Long-Term Risk of Stroke After Transient Ischemic Attack or Minor Stroke: A Systematic Review and Meta-Analysis

Faizan Khan; Vignan Yogendrakumar; Ronda Lun; Aravind Ganesh; Philip A Barber; Vasileios-Arsenios Lioutas; Naja Emborg Vinding; Ale Algra; Christian Weimar; Joachim Ögren; Jodi D Edwards; Richard H Swartz; Angel Ois; Eva Giralt-Steinhauer; Andrej Netland Khanevski; Xinyi Leng; Xuan Tian; Thomas W Leung; Hong-Kyun Park; Hee-Joon Bae; Masahiro Kamouchi; Tetsuro Ago; Esmee Verburgt; Jamie Verhoeven; Frank-Erik de Leeuw; Bernhard P Berghout; M Kamran Ikram; Karel Kostev; William Whiteley; Toshiyuki Uehara; Kazuo Minematsu; Fredrik Ildstad; Simon Fandler-Höfler; Karoliina Aarnio; Bettina von Sarnowski; Matteo Foschi; Jing Jing; Minyoul Baik; Young Dae Kim; Michele Domenico Spampinato; Yasuhiro Hasegawa; Kanjana Perera; Francisco Purroy; Dipankar Dutta; Xiaoli Yang; Julian Lippert; Laura Myers; Dawn M Bravata; Monica Santos; Sarah Coveney

doi:10.1001/jama.2025.2033

Long-Term Risk of Stroke After Transient Ischemic Attack or Minor Stroke: A Systematic Review and Meta-Analysis

Faizan Khan^*, Vignan Yogendrakumar, Ronda Lun, Aravind Ganesh, Philip A Barber, Vasileios-Arsenios Lioutas, Naja Emborg Vinding, Ale Algra, Christian Weimar, Joachim Ögren, Jodi D Edwards, Richard H Swartz, Angel Ois, Eva Giralt-Steinhauer, Andrej Netland Khanevski, Xinyi Leng, Xuan Tian, Thomas W Leung, Hong-Kyun Park, Hee-Joon BaeMasahiro Kamouchi, Tetsuro Ago, Esmee Verburgt, Jamie Verhoeven, Frank-Erik de Leeuw, Bernhard P Berghout, M Kamran Ikram, Karel Kostev, William Whiteley, Toshiyuki Uehara, Kazuo Minematsu, Fredrik Ildstad, Simon Fandler-Höfler, Karoliina Aarnio, Bettina von Sarnowski, Matteo Foschi, Jing Jing, Minyoul Baik, Young Dae Kim, Michele Domenico Spampinato, Yasuhiro Hasegawa, Kanjana Perera, Francisco Purroy, Dipankar Dutta, Xiaoli Yang, Julian Lippert, Laura Myers, Dawn M Bravata, Monica Santos, Sarah Coveney,

^*Corresponding author for this work

Julius Center, dept. Epidemiology & Health Economics

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

Abstract

IMPORTANCE: After a transient ischemic attack (TIA) or minor stroke, the long-term risk of stroke is not well-known.

OBJECTIVE: To determine the annual incidence rates and cumulative incidences of stroke up to 10 years after TIA or minor stroke.

DATA SOURCES: MEDLINE, Embase, and Web of Science were searched from inception through June 26, 2024.

STUDY SELECTION: Prospective or retrospective cohort studies reporting stroke risk during a minimum follow-up of 1 year in patients with TIA or minor stroke.

DATA EXTRACTION AND SYNTHESIS: Two reviewers independently performed data extraction and assessed study quality. Unpublished aggregate-level data on number of events and person-years during discrete follow-up intervals were obtained directly from the authors of the included studies to calculate incidence rates in individual studies. Data across studies were pooled using random-effects meta-analysis.

MAIN OUTCOMES AND MEASURES: The primary outcome was any stroke. Study-level characteristics were investigated as potential sources of variability in stroke rates across studies.

