Skip to content
2000
Volume 22, Issue 2
  • ISSN: 1567-2026
  • E-ISSN: 1875-5739

Abstract

Introduction

High On-Treatment Platelet Reactivity (HTPR) is frequently observed after carotid endarterectomy (CEA) or stenting (CAS), but its association with adverse events remains uncertain. This systematic review and meta-analysis evaluate the association between HTPR and recurrent vascular events in these patients.

Methods

EMBASE, PubMed, and Cochrane Library were searched for eligible studies from inception to July 1, 2024. Two independent reviewers screened the records, extracted data, and assessed the bias using predefined criteria. A meta-analysis was conducted using RevMan 5.4 software. The primary outcome was the risk of recurrent ischemic events in patients with HTPR. Secondary outcomes included the risk of hemorrhage and carotid restenosis.

Results

Eight studies involving 1,052 patients were included in the meta-analysis. This meta-analysis found that HTPR significantly increased the risk of adverse vascular events (OR = 2.41, 95% CI: 1.37-4.24), particularly in CAS patients (OR = 1.85, 95% CI: 1.14-2.98), but not in CEA patients (OR = 4.53, 95% CI: 0.52-39.12). Furthermore, HTPR was not significantly associated with an increased risk of bleeding (OR = 0.90, 95% CI: 0.24-3.37) or carotid restenosis (OR = 1.70, 95% CI: 0.38-7.55).

Discussion

This meta-analysis demonstrates that HTPR may increase the risk of recurrent ischemic events in CAS patients, supporting the clinical utility of platelet function monitoring in this population. However, no significant association was observed between HTPR and hemorrhage or restenosis. These findings should be interpreted cautiously due to study limitations, including small sample sizes and heterogeneity in platelet function assessment methodologies. Large-scale prospective studies with standardized protocols are warranted to validate these observations.

Conclusion

HTPR may be associated with an increased risk of recurrent ischemic events in patients undergoing CAS, highlighting the potential value of platelet function monitoring.

Loading

Article metrics loading...

/content/journals/cnr/10.2174/0115672026395463250822065302
2025-08-27
2026-02-28
Loading full text...

Full text loading...

References

  1. RajagopalanS. MckayI. FordI. BachooP. GreavesM. BrittendenJ. Platelet activation increases with the severity of peripheral arterial disease: Implications for clinical management.J. Vasc. Surg.200746348549010.1016/j.jvs.2007.05.039 17826235
    [Google Scholar]
  2. ZhouK. YuS. LiJ. High on‐treatment platelet reactivity is associated with poor outcomes after ischemic stroke: A meta‐analysis.Acta Neurol. Scand.2022146320522410.1111/ane.13655 35652290
    [Google Scholar]
  3. GurbelP.A. BeckerR.C. MannK.G. SteinhublS.R. MichelsonA.D. Platelet function monitoring in patients with coronary artery disease.J. Am. Coll. Cardiol.200750191822183410.1016/j.jacc.2007.07.051 17980247
    [Google Scholar]
  4. MontenontE. EchagarrugaC. AllenN. AraldiE. SuarezY. BergerJ.S. Platelet WDR1 suppresses platelet activity and is associated with cardiovascular disease.Blood2016128162033204210.1182/blood‑2016‑03‑703157 27609643
    [Google Scholar]
  5. RaoZ. ZhengH. WangF. The association between high on-treatment platelet reactivity and early recurrence of ischemic events after minor stroke or TIA.Neurol. Res.201739871972610.1080/01616412.2017.1312793 28398139
    [Google Scholar]
  6. LvH. YangZ. WuH. High on-treatment platelet reactivity as predictor of long-term clinical outcomes in stroke patients with antiplatelet agents.Transl. Stroke Res.202213339139810.1007/s12975‑021‑00949‑7 34596891
    [Google Scholar]
  7. ShaikN.F. ReganR.F. NaikU.P. Platelets as drivers of ischemia/reperfusion injury after stroke.Blood Adv.2021551576158410.1182/bloodadvances.2020002888 33687431
    [Google Scholar]
  8. BraunwaldE AngiolilloD BatesE Assessing the current role of platelet function testing.Clin Cardiol200831S1I10I16(Suppl. 1)10.1002/clc.2036118481816
    [Google Scholar]
  9. GurbelP.A. BlidenK.P. HiattB.L. O’ConnorC.M. Clopidogrel for coronary stenting: Response variability, drug resistance, and the effect of pretreatment platelet reactivity.Circulation2003107232908291310.1161/01.CIR.0000072771.11429.83 12796140
    [Google Scholar]
  10. GalliM. TerracinaS. SchieraE. Interindividual variability in platelet reactivity among individuals with or without antiplatelet therapy: Results from a large tertiary care hospital.J. Thromb. Thrombolysis2024581718310.1007/s11239‑024‑03022‑w 39242457
    [Google Scholar]
  11. GrotemeyerK.H. ScharafