Should patients with minor strokes be given thrombolytics?
==========================================================

* Xun Wang
* Yi Dong
* Qiang Dong
* David Wang

## Abstract

Mild stroke symptoms are cited as the reason for not using tissue-type plasminogen activator in 29–43% of time-eligible patients. Previous studies suggested that not all of these patients had a good recovery or even survival to hospital discharge. Since then, stroke guidelines worldwide recommended thrombolysis in minor but disabling strokes.

Dual antiplatelet treatment with aspirin and clopidogrel was more effective than aspirin alone for reducing subsequent events in patients with minor stroke if started within 24 hours of onset in both CHANCE (Clopidogrel in High-Risk Patients with Acute Non-disabling Cerebrovascular Events) and POINT (Platelet-Oriented Inhibition in New TIA and Minor Ischaemic Stroke) trials. Recently, both PRISMS (The Potential of rtPA for Ischemic Strokes With Mild Symptoms) trial and TEMPO-2 (Tenecteplase Versus Standard of Care for Minor Ischemic Stroke With Proven Occlusion) trial showed that treatment with thrombolysis versus antiplatelet did not increase the likelihood of favourable functional outcome at 90 days among patients with minor non-disabling acute ischaemic strokes. Therefore, a narrative review on thrombolysis for patients with minor strokes from published studies may help practicing clinicians.

*   Stroke
*   Thrombolysis
*   Asprin
*   Ischemic Stroke

## Introduction

Mild stroke symptoms are cited as the reason for not using tissue-type plasminogen activator in 29–43% of time-eligible patients.1 2 Previous studies suggested that not all of these patients had a good recovery or even survive to hospital discharge.3–6 A large nationwide study (Get With The Guidelines–Stroke) showed that stroke-related disability in mild stroke is relatively common. They also illustrated the clinical outcomes at discharge were strongly associated with the initial NIHSS(National Institutes of Health Stroke Scale) scores.7 The multinational Safe Implementation of Treatment in Stroke-International Stroke Thrombolysis Registry observational study showed patients with a minor stroke had 71–72% favourable outcome (modified Rankin Scale, mRS 0–1) at 3 months, regardless of the time window of presentation.8 Since then, stroke guidelines worldwide recommended thrombolysis in minor but disabling strokes.9–12

Dual antiplatelet treatment with aspirin and clopidogrel were more effective than aspirin alone for reducing subsequent events in patients with minor stroke if started within 24 hours of onset in both CHANCE (Clopidogrel in High-Risk Patients with Acute Non-disabling Cerebrovascular Events) and POINT (Platelet-Oriented Inhibition in New TIA and Minor Ischaemic Stroke) trials.13 14 Recently, both PRISMS (The Potential of rtPA for Ischemic Strokes With Mild Symptoms) and TEMPO-2 (Tenecteplase Versus Standard of Care for Minor Ischemic Stroke With Proven Occlusion) trials showed that treatment with thrombolysis versus antiplatelet did not increase the likelihood of favourable functional outcome at 90 days among patients with minor nondisabling acute ischaemic strokes.15 16 Therefore, a narrative review on thrombolysis for patients with minor strokes from published studies may help the practicing clinicians (table 1)，

View this table:
[Table 1](http://svn.bmj.com/content/early/2024/12/31/svn-2024-003451/T1)

Table 1 
Different definitions of minor stroke in different studies

## Different criteria of minor stroke

A NIHSS ≤3 or ≤5 were widely used to define a minor stroke, although the consensus is still lacking.17

## Impact of guidelines

Most published guidelines for acute ischaemic stroke suggest thrombolytic therapy to treat patients with a disabling minor ischaemic stroke within 4.5 hours, while most guidelines do not recommend thrombolysis in patients with non-disabling minor strokes. (Table 2).However, disabling stroke has not been defined well. It is also unclear what the best treatment is in patients with acute ischaemic stroke (AIS) low NIHSS but from a large vessel occlusion. Dual antiplatelet therapy could be an option for patients with AIS with an NIHSS<3 and given within 24 hours.