RESULTS: The analysis involved 171 068 patients (median age, 69 years [IQR, 65-71]; median proportion of male patients, 57% [IQR, 52%-60%]) from 38 included studies. The pooled rate of stroke per 100 person-years was 5.94 events (95% CI, 5.18-6.76; 38 studies; I2 = 97%) in the first year, 1.80 events (95% CI, 1.58-2.04; 25 studies; I2 = 90%) annually in the second through fifth years, and 1.72 events (95% CI, 1.31-2.18; 12 studies; I2 = 84%) annually in the sixth through tenth years. The 5- and 10-year cumulative incidence of stroke was 12.5% (95% CI, 11.0%-14.1%) and 19.8% (95% CI, 16.7%-23.1%), respectively. Stroke rates were higher in studies conducted in North America (rate ratio [RR], 1.43 [95% CI, 1.36-1.50]) and Asia (RR, 1.62 [95% CI, 1.52-1.73]), compared with Europe, in cohorts recruited in or after 2007 (RR, 1.42 [95% CI, 1.23-1.64]), and in studies that used active vs passive outcome ascertainment methods (RR, 1.11 [95% CI, 1.07-1.17]). Studies focusing solely on patients with TIA (RR, 0.68 [95% CI, 0.65-0.71) or first-ever index events (RR, 0.45 [95% CI, 0.42-0.49]) had lower stroke rates than studies with an unselected patient population.

CONCLUSIONS AND RELEVANCE: Patients who have had a TIA or minor stroke are at a persistently high risk of subsequent stroke. Findings from this study underscore the need for improving long-term stroke prevention measures in this patient group.

Original language	English
Pages (from-to)	1508-1519
Number of pages	12
Journal	JAMA
Volume	333
Issue number	17
Early online date	26 Mar 2025
DOIs	https://doi.org/10.1001/jama.2025.2033
Publication status	Published - 2025

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10.1001/jama.2025.2033

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Khan, F., Yogendrakumar, V., Lun, R., Ganesh, A., Barber, P. A., Lioutas, V.-A., Vinding, N. E., Algra, A., Weimar, C., Ögren, J., Edwards, J. D., Swartz, R. H., Ois, A., Giralt-Steinhauer, E., Khanevski, A. N., Leng, X., Tian, X., Leung, T. W., Park, H.-K. (2025). Long-Term Risk of Stroke After Transient Ischemic Attack or Minor Stroke: A Systematic Review and Meta-Analysis. JAMA, 333(17), 1508-1519. https://doi.org/10.1001/jama.2025.2033

@article{e6af41101e4b40ae9445fc289e92885a,

title = "Long-Term Risk of Stroke After Transient Ischemic Attack or Minor Stroke: A Systematic Review and Meta-Analysis",

