Skip to main content
SpringerLink
Log in

Ticagrelor versus clopidogrel in dual antiplatelet therapy after minor stroke or transient ischemic attack: an updated network meta-analysis

  • Review
  • Published:
Journal of Neurology Aims and scope Submit manuscript

Abstract

Background

Dual antiplatelet therapy (DAPT) with clopidogrel plus aspirin is a well-established practice after a minor stroke or transient ischemic attack (TIA). However, ticagrelor plus aspirin may be an alternative.

Aims

We systematically searched PubMed, Embase, and Cochrane Central from inception to January 2024. We included randomized controlled trials (RCTs) enrolling adults with acute minor stroke or TIA within 72 hours of the onset of the symptoms.

Results

A total of 8 RCTs were included in our meta-analysis. Ticagrelor plus aspirin (RR, 0.70; 95% CrI 0.52, 0.91) and clopidogrel plus aspirin (RR, 0.79; 95% CrI 0.64, 0.98) were superior to aspirin in preventing stroke recurrence in overall analysis. Excluding studies with dual antiplatelet up to 90 days, ticagrelor plus aspirin was the only strategy that maintained superiority compared with aspirin regarding stroke recurrence (RR, 0.70; 95% CrI 0.51, 0.95) and ischemic stroke (RR, 0.68; 95% CrI 0.47, 0.94). There was no significant difference between treatment groups regarding hemorrhagic stroke, functional disability, and mortality.

Conclusions

DAPTs were superior to aspirin in preventing recurrence or ischemic stroke. Although no significant difference was observed between DAPTs, ticagrelor plus aspirin may be related to worse major bleeding results, including intracranial bleeding. Ticagrelor plus aspirin is a considerable option for patients after a minor stroke or TIA.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

Data availability

Data availability does not apply to this article as no new data were created or analyzed in this study.

Abbreviations

TIA:

Transient ischemic attack

AHA:

American Heart Association

ESO:

European Stroke Organization

DAPT:

Dual antiplatelet therapy

THALES:

Acute Stroke or Transient Ischemic Attack Treated With Ticagrelor and ASA for Prevention of Stroke and Death

INSPIRES:

Intensive Statin and Antiplatelet Therapy for Acute High-Risk Intracranial or Extracranial Atherosclerosis

NMA:

Network meta-analysis

PRISMA:

Preferred Reporting Items for Systematic Reviews and Meta-analysis

PROSPERO:

International prospective register of systematic reviews

RCT:

Randomized controlled trial

NIHSS:

National Institutes of Health Score Scale

RoB 2:

Cochrane risk-of-bias tool for randomized trials

RR:

Risk ratio

CrI:

Credible intervals

SUCRA:

Surface under the cumulative rank curves

CHANCE-2:

Ticagrelor or Clopidogrel with Aspirin in High-Risk Patients with Acute Nondisabling Cerebrovascular Events II

POINT:

Platelet-Oriented Inhibition in New TIA and Minor Ischemic Stroke

FASTER:

Fast Assessment of Stroke and Transient Ischaemic Attack to Prevent Early Recurrence

References

  1. Coutts SB, Hill MD, Campos CR et al (2008) Recurrent events in transient ischemic attack and minor stroke: what events are happening and to which patients? Stroke 39:2461–2466. https://doi.org/10.1161/STROKEAHA.107.513234

    Article  PubMed  Google Scholar 

  2. Rothwell PM, Buchan A, Johnston SC (2006) Recent advances in management of transient ischaemic attacks and minor ischaemic strokes. Lancet Neurol 5:323–331. https://doi.org/10.1016/S1474-4422(06)70408-2

    Article  PubMed  Google Scholar 

  3. Powers WJ, Rabinstein AA, Ackerson T et al (2019) 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. https://doi.org/10.1161/STR.0000000000000211

    Article  PubMed  Google Scholar 

  4. Dawson J, Merwick Á, Webb A et al (2021) European Stroke Organisation expedited recommendation for the use of short-term dual antiplatelet therapy early after minor stroke and high-risk TIA. Eur Stroke J 6:CLXXXVII–CXCL. https://doi.org/10.1177/23969873211000877