View this table:
[Table 2](http://svn.bmj.com/content/early/2024/12/31/svn-2024-003451/T2)

Table 2 
Comparison of guidelines recommendation on minor stroke and level of evidence

## The ceiling effects and floor effects

A ceiling effect associated with statistics in medical condition refers to the phenomenon in which the majority of the data are close to the upper limit or highest possible score of a test. This means that (almost) all of the test participants achieved the highest (or very near to the highest) score. Recently, PRISMS trial showed 122 patients (78.2%) in the alteplase group versus 128 (81.5%) in the aspirin group achieved a favourable outcome (adjusted risk difference, −1.1%; 95% CI, −9.4% to 7.3%) at 90 days.15 Additionally, ARAMIS (Antiplatelet vs R-tPA for Acute Mild Ischemic Stroke) trial demonstrated that at 90 days, 93.8% of patients (346/369) in the DAPT (dual antiplatelet treatment) group and 91.4% (320/350) in the alteplase group had an excellent functional outcome (risk difference, 2.3% (95% CI, −1.5% to 6.2%)).18 However, TEMPO-2 trial found 50% (226/452) in the control group and 58% (247/432) in the Tenecteplase group recovered to NIHSS 0 at discharge (RR 1.16, 95% CI, 1.01 to 1.31), while the difference became smaller at 90 days for favourable outcome (71% vs 69%, RR 0.97, 95% CI, 0.89 to 1.05).16 From these studies, we have learnt that the rate of 90-day mRS 0–1 in minor stroke was high, which might have already reached the ceiling effect. Since those ceiling effects can impact the quality of studies, an NIHSS of 0 at discharge might be more sensitive.

However, floor effects need to be considered as well. Floor effect is a phenomenon where participants’ scores are generally low and show no differences due to the high difficulty of the experiment. Among these three trials, the numbers of symptomatic intracerebral haemorrhage (sICH) were reported as 5 versus 0, 1 versus 3 and 2 versus 8 in each group, respectively.15 16 18 The haemorrhagic event rate was very low, which made the traditional comparative analytical method very limited.

One post-hoc analysis from the Alteplase Compared with Tenecteplase in Patients With Acute Ischaemic Stroke trial, the primary outcome (mRS score 0–1 at 90 days) among patients with minor stroke occurred in 100 participants (51.8%) in the tenecteplase group and 86 (47.5%) in the alteplase group. There were no significant differences in the rates of sICH (2.9% in tenecteplase vs 3.3% in alteplase group).19 Therefore, the safety and efficacy of thrombolysis in minor stroke from the real-world database might need to be further studied and promising.

## The rate of recurrent stroke and early neurological deterioration

Early neurological deterioration (END) occurs in about 10% of patients after intravenous thrombolysis (IVT) and is related to a poor outcome. In theory, early antiplatelet therapy following IVT could reduce END by preventing re-occlusion and stroke progression.20 However, current guidelines recommend starting antiplatelet treatment at 24 hours after IVT due to concerns of haemorrhagic transformation. Other antithrombotics studied including low molecular-weighted heparin, oral anticoagulation, intravenous tirofiban did not offer a definitive answer on their benefit and risks in preventing recurrent stroke or END.20–22 The ongoing Early Antiplatelet for Minor Stroke Following Thrombolysis trial may provide more information once completed.23

## Brain reperfusion and long-term mental health

In terms of mechanism of action, antiplatelet treatment is for secondary stroke prevention while thrombolysis is to open the occluded artery with brain reperfusion.24 Reperfusion may restore more brain function from strokes and preserve long-term mental health and less cognitive impairment.25 However, data to show the benefit of thrombolysis on post-stroke cognitive impairment is limited.

