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Meta-Analysis
. 2025 May 6;333(17):1508-1519.
doi: 10.1001/jama.2025.2033.

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

Writing Committee for the PERSIST Collaborators; Faizan Khan  1 , Vignan Yogendrakumar  2   3 , Ronda Lun  1 , Aravind Ganesh  1 , Philip A Barber  1 , Vasileios-Arsenios Lioutas  4 , Naja Emborg Vinding  5 , Ale Algra  6 , Christian Weimar  7 , Joachim Ögren  8 , Jodi D Edwards  9 , Richard H Swartz  10 , Angel Ois  11 , Eva Giralt-Steinhauer  11 , Andrej Netland Khanevski  12 , Xinyi Leng  13 , Xuan Tian  13 , Thomas W Leung  13 , Hong-Kyun Park  14 , Hee-Joon Bae  15 , Masahiro Kamouchi  16 , Tetsuro Ago  16 , Esmee Verburgt  17 , Jamie Verhoeven  17 , Frank-Erik de Leeuw  17 , Bernhard P Berghout  18 , M Kamran Ikram  18 , Karel Kostev  19 , William Whiteley  20   21 , Toshiyuki Uehara  22 , Kazuo Minematsu  23 , Fredrik Ildstad  24 , Simon Fandler-Höfler  25 , Karoliina Aarnio  26 , Bettina von Sarnowski  27 , Matteo Foschi  28 , Jing Jing  29 , Minyoul Baik  30 , Young Dae Kim  31 , Michele Domenico Spampinato  32 , Yasuhiro Hasegawa  33 , Kanjana Perera  21 , Francisco Purroy  34 , Dipankar Dutta  35 , Xiaoli Yang  36 , Julian Lippert  36 , Laura Myers  37 , Dawn M Bravata  37 , Monica Santos  38 , Sarah Coveney  39 , Carlos Garcia-Esperon  40 , Christopher R Levi  40 , Diane L Lorenzetti  41 , Shabnam Vatanpour  1 , Yongjun Wang  29 , Gregory W Albers  42 , Philippa Lavallee  43 , Pierre Amarenco  21   43 , Shelagh B Coutts  1 , Michael D Hill  1   44
Affiliations
Meta-Analysis

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

Writing Committee for the PERSIST Collaborators et al. JAMA. .

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 Unpublished aggregate-level data on number of events and person-years during discrete follow-up intervals were obtained directly from the authors of the included studies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.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Khan reported employment for Bristol Myers Squibb that commenced after completion of the study and writing of the manuscript. Dr Ganesh reported stock options from SnapDx Inc and Let’s Get Proof (previously Collavidence Inc) and personal fees from Alexion, Biogen, Eisai, and Servier Canada outside the submitted work. Dr Swartz reported grants from the Canadian Institutes of Health Research during the conduct of the study and personal fees from Hoffmann La Roche (advisory board) and stock ownership from FollowMD Inc outside the submitted work. Dr Bae reported grants from Otsuka Korea, Korean Drug Co Ltd, Samjin Pharmaceutical, Dong-A ST, Takeda Pharmaceuticals Korea Co Ltd, BMS Korea, Bayer Korea, Chong Kun Dang Pharmaceutical Corp, Amgen Korea, and JW Pharmaceutical and personal fees from Bayer, Hanmi Pharmaceutical Co Ltd, Otsuka Korea, SK Chemicals, Amgen Korea, and Daiichi Sankyo outside the submitted work. Dr de Leeuw reported being an unpaid associate editor of the International Journal of Stroke. Dr Fandler-Höfler reported personal fees from AstraZeneca outside the submitted work. Dr Aarnio reported grants from Maire Taponen Foundation during the conduct of the study. Dr Perera reported grants from the Canadian Institutes of Health Research and Bayer AG outside the submitted work. Dr Myers reported grants from Department of Veterans Affairs during the conduct of the study. Dr Garcia-Esperon reported speaker honoraria from AstraZeneca and American Academy of Neurology and travel funding from Boehringer Ingelheim and Bayer outside the submitted work. Dr Amarenco reported grants from AstraZeneca (THETIS trial), Pfizer (TST trial), and French government (RIISC-THETIS, TST, TST-3C-SVD, SPICAF trials) and personal fees from Neuraltide, Novartis, Sanofi, and Viatris outside the submitted work. Dr Hill reported grants from NoNO Inc (to the University of Calgary for the ESCAPE-NEXT trial), Medtronic LLC (to the University of Calgary for the ESCAPE-MeVO trial), and Boehringer Ingelheim (to the University of Calgary for the ACT-GLOBAL trial) outside the submitted work; as well as consulting roles to Basking Biosciences for the RAISE trial and Diamedica for the REMEDY2 trial and as a data and safety monitoring committee member role for the LAAOS-4 trial. No other disclosures were reported.

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