    Article  PubMed  PubMed Central  Google Scholar 

  5. Turan TN, Zaidat OO, Gronseth GS et al (2022) Stroke prevention in symptomatic large artery intracranial atherosclerosis practice advisory: report of the AAN guideline subcommittee. Neurology 98:486–498. https://doi.org/10.1212/WNL.0000000000200030

    Article  PubMed  PubMed Central  Google Scholar 

  6. Psychogios M, Brehm A, López-Cancio E et al (2022) European Stroke Organisation guidelines on treatment of patients with intracranial atherosclerotic disease. Eur Stroke J 7:XLII–LXXX. https://doi.org/10.1177/23969873221099715

    Article  Google Scholar 

  7. Husted S, Emanuelsson H, Heptinstall S et al (2006) Pharmacodynamics, pharmacokinetics, and safety of the oral reversible P2Y12 antagonist AZD6140 with aspirin in patients with atherosclerosis: a double-blind comparison to clopidogrel with aspirin. Eur Heart J 27:1038–1047. https://doi.org/10.1093/eurheartj/ehi754

    Article  CAS  PubMed  Google Scholar 

  8. Wang Y, Meng X, Wang A et al (2021) Ticagrelor versus clopidogrel in CYP2C19 loss-of-function carriers with stroke or TIA. N Engl J Med 385:2520–2530. https://doi.org/10.1056/NEJMoa2111749

    Article  CAS  PubMed  Google Scholar 

  9. Johnston SC, Amarenco P, Denison H et al (2020) Ticagrelor and aspirin or aspirin alone in acute ischemic stroke or TIA. N Engl J Med 383:207–217. https://doi.org/10.1056/NEJMoa1916870

    Article  CAS  PubMed  Google Scholar 

  10. Gao Y, Chen W, Pan Y et al (2023) Dual antiplatelet treatment up to 72 hours after ischemic stroke. N Engl J Med 389:2413–2424. https://doi.org/10.1056/NEJMoa2309137

    Article  CAS  PubMed  Google Scholar 

  11. Klein MD, Williams AK, Lee CR, Stouffer GA (2019) Clinical utility of CYP2C19 genotyping to guide antiplatelet therapy in patients with an acute coronary syndrome or undergoing percutaneous coronary intervention. ATVB 39:647–652. https://doi.org/10.1161/ATVBAHA.118.311963

    Article  CAS  Google Scholar 

  12. Li M, Yang Q, Shi J et al (2023) Ticagrelor plus aspirin in patients with minor ischemic stroke and transient ischemic attack: a network meta-analysis. BMC Neurol 23:303. https://doi.org/10.1186/s12883-023-03356-7

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Lun R, Dhaliwal S, Zitikyte G et al (2022) Comparison of ticagrelor vs clopidogrel in addition to aspirin in patients with minor ischemic stroke and transient ischemic attack: a network meta-analysis. JAMA Neurol 79:141. https://doi.org/10.1001/jamaneurol.2021.4514

    Article  PubMed  Google Scholar 

  14. Lun R, Zitikyte G, Roy DC et al (2023) Dual antiplatelet therapy in minor stroke/transient ischemic attack—an updated network meta-analysis. Can J Neurol Sci. https://doi.org/10.1017/cjn.2023.287

    Article  PubMed  Google Scholar 

  15. Higgins JPT, Thomas J, Chandler J, Cumpston M, Li T, Page MJ, Welch VA (eds) (2022) Cochrane Handbook for Systematic Reviews of Interventions version 6.3 (updated February 2022). Cochrane. www.training.cochrane.org/handbook

  16. Moher D, Liberati A, Tetzlaff J et al (2009) Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. BMJ 339:b2535–b2535. https://doi.org/10.1136/bmj.b2535