## Conclusion

Minor stroke is not minor.26 Thrombolysis or not for patients with minor stroke is in hot debate since more data have been published recently. These data suggested that DAPT might be as good as IVT in this group of patients. However, since the definition of a minor stroke may vary, and the long-term outcome such as END and cognition is unclear, selecting DAPT versus IVT remains a choice for the treating physician.

## Ethics statements

### Patient consent for publication

Not applicable.

### Ethics approval

Not applicable.

## Footnotes

*   Collaborators NA.

*   Contributors XW and YD drafted the manuscript, while YD, QD and DW generated the protocol and revised the manuscript.

*   Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

*   Competing interests None declared.

*   Provenance and peer review Not commissioned; internally peer reviewed. Commissioned by the CSA.

[https://creativecommons.org/licenses/by/4.0/](https://creativecommons.org/licenses/by/4.0/)
This is an open access article distributed in accordance with the Creative Commons Attribution 4.0 Unported (CC BY 4.0) license, which permits others to copy, redistribute, remix, transform and build upon this work for any purpose, provided the original work is properly cited, a link to the licence is given, and indication of whether changes were made. See: [https://creativecommons.org/licenses/by/4.0/](https://creativecommons.org/licenses/by/4.0/).

## References

1.  California Acute Stroke Pilot Registry (CASPR) Investigators. Prioritizing interventions to improve rates of thrombolysis for ischemic stroke. Neurol (ECronicon) 2005;64:654–9. [doi:10.1212/01.WNL.0000151850.39648.51](http://dx.doi.org/10.1212/01.WNL.0000151850.39648.51)
    
    

2.  Kleindorfer D, Kissela B, Schneider A, et al. Eligibility for recombinant tissue plasminogen activator in acute ischemic stroke: a population-based study. Stroke 2004;35:e27–9. [doi:10.1161/01.STR.0000109767.11426.17](http://dx.doi.org/10.1161/01.STR.0000109767.11426.17)
    
    [Abstract/FREE Full Text](http://svn.bmj.com/lookup/ijlink/YTozOntzOjQ6InBhdGgiO3M6MTQ6Ii9sb29rdXAvaWpsaW5rIjtzOjU6InF1ZXJ5IjthOjQ6e3M6ODoibGlua1R5cGUiO3M6NDoiQUJTVCI7czoxMToiam91cm5hbENvZGUiO3M6OToic3Ryb2tlYWhhIjtzOjU6InJlc2lkIjtzOjg6IjM1LzIvZTI3IjtzOjQ6ImF0b20iO3M6NDU6Ii9zdm5ibWovZWFybHkvMjAyNC8xMi8zMS9zdm4tMjAyNC0wMDM0NTEuYXRvbSI7fXM6ODoiZnJhZ21lbnQiO3M6MDoiIjt9) 

3.  Smith EE, Abdullah AR, Petkovska I, et al. Poor outcomes in patients who do not receive intravenous tissue plasminogen activator because of mild or improving ischemic stroke. Stroke 2005;36:2497–9. [doi:10.1161/01.STR.0000185798.78817.f3](http://dx.doi.org/10.1161/01.STR.0000185798.78817.f3)
    
    [Abstract/FREE Full Text](http://svn.bmj.com/lookup/ijlink/YTozOntzOjQ6InBhdGgiO3M6MTQ6Ii9sb29rdXAvaWpsaW5rIjtzOjU6InF1ZXJ5IjthOjQ6e3M6ODoibGlua1R5cGUiO3M6NDoiQUJTVCI7czoxMToiam91cm5hbENvZGUiO3M6OToic3Ryb2tlYWhhIjtzOjU6InJlc2lkIjtzOjEwOiIzNi8xMS8yNDk3IjtzOjQ6ImF0b20iO3M6NDU6Ii9zdm5ibWovZWFybHkvMjAyNC8xMi8zMS9zdm4tMjAyNC0wMDM0NTEuYXRvbSI7fXM6ODoiZnJhZ21lbnQiO3M6MDoiIjt9) 