abstract = "IMPORTANCE: After a transient ischemic attack (TIA) or minor stroke, the long-term risk of stroke is not well-known.OBJECTIVE: To determine the annual incidence rates and cumulative incidences of stroke up to 10 years after TIA or minor stroke.DATA SOURCES: MEDLINE, Embase, and Web of Science were searched from inception through June 26, 2024.STUDY SELECTION: Prospective or retrospective cohort studies reporting stroke risk during a minimum follow-up of 1 year in patients with TIA or minor stroke.DATA EXTRACTION AND SYNTHESIS: Two reviewers independently performed data extraction and assessed study quality. Unpublished aggregate-level data on number of events and person-years during discrete follow-up intervals were obtained directly from the authors of the included studies to calculate incidence rates in individual studies. Data across studies were pooled using random-effects meta-analysis.MAIN OUTCOMES AND MEASURES: The primary outcome was any stroke. Study-level characteristics were investigated as potential sources of variability in stroke rates across studies.RESULTS: The analysis involved 171 068 patients (median age, 69 years [IQR, 65-71]; median proportion of male patients, 57% [IQR, 52%-60%]) from 38 included studies. The pooled rate of stroke per 100 person-years was 5.94 events (95% CI, 5.18-6.76; 38 studies; I2 = 97%) in the first year, 1.80 events (95% CI, 1.58-2.04; 25 studies; I2 = 90%) annually in the second through fifth years, and 1.72 events (95% CI, 1.31-2.18; 12 studies; I2 = 84%) annually in the sixth through tenth years. The 5- and 10-year cumulative incidence of stroke was 12.5% (95% CI, 11.0%-14.1%) and 19.8% (95% CI, 16.7%-23.1%), respectively. Stroke rates were higher in studies conducted in North America (rate ratio [RR], 1.43 [95% CI, 1.36-1.50]) and Asia (RR, 1.62 [95% CI, 1.52-1.73]), compared with Europe, in cohorts recruited in or after 2007 (RR, 1.42 [95% CI, 1.23-1.64]), and in studies that used active vs passive outcome ascertainment methods (RR, 1.11 [95% CI, 1.07-1.17]). Studies focusing solely on patients with TIA (RR, 0.68 [95% CI, 0.65-0.71) or first-ever index events (RR, 0.45 [95% CI, 0.42-0.49]) had lower stroke rates than studies with an unselected patient population.CONCLUSIONS AND RELEVANCE: Patients who have had a TIA or minor stroke are at a persistently high risk of subsequent stroke. Findings from this study underscore the need for improving long-term stroke prevention measures in this patient group.",

author = "Faizan Khan and Vignan Yogendrakumar and Ronda Lun and Aravind Ganesh and Barber, {Philip A} and Vasileios-Arsenios Lioutas and Vinding, {Naja Emborg} and Ale Algra and Christian Weimar and Joachim {\"O}gren and Edwards, {Jodi D} and Swartz, {Richard H} and Angel Ois and Eva Giralt-Steinhauer and Khanevski, {Andrej Netland} and Xinyi Leng and Xuan Tian and Leung, {Thomas W} and Hong-Kyun Park and Hee-Joon Bae and Masahiro Kamouchi and Tetsuro Ago and Esmee Verburgt and Jamie Verhoeven and {de Leeuw}, Frank-Erik and Berghout, {Bernhard P} and Ikram, {M Kamran} and Karel Kostev and William Whiteley and Toshiyuki Uehara and Kazuo Minematsu and Fredrik Ildstad and Simon Fandler-H{\"o}fler and Karoliina Aarnio and {von Sarnowski}, Bettina and Matteo Foschi and Jing Jing and Minyoul Baik and Kim, {Young Dae} and Spampinato, {Michele Domenico} and Yasuhiro Hasegawa and Kanjana Perera and Francisco Purroy and Dipankar Dutta and Xiaoli Yang and Julian Lippert and Laura Myers and Bravata, {Dawn M} and Monica Santos and Sarah Coveney",

year = "2025",

doi = "10.1001/jama.2025.2033",

language = "English",

volume = "333",

pages = "1508--1519",

number = "17",

}

Khan, F, Yogendrakumar, V, Lun, R, Ganesh, A, Barber, PA, Lioutas, V-A, Vinding, NE, Algra, A, Weimar, C, Ögren, J, Edwards, JD, Swartz, RH, Ois, A, Giralt-Steinhauer, E, Khanevski, AN, Leng, X, Tian, X, Leung, TW, Park, H-K, Bae, H-J, Kamouchi, M, Ago, T, Verburgt, E, Verhoeven, J, de Leeuw, F-E, Berghout, BP, Ikram, MK, Kostev, K, Whiteley, W, Uehara, T, Minematsu, K, Ildstad, F, Fandler-Höfler, S, Aarnio, K, von Sarnowski, B, Foschi, M, Jing, J, Baik, M, Kim, YD, Spampinato, MD, Hasegawa, Y, Perera, K, Purroy, F, Dutta, D, Yang, X, Lippert, J, Myers, L, Bravata, DM, Santos, M, Coveney, S 2025, 'Long-Term Risk of Stroke After Transient Ischemic Attack or Minor Stroke: A Systematic Review and Meta-Analysis', JAMA, vol. 333, no. 17, pp. 1508-1519. https://doi.org/10.1001/jama.2025.2033

