and MRI done within 7 days of index transient ischaemic attack and before stroke recurrence. Multivariable logistic regression was done to analyse the predictive utility of abnormal diffusion-weighted MRI, carotid stenosis, and transient ischaemic attack within 1 week of index transient ischaemic attack (dual transient ischaemic attack) after adjusting for ABCD2 score. We compared the prognostic utility of the ABCD2, ABCD2-I, and ABCD3-I scores using discrimination, calibration, and risk reclassification. Findings In 2176 patients from 16 cohort studies done between 2005 and 2015, after adjusting for ABCD2 score, positive diffusion-weighted imaging (odds ratio [OR] 3·8, 95% CI 2·1–7·0), dual transient ischaemic attack (OR 3·3, 95% CI 1·8–5·8), and ipsilateral carotid stenosis (OR 4·7, 95% CI 2·6–8·6) were associated with 7 day stroke after index transient ischaemic attack (p<0·001 for all). 7 day stroke risk increased with increasing ABCD2-I and ABCD3-I scores (both p<0·001). Discrimination to identify early stroke risk was improved for ABCD2-I versus ABCD2 (2 day c statistic 0·74 vs 0·64; p=0·006). However, discrimination was further improved by ABCD3-I compared with ABCD2 (2 day c statistic 0·84 vs 0·64; p<0·001) and ABCD2-I (c statistic 0·84 vs 0·74; p<0·001). Early stroke risk reclassification was improved by ABCD3-I compared with ABCD2-I score (clinical net reclassification improvement 33% at 2 days). Interpretation Although ABCD2-I and ABCD3-I showed validity, the ABCD3-I score reliably identified highest-risk patients at highest risk of a stroke after transient ischaemic attack with improved risk prediction compared with ABCD2-I. Transient ischaemic attack management guided by ABCD3-I with immediate stroke-specialist assessment, urgent MRI, and vascular imaging should now be considered, with monitoring of safety and cost-effectiveness. Funding Health Research Board of Ireland, Irish Heart Foundation, Irish Health Service Executive, Irish National Lottery, National Medical Research Council of Singapore, Swiss National Science Foundation, Bangerter-Rhyner Foundation, Swiss National Science Foundation, Swisslife Jubiläumsstiftung for Medical Research, Swiss Neurological Society, Fondazione Dr Ettore Balli (Switzerland), Clinical Trial Unit of University of Bern, South Korea's Ministry for Health, Welfare, and Family Affairs, UK Wellcome Trust, Wolfson Foundation, UK Stroke Association, British Heart Foundation, Dunhill Medical Trust, National Institute of Health Research (NIHR), Medical Research Council, and the NIHR Oxford Biomedical Research Centre.

AB - Background Identification of patients at highest risk of early stroke after transient ischaemic attack has been improved with imaging based scores. We aimed to compare the validity and prognostic utility of imaging-based stroke risk scores in patients after transient ischaemic attack. Methods We did a pooled analysis of published and unpublished individual-patient data from 16 cohort studies of transient ischaemic attack done in Asia, Europe, and the USA, with early brain and vascular imaging and follow up. All patients were assessed by stroke specialists in hospital settings as inpatients, in emergency departments, or in transient ischaemic attack clinics. Inclusion criteria were stroke-specialist confirmed transient ischaemic attack, age of 18 years or older, and MRI done within 7 days of index transient ischaemic attack and before stroke recurrence. Multivariable logistic regression was done to analyse the predictive utility of abnormal diffusion-weighted MRI, carotid stenosis, and transient ischaemic attack within 1 week of index transient ischaemic attack (dual transient ischaemic attack) after adjusting for ABCD2 score. We compared the prognostic utility of the ABCD2, ABCD2-I, and ABCD3-I scores using discrimination, calibration, and risk reclassification. Findings In 2176 patients from 16 cohort studies done between 2005 and 2015, after adjusting for ABCD2 score, positive diffusion-weighted imaging (odds ratio [OR] 3·8, 95% CI 2·1–7·0), dual transient ischaemic attack (OR 3·3, 95% CI 1·8–5·8), and ipsilateral carotid stenosis (OR 4·7, 95% CI 2·6–8·6) were associated with 7 day stroke after index transient ischaemic attack (p<0·001 for all). 7 day stroke risk increased with increasing ABCD2-I and ABCD3-I scores (both p<0·001). Discrimination to identify early stroke risk was improved for ABCD2-I versus ABCD2 (2 day c statistic 0·74 vs 0·64; p=0·006). However, discrimination was further improved by ABCD3-I compared with ABCD2 (2 day c statistic 0·84 vs 0·64; p<0·001) and ABCD2-I (c statistic 0·84 vs 0·74; p<0·001). Early stroke risk reclassification was improved by ABCD3-I compared with ABCD2-I score (clinical net reclassification improvement 33% at 2 days). Interpretation Although ABCD2-I and ABCD3-I showed validity, the ABCD3-I score reliably identified highest-risk patients at highest risk of a stroke after transient ischaemic attack with improved risk prediction compared with ABCD2-I. Transient ischaemic attack management guided by ABCD3-I with immediate stroke-specialist assessment, urgent MRI, and vascular imaging should now be considered, with monitoring of safety and cost-effectiveness. Funding Health Research Board of Ireland, Irish Heart Foundation, Irish Health Service Executive, Irish National Lottery, National Medical Research Council of Singapore, Swiss National Science Foundation, Bangerter-Rhyner Foundation, Swiss National Science Foundation, Swisslife Jubiläumsstiftung for Medical Research, Swiss Neurological Society, Fondazione Dr Ettore Balli (Switzerland), Clinical Trial Unit of University of Bern, South Korea's Ministry for Health, Welfare, and Family Affairs, UK Wellcome Trust, Wolfson Foundation, UK Stroke Association, British Heart Foundation, Dunhill Medical Trust, National Institute of Health Research (NIHR), Medical Research Council, and the NIHR Oxford Biomedical Research Centre.

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