4.  Nedeltchev K, Schwegler B, Haefeli T, et al. Outcome of stroke with mild or rapidly improving symptoms. Stroke 2007;38:2531–5. [doi:10.1161/STROKEAHA.107.482554](http://dx.doi.org/10.1161/STROKEAHA.107.482554)
    
    [Abstract/FREE Full Text](http://svn.bmj.com/lookup/ijlink/YTozOntzOjQ6InBhdGgiO3M6MTQ6Ii9sb29rdXAvaWpsaW5rIjtzOjU6InF1ZXJ5IjthOjQ6e3M6ODoibGlua1R5cGUiO3M6NDoiQUJTVCI7czoxMToiam91cm5hbENvZGUiO3M6OToic3Ryb2tlYWhhIjtzOjU6InJlc2lkIjtzOjk6IjM4LzkvMjUzMSI7czo0OiJhdG9tIjtzOjQ1OiIvc3ZuYm1qL2Vhcmx5LzIwMjQvMTIvMzEvc3ZuLTIwMjQtMDAzNDUxLmF0b20iO31zOjg6ImZyYWdtZW50IjtzOjA6IiI7fQ==) 

5.  Barber PA, Zhang J, Demchuk AM. Why are stroke patients excluded from tpa therapy? An analysis of patient eligibility. Neurol (ECronicon) 2001;56:1015–20. [doi:10.1212/WNL.56.8.1015](http://dx.doi.org/10.1212/WNL.56.8.1015)
    
    

6.  Rajajee V, Kidwell C, Starkman S, et al. Early MRI and outcomes of untreated patients with mild or improving ischemic stroke. Neurol (ECronicon) 2006;67:980–4. [doi:10.1212/01.wnl.0000237520.88777.71](http://dx.doi.org/10.1212/01.wnl.0000237520.88777.71)
    
    

7.  Smith EE, Fonarow GC, Reeves MJ, et al. Outcomes in mild or rapidly improving stroke not treated with intravenous recombinant tissue-type plasminogen activator: findings from get with the guidelines-stroke. Stroke 2011;42:3110–5. [doi:10.1161/STROKEAHA.111.613208](http://dx.doi.org/10.1161/STROKEAHA.111.613208)
    
    [Abstract/FREE Full Text](http://svn.bmj.com/lookup/ijlink/YTozOntzOjQ6InBhdGgiO3M6MTQ6Ii9sb29rdXAvaWpsaW5rIjtzOjU6InF1ZXJ5IjthOjQ6e3M6ODoibGlua1R5cGUiO3M6NDoiQUJTVCI7czoxMToiam91cm5hbENvZGUiO3M6OToic3Ryb2tlYWhhIjtzOjU6InJlc2lkIjtzOjEwOiI0Mi8xMS8zMTEwIjtzOjQ6ImF0b20iO3M6NDU6Ii9zdm5ibWovZWFybHkvMjAyNC8xMi8zMS9zdm4tMjAyNC0wMDM0NTEuYXRvbSI7fXM6ODoiZnJhZ21lbnQiO3M6MDoiIjt9) 

8.  Ahmed N, Wahlgren N, Grond M, et al. Implementation and outcome of thrombolysis with alteplase 3-4.5 h after an acute stroke: an updated analysis from SITS-ISTR. Lancet Neurol 2010;9:866–74. [doi:10.1016/S1474-4422(10)70165-4](http://dx.doi.org/10.1016/S1474-4422(10)70165-4)
    
    [CrossRef](http://svn.bmj.com/lookup/external-ref?access_num=10.1016/S1474-4422(10)70165-4&link_type=DOI) 
    
    [PubMed](http://svn.bmj.com/lookup/external-ref?access_num=20667790&link_type=MED&atom=%2Fsvnbmj%2Fearly%2F2024%2F12%2F31%2Fsvn-2024-003451.atom) 
    