TY - JOUR

T1 - Long-Term Risk of Stroke After Transient Ischemic Attack or Minor Stroke

T2 - A Systematic Review and Meta-Analysis

AU - Khan, Faizan

AU - Yogendrakumar, Vignan

AU - Lun, Ronda

AU - Ganesh, Aravind

AU - Barber, Philip A

AU - Lioutas, Vasileios-Arsenios

AU - Vinding, Naja Emborg

AU - Algra, Ale

AU - Weimar, Christian

AU - Ögren, Joachim

AU - Edwards, Jodi D

AU - Swartz, Richard H

AU - Ois, Angel

AU - Giralt-Steinhauer, Eva

AU - Khanevski, Andrej Netland

AU - Leng, Xinyi

AU - Tian, Xuan

AU - Leung, Thomas W

AU - Park, Hong-Kyun

AU - Bae, Hee-Joon

AU - Kamouchi, Masahiro

AU - Ago, Tetsuro

AU - Verburgt, Esmee

AU - Verhoeven, Jamie

AU - de Leeuw, Frank-Erik

AU - Berghout, Bernhard P

AU - Ikram, M Kamran

AU - Kostev, Karel

AU - Whiteley, William

AU - Uehara, Toshiyuki

AU - Minematsu, Kazuo

AU - Ildstad, Fredrik

AU - Fandler-Höfler, Simon

AU - Aarnio, Karoliina

AU - von Sarnowski, Bettina

AU - Foschi, Matteo

AU - Jing, Jing

AU - Baik, Minyoul

AU - Kim, Young Dae

AU - Spampinato, Michele Domenico

AU - Hasegawa, Yasuhiro

AU - Perera, Kanjana

AU - Purroy, Francisco

AU - Dutta, Dipankar

AU - Yang, Xiaoli

AU - Lippert, Julian

AU - Myers, Laura

AU - Bravata, Dawn M

AU - Santos, Monica

AU - Coveney, Sarah

PY - 2025

Y1 - 2025

N2 - IMPORTANCE: After a transient ischemic attack (TIA) or minor stroke, the long-term risk of stroke is not well-known.OBJECTIVE: To determine the annual incidence rates and cumulative incidences of stroke up to 10 years after TIA or minor stroke.DATA SOURCES: MEDLINE, Embase, and Web of Science were searched from inception through June 26, 2024.STUDY SELECTION: Prospective or retrospective cohort studies reporting stroke risk during a minimum follow-up of 1 year in patients with TIA or minor stroke.DATA EXTRACTION AND SYNTHESIS: Two reviewers independently performed data extraction and assessed study quality. Unpublished aggregate-level data on number of events and person-years during discrete follow-up intervals were obtained directly from the authors of the included studies to calculate incidence rates in individual studies. Data across studies were pooled using random-effects meta-analysis.MAIN OUTCOMES AND MEASURES: The primary outcome was any stroke. Study-level characteristics were investigated as potential sources of variability in stroke rates across studies.RESULTS: The analysis involved 171 068 patients (median age, 69 years [IQR, 65-71]; median proportion of male patients, 57% [IQR, 52%-60%]) from 38 included studies. The pooled rate of stroke per 100 person-years was 5.94 events (95% CI, 5.18-6.76; 38 studies; I2 = 97%) in the first year, 1.80 events (95% CI, 1.58-2.04; 25 studies; I2 = 90%) annually in the second through fifth years, and 1.72 events (95% CI, 1.31-2.18; 12 studies; I2 = 84%) annually in the sixth through tenth years. The 5- and 10-year cumulative incidence of stroke was 12.5% (95% CI, 11.0%-14.1%) and 19.8% (95% CI, 16.7%-23.1%), respectively. Stroke rates were higher in studies conducted in North America (rate ratio [RR], 1.43 [95% CI, 1.36-1.50]) and Asia (RR, 1.62 [95% CI, 1.52-1.73]), compared with Europe, in cohorts recruited in or after 2007 (RR, 1.42 [95% CI, 1.23-1.64]), and in studies that used active vs passive outcome ascertainment methods (RR, 1.11 [95% CI, 1.07-1.17]). Studies focusing solely on patients with TIA (RR, 0.68 [95% CI, 0.65-0.71) or first-ever index events (RR, 0.45 [95% CI, 0.42-0.49]) had lower stroke rates than studies with an unselected patient population.CONCLUSIONS AND RELEVANCE: Patients who have had a TIA or minor stroke are at a persistently high risk of subsequent stroke. Findings from this study underscore the need for improving long-term stroke prevention measures in this patient group.