    Article  PubMed  PubMed Central  Google Scholar 

  17. Sterne JAC, Savović J, Page MJ et al (2019) RoB 2: a revised tool for assessing risk of bias in randomised trials. BMJ 366:l4898. https://doi.org/10.1136/bmj.l4898

    Article  PubMed  Google Scholar 

  18. Harrer M, Cuijpers P, Furukawa TA, Ebert DD (2021) Doing meta-analysis in R. https://bookdown.org/MathiasHarrer/Doing_Meta_Analysis_in_R/ Accessed 29 Apr 2021

  19. Salanti G, Ades AE, Ioannidis JPA (2011) Graphical methods and numerical summaries for presenting results from multiple-treatment meta-analysis: an overview and tutorial. J Clin Epidemiol 64:163–171. https://doi.org/10.1016/j.jclinepi.2010.03.016

    Article  PubMed  Google Scholar 

  20. Tonin FS, Rotta I, Mendes AM, Pontarolo R (2017) Network meta-analysis: a technique to gather evidence from direct and indirect comparisons. Pharm Pract (Granada) 15:943–943. https://doi.org/10.18549/PharmPract.2017.01.943

    Article  PubMed  Google Scholar 

  21. Dias S, Welton NJ, Sutton AJ, Caldwell DM, Lu G, Ades AE (2021) NICE DSU technical support document 4: inconsistency in networks of evidence based on randomised controlled trials. https://research-information.bris.ac.uk/en/publications/nice-dsu-technical-support-document-4-inconsistency-in-networks-o Accessed 10 Mar 2021

  22. Brooks SP, Gelman A (1998) General methods for monitoring convergence of iterative simulations. J Comput Graph Stat 7:434–455. https://doi.org/10.1080/10618600.1998.10474787

    Article  Google Scholar 

  23. Béliveau A, Boyne DJ, Slater J et al (2019) BUGSnet: an R package to facilitate the conduct and reporting of Bayesian network Meta-analyses. BMC Med Res Methodol 19:196. https://doi.org/10.1186/s12874-019-0829-2

    Article  PubMed  PubMed Central  Google Scholar 

  24. Johnston SC, Easton JD, Farrant M et al (2018) Clopidogrel and aspirin in acute ischemic stroke and high-risk TIA. N Engl J Med 379:215–225. https://doi.org/10.1056/NEJMoa1800410

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Johnston SC, Amarenco P, Albers GW et al (2016) Ticagrelor versus aspirin in acute stroke or transient ischemic attack. N Engl J Med 375:35–43. https://doi.org/10.1056/NEJMoa1603060

    Article  CAS  PubMed  Google Scholar 

  26. Wang Y, Wang Y, Zhao X et al (2013) Clopidogrel with aspirin in acute minor stroke or transient ischemic attack. N Engl J Med 369:11–19. https://doi.org/10.1056/NEJMoa1215340

    Article  CAS  PubMed  Google Scholar 

  27. Wang Y, Chen W, Lin Y et al (2019) Ticagrelor plus aspirin versus clopidogrel plus aspirin for platelet reactivity in patients with minor stroke or transient ischaemic attack: open label, blinded endpoint, randomised controlled phase II trial. BMJ 365:l2211. https://doi.org/10.1136/bmj.l2211

    Article  PubMed  PubMed Central  Google Scholar 

  28. Kennedy J, Hill MD, Ryckborst KJ et al (2007) Fast assessment of stroke and transient ischaemic attack to prevent early recurrence (FASTER): a randomised controlled pilot trial. Lancet Neurol 6:961–969. https://doi.org/10.1016/S1474-4422(07)70250-8

    Article  CAS  PubMed  Google Scholar 

  29. Pan Y, Elm JJ, Li H et al (2019) Outcomes associated with clopidogrel-aspirin use in minor stroke or transient ischemic attack: a pooled analysis of clopidogrel in high-risk patients with acute non-disabling cerebrovascular events (CHANCE) and platelet-oriented inhibition in new tia and minor ischemic stroke (POINT) trials. JAMA Neurol 76:1466. https://doi.org/10.1001/jamaneurol.2019.2531