    [Web of Science](http://svn.bmj.com/lookup/external-ref?access_num=000281465900007&link_type=ISI) 

9.  Liu L, Li Z, Zhou H, et al. Chinese stroke association guidelines for clinical management of ischaemic cerebrovascular diseases: executive summary and 2023 update. Stroke Vasc Neurol 2023;8:e002998. [doi:10.1136/svn-2023-002998](http://dx.doi.org/10.1136/svn-2023-002998)
    
    

10. Powers WJ, Rabinstein AA, Ackerson T, et al. Guidelines for the early management of patients with acute ischemic stroke: 2019 update to the 2018 guidelines for the early management of acute ischemic stroke: a guideline for healthcare professionals from the american heart association/american stroke association. Stroke 2019;50:e344–418. [doi:10.1161/STR.0000000000000211](http://dx.doi.org/10.1161/STR.0000000000000211)
    
    [CrossRef](http://svn.bmj.com/lookup/external-ref?access_num=10.1161/STR.0000000000000211&link_type=DOI) 
    
    [PubMed](http://svn.bmj.com/lookup/external-ref?access_num=31662037&link_type=MED&atom=%2Fsvnbmj%2Fearly%2F2024%2F12%2F31%2Fsvn-2024-003451.atom) 

11. Berge E, Whiteley W, Audebert H, et al. European stroke organisation (ESO) guidelines on intravenous thrombolysis for acute ischaemic stroke. Eur Stroke J 2021;6:I–LXII. [doi:10.1177/2396987321989865](http://dx.doi.org/10.1177/2396987321989865)
    
    

12. Gladstone DJ, Lindsay MP, Douketis J, et al. Canadian stroke best practice recommendations: secondary prevention of stroke update 2020. Can J Neurol Sci 2022;49:315–37. [doi:10.1017/cjn.2021.127](http://dx.doi.org/10.1017/cjn.2021.127)
    
    [CrossRef](http://svn.bmj.com/lookup/external-ref?access_num=10.1017/cjn.2021.127&link_type=DOI) 
    
    [PubMed](http://svn.bmj.com/lookup/external-ref?access_num=34140063&link_type=MED&atom=%2Fsvnbmj%2Fearly%2F2024%2F12%2F31%2Fsvn-2024-003451.atom) 

13. Wang Y, Wang Y, Zhao X, et al. Clopidogrel with aspirin in acute minor stroke or transient ischemic attack. N Engl J Med 2013;369:11–9. [doi:10.1056/NEJMoa1215340](http://dx.doi.org/10.1056/NEJMoa1215340)
    
    [CrossRef](http://svn.bmj.com/lookup/external-ref?access_num=10.1056/NEJMoa1215340&link_type=DOI) 
    
    [PubMed](http://svn.bmj.com/lookup/external-ref?access_num=23803136&link_type=MED&atom=%2Fsvnbmj%2Fearly%2F2024%2F12%2F31%2Fsvn-2024-003451.atom) 
    
    [Web of Science](http://svn.bmj.com/lookup/external-ref?access_num=000321263500006&link_type=ISI) 

14. Johnston SC, Easton JD, Farrant M, et al. Clopidogrel and aspirin in acute ischemic stroke and high-risk TIA. N Engl J Med 2018;379:215–25. [doi:10.1056/NEJMoa1800410](http://dx.doi.org/10.1056/NEJMoa1800410)
    
    [CrossRef](http://svn.bmj.com/lookup/external-ref?access_num=10.1056/NEJMoa1800410&link_type=DOI) 
    
    [PubMed](http://svn.bmj.com/lookup/external-ref?access_num=29766750&link_type=MED&atom=%2Fsvnbmj%2Fearly%2F2024%2F12%2F31%2Fsvn-2024-003451.atom) 