AB - IMPORTANCE: After a transient ischemic attack (TIA) or minor stroke, the long-term risk of stroke is not well-known.OBJECTIVE: To determine the annual incidence rates and cumulative incidences of stroke up to 10 years after TIA or minor stroke.DATA SOURCES: MEDLINE, Embase, and Web of Science were searched from inception through June 26, 2024.STUDY SELECTION: Prospective or retrospective cohort studies reporting stroke risk during a minimum follow-up of 1 year in patients with TIA or minor stroke.DATA EXTRACTION AND SYNTHESIS: Two reviewers independently performed data extraction and assessed study quality. Unpublished aggregate-level data on number of events and person-years during discrete follow-up intervals were obtained directly from the authors of the included studies to calculate incidence rates in individual studies. Data across studies were pooled using random-effects meta-analysis.MAIN OUTCOMES AND MEASURES: The primary outcome was any stroke. Study-level characteristics were investigated as potential sources of variability in stroke rates across studies.RESULTS: The analysis involved 171 068 patients (median age, 69 years [IQR, 65-71]; median proportion of male patients, 57% [IQR, 52%-60%]) from 38 included studies. The pooled rate of stroke per 100 person-years was 5.94 events (95% CI, 5.18-6.76; 38 studies; I2 = 97%) in the first year, 1.80 events (95% CI, 1.58-2.04; 25 studies; I2 = 90%) annually in the second through fifth years, and 1.72 events (95% CI, 1.31-2.18; 12 studies; I2 = 84%) annually in the sixth through tenth years. The 5- and 10-year cumulative incidence of stroke was 12.5% (95% CI, 11.0%-14.1%) and 19.8% (95% CI, 16.7%-23.1%), respectively. Stroke rates were higher in studies conducted in North America (rate ratio [RR], 1.43 [95% CI, 1.36-1.50]) and Asia (RR, 1.62 [95% CI, 1.52-1.73]), compared with Europe, in cohorts recruited in or after 2007 (RR, 1.42 [95% CI, 1.23-1.64]), and in studies that used active vs passive outcome ascertainment methods (RR, 1.11 [95% CI, 1.07-1.17]). Studies focusing solely on patients with TIA (RR, 0.68 [95% CI, 0.65-0.71) or first-ever index events (RR, 0.45 [95% CI, 0.42-0.49]) had lower stroke rates than studies with an unselected patient population.CONCLUSIONS AND RELEVANCE: Patients who have had a TIA or minor stroke are at a persistently high risk of subsequent stroke. Findings from this study underscore the need for improving long-term stroke prevention measures in this patient group.

U2 - 10.1001/jama.2025.2033

DO - 10.1001/jama.2025.2033

M3 - Article

C2 - 40136306

SN - 0098-7484

VL - 333

SP - 1508

EP - 1519

JO - JAMA

JF - JAMA

IS - 17

ER -

Long-Term Risk of Stroke After Transient Ischemic Attack or Minor Stroke: A Systematic Review and Meta-Analysis

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