    Article  PubMed  PubMed Central  Google Scholar 

  30. Mbuagbaw L, Rochwerg B, Jaeschke R et al (2017) Approaches to interpreting and choosing the best treatments in network meta-analyses. Syst Rev 6:79. https://doi.org/10.1186/s13643-017-0473-z

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Moore JM, Adeeb N, Shallwani H et al (2017) A multicenter cohort comparison study of the safety, efficacy, and cost of ticagrelor compared to clopidogrel in aneurysm flow diverter procedures. Neurosurgery 81:665–671. https://doi.org/10.1093/neuros/nyx079

    Article  PubMed  Google Scholar 

  32. Narasimhalu K, Chan J, Ang YK et al (2024) Empiric treatment with aspirin and ticagrelor is the most cost-effective strategy in patients with minor stroke or transient ischemic attack. Int J Stroke 19:209–216. https://doi.org/10.1177/17474930231202374

    Article  PubMed  Google Scholar 

Download references

Funding

There were no external funding sources for this study.

Author information

Author notes

  1. The authors Gabriel Marinheiro, Beatriz Araújo and Gabriel de Almeida Monteiro have contributed equally to this work.

Authors and Affiliations

  1. School of Medicine, Federal University of Ceará, Sobral, Brazil

    Gabriel Marinheiro & Gabriel de Almeida Monteiro

  2. Department of Medicine, Nove de Julho University, São Bernardo do Campo, Brazil

    Beatriz Araújo & André Rivera

  3. Department of Neurosurgery, Federal University of Ceará, Sobral, Brazil

    Joaquim Francisco Cavalcante-Neto

  4. School of Medicine, Santa Marcelina College, São Paulo, Brazil

    Marianna Leite

  5. School of Medicine, Federal University of Minas Gerais, Belo Horizonte, Brazil

    Antonio Mutarelli

  6. Federal University of Mato Grosso, Sinop, Brazil

    Artur Menegaz de Almeida

  7. Department of Neurology, Brigham and Women’s Hospital, Massachusetts General Hospital, Harvard Medical School, Boston, USA

    Agostinho C. Pinheiro

  8. Department of Internal Medicine, Icahn School of Medicine at Mount Sinai, Elmhurst Hospital Center, New York, USA

    Agostinho C. Pinheiro

  9. Department of Neurology, University of São Paulo, São Paulo, Brazil

    João Paulo Mota Telles

Authors
  1. Gabriel Marinheiro
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Beatriz Araújo
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Gabriel de Almeida Monteiro
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Marianna Leite
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Antonio Mutarelli
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Artur Menegaz de Almeida
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Joaquim Francisco Cavalcante-Neto
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. André Rivera
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Agostinho C. Pinheiro
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. João Paulo Mota Telles
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

GM contributed to conception and design, study selection, data acquisition, data analysis, writing the initial draft, review, editing, and figures; BA was responsible for data acquisition, data analysis, writing the initial draft, editing, and figures; GAM was involved in data acquisition, data analysis, writing draft, editing, and figures; ML performed data acquisition, data analysis, and writing draft; AM performed data acquisition and writing draft; AMA was involved in data acquisition, risk of bias assessment, and writing draft; JFC-N did data acquisition, review, and writing draft; AR was involved in data acquisition, review, and writing draft; ACP contributed to conception, design, and review; and JPMT contributed to conception and design, editing, and review.

Corresponding author

Correspondence to Gabriel Marinheiro.

Ethics declarations

Conflicts of interest

The authors have no conflict of interest to declare.

Ethical approval

This is a systematic review and meta-analysis. No ethical approval was required as no new patient data were collected.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (DOCX 1664 KB)

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Marinheiro, G., Araújo, B., Monteiro, G.A. et al. Ticagrelor versus clopidogrel in dual antiplatelet therapy after minor stroke or transient ischemic attack: an updated network meta-analysis. J Neurol (2024). https://doi.org/10.1007/s00415-024-12330-3

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s00415-024-12330-3

Keywords

Search

Navigation