15. Khatri P, Kleindorfer DO, Devlin T, et al. Effect of alteplase vs aspirin on functional outcome for patients with acute ischemic stroke and minor nondisabling neurologic deficits: the PRISMS randomized clinical trial. JAMA 2018;320:156–66. [doi:10.1001/jama.2018.8496](http://dx.doi.org/10.1001/jama.2018.8496)
    
    [CrossRef](http://svn.bmj.com/lookup/external-ref?access_num=10.1001/jama.2018.8496&link_type=DOI) 
    
    [PubMed](http://svn.bmj.com/lookup/external-ref?access_num=29998337&link_type=MED&atom=%2Fsvnbmj%2Fearly%2F2024%2F12%2F31%2Fsvn-2024-003451.atom) 

16. Coutts SB, Ankolekar S, Appireddy R, et al. Tenecteplase versus standard of care for minor ischaemic stroke with proven occlusion (TEMPO-2): a randomised, open label, phase 3 superiority trial. Lancet 2024;16:8.
    
    

17. Fischer U, Baumgartner A, Arnold M, et al. What is a minor stroke? Stroke 2010;41:661–6. [doi:10.1161/STROKEAHA.109.572883](http://dx.doi.org/10.1161/STROKEAHA.109.572883)
    
    [Abstract/FREE Full Text](http://svn.bmj.com/lookup/ijlink/YTozOntzOjQ6InBhdGgiO3M6MTQ6Ii9sb29rdXAvaWpsaW5rIjtzOjU6InF1ZXJ5IjthOjQ6e3M6ODoibGlua1R5cGUiO3M6NDoiQUJTVCI7czoxMToiam91cm5hbENvZGUiO3M6OToic3Ryb2tlYWhhIjtzOjU6InJlc2lkIjtzOjg6IjQxLzQvNjYxIjtzOjQ6ImF0b20iO3M6NDU6Ii9zdm5ibWovZWFybHkvMjAyNC8xMi8zMS9zdm4tMjAyNC0wMDM0NTEuYXRvbSI7fXM6ODoiZnJhZ21lbnQiO3M6MDoiIjt9) 

18. Chen H-S, Cui Y, Zhou Z-H, et al. Dual antiplatelet therapy vs alteplase for patients with minor nondisabling acute ischemic stroke: the ARAMIS randomized clinical trial. JAMA 2023;329:2135–44. [doi:10.1001/jama.2023.7827](http://dx.doi.org/10.1001/jama.2023.7827)
    
    [PubMed](http://svn.bmj.com/lookup/external-ref?access_num=37367978&link_type=MED&atom=%2Fsvnbmj%2Fearly%2F2024%2F12%2F31%2Fsvn-2024-003451.atom) 

19. Nair R, Singh N, Kate M, et al. Intravenous tenecteplase compared with alteplase for minor ischaemic stroke: a secondary analysis of the act randomised clinical trial. Stroke Vasc Neurol 2024.:svn-2023-002828. [doi:10.1136/svn-2023-002828](http://dx.doi.org/10.1136/svn-2023-002828)
    
    

20. Gao Y, Pan Y, Han S, et al. Rationale and design of a randomised double-blind 2×2 factorial trial comparing the effect of a 3-month intensive statin and antiplatelet therapy for patients with acute mild ischaemic stroke or high-risk TIA with intracranial or extracranial atherosclerosis (INSPIRES). Stroke Vasc Neurol 2023;8:249–58. [doi:10.1136/svn-2022-002084](http://dx.doi.org/10.1136/svn-2022-002084)
    
    [Abstract/FREE Full Text](http://svn.bmj.com/lookup/ijlink/YTozOntzOjQ6InBhdGgiO3M6MTQ6Ii9sb29rdXAvaWpsaW5rIjtzOjU6InF1ZXJ5IjthOjQ6e3M6ODoibGlua1R5cGUiO3M6NDoiQUJTVCI7czoxMToiam91cm5hbENvZGUiO3M6Njoic3ZuYm1qIjtzOjU6InJlc2lkIjtzOjc6IjgvMy8yNDkiO3M6NDoiYXRvbSI7czo0NToiL3N2bmJtai9lYXJseS8yMDI0LzEyLzMxL3N2bi0yMDI0LTAwMzQ1MS5hdG9tIjt9czo4OiJmcmFnbWVudCI7czowOiIiO30=) 

21. Zi JS, Kong W, et al. Tirofiban for stroke without large or medium-sized vessel occlusion huang. N Engl J Med 2023;329:2025–36.
    
    

22. Chen H-S, Cui Y, Zhou Z-H, et al. Effect of argatroban plus intravenous alteplase vs intravenous alteplase alone on neurologic function in patients with acute ischemic stroke. JAMA 2023;329:640–50.
    
    [CrossRef](http://svn.bmj.com/lookup/external-ref?access_num=10.1001/jama.2023.0550&link_type=DOI) 
    
    [PubMed](http://svn.bmj.com/lookup/external-ref?access_num=36757755&link_type=MED&atom=%2Fsvnbmj%2Fearly%2F2024%2F12%2F31%2Fsvn-2024-003451.atom) 

23. Li X-Q, Cui Y, Wang X-H, et al. Early antiplatelet for minor stroke following thrombolysis (EAST): rationale and design. Int J Stroke 2023;18:615–9. [doi:10.1177/17474930221118900](http://dx.doi.org/10.1177/17474930221118900)
    
    [PubMed](http://svn.bmj.com/lookup/external-ref?access_num=35899772&link_type=MED&atom=%2Fsvnbmj%2Fearly%2F2024%2F12%2F31%2Fsvn-2024-003451.atom) 

24. Ingleton A, Raseta M, Chung R-E, et al. Is intraprocedural intravenous aspirin safe for patients who require emergent extracranial stenting during mechanical thrombectomy? Stroke Vasc Neurol 2023.:svn-2022-002267. [doi:10.1136/svn-2022-002267](http://dx.doi.org/10.1136/svn-2022-002267)
    
    

25. Wang Y, Li S, Zhou Q, et al. Vascular dementia has the highest hospitalisation rate in china: a nationwide hospital information system study. Stroke Vasc Neurol 2023;8:59–68. [doi:10.1136/svn-2022-001637](http://dx.doi.org/10.1136/svn-2022-001637)
    
    [Abstract/FREE Full Text](http://svn.bmj.com/lookup/ijlink/YTozOntzOjQ6InBhdGgiO3M6MTQ6Ii9sb29rdXAvaWpsaW5rIjtzOjU6InF1ZXJ5IjthOjQ6e3M6ODoibGlua1R5cGUiO3M6NDoiQUJTVCI7czoxMToiam91cm5hbENvZGUiO3M6Njoic3ZuYm1qIjtzOjU6InJlc2lkIjtzOjY6IjgvMS81OSI7czo0OiJhdG9tIjtzOjQ1OiIvc3ZuYm1qL2Vhcmx5LzIwMjQvMTIvMzEvc3ZuLTIwMjQtMDAzNDUxLmF0b20iO31zOjg6ImZyYWdtZW50IjtzOjA6IiI7fQ==) 

26. Leng X, Wang D. Minor stroke is not minor. Stroke Vasc Neurol 2023;8. [doi:10.1136/svn-2022-002285](http://dx.doi.org/10.1136/svn-2022-002285)
    
    

27. Rothwell PM, Giles MF, Chandratheva A, et al. Effect of urgent treatment of transient ischaemic attack and minor stroke on early recurrent stroke (EXPRESS study): a prospective population-based sequential comparison. The Lancet 2007;370:1432–42. [doi:10.1016/S0140-6736(07)61448-2](http://dx.doi.org/10.1016/S0140-6736(07)61448-2)
    
    

28. Adams HP, Bendixen BH, Kappelle LJ, et al. Classification of subtype of acute ischemic stroke. Definitions for use in a multicenter clinical trial. TOAST. Trial of Org 10172 in Acute Stroke Treatment. Stroke 1993;24:35–41. [doi:10.1161/01.str.24.1.35](http://dx.doi.org/10.1161/01.str.24.1.35)
    
    [Abstract/FREE Full Text](http://svn.bmj.com/lookup/ijlink/YTozOntzOjQ6InBhdGgiO3M6MTQ6Ii9sb29rdXAvaWpsaW5rIjtzOjU6InF1ZXJ5IjthOjQ6e3M6ODoibGlua1R5cGUiO3M6NDoiQUJTVCI7czoxMToiam91cm5hbENvZGUiO3M6OToic3Ryb2tlYWhhIjtzOjU6InJlc2lkIjtzOjc6IjI0LzEvMzUiO3M6NDoiYXRvbSI7czo0NToiL3N2bmJtai9lYXJseS8yMDI0LzEyLzMxL3N2bi0yMDI0LTAwMzQ1MS5hdG9tIjt9czo4OiJmcmFnbWVudCI7czowOiIiO30=) 

29. Butcher KS, Ng K, Sheridan P, et al. Dabigatran Treatment of Acute Noncardioembolic Ischemic Stroke. Stroke 2020;51:1190–8. [doi:10.1161/STROKEAHA.119.027569](http://dx.doi.org/10.1161/STROKEAHA.119.027569)
    
    [CrossRef](http://svn.bmj.com/lookup/external-ref?access_num=10.1161/STROKEAHA.119.027569&link_type=DOI) 
    
    [PubMed](http://svn.bmj.com/lookup/external-ref?access_num=32098609&link_type=MED&atom=%2Fsvnbmj%2Fearly%2F2024%2F12%2F31%2Fsvn-2024-003451.atom) 

30. Wang Y, Meng X, Wang A, et al. Ticagrelor versus Clopidogrel in CYP2C19 Loss-of-Function Carriers with Stroke or TIA. N Engl J Med 2021;385:2520–30. [doi:10.1056/NEJMoa2111749](http://dx.doi.org/10.1056/NEJMoa2111749)
    
    [CrossRef](http://svn.bmj.com/lookup/external-ref?access_num=10.1056/NEJMoa2111749&link_type=DOI) 
    
    [PubMed](http://svn.bmj.com/lookup/external-ref?access_num=34708996&link_type=MED&atom=%2Fsvnbmj%2Fearly%2F2024%2F12%2F31%2Fsvn-2024-003451.atom) 

31. Johnston SC, Amarenco P, Albers GW, et al. Ticagrelor versus Aspirin in Acute Stroke or Transient Ischemic Attack. N Engl J Med 2016;375:35–43. [doi:10.1056/NEJMoa1603060](http://dx.doi.org/10.1056/NEJMoa1603060)
    
    [CrossRef](http://svn.bmj.com/lookup/external-ref?access_num=10.1056/NEJMoa1603060&link_type=DOI) 
    
    [PubMed](http://svn.bmj.com/lookup/external-ref?access_num=27160892&link_type=MED&atom=%2Fsvnbmj%2Fearly%2F2024%2F12%2F31%2Fsvn-2024-003451.atom) 

32. Johnston SC, Amarenco P, Denison H, et al. Ticagrelor and Aspirin or Aspirin Alone in Acute Ischemic Stroke or TIA. N E J Med 2020;383:207–17. [doi:10.1056/NEJMoa1916870](http://dx.doi.org/10.1056/NEJMoa1916870)
    
    [CrossRef](http://svn.bmj.com/lookup/external-ref?access_num=10.1056/NEJMoa1916870&link_type=DOI) 
    
    [PubMed](http://svn.bmj.com/lookup/external-ref?access_num=http://www.n&link_type=MED&atom=%2Fsvnbmj%2Fearly%2F2024%2F12%2F31%2Fsvn-2024-003451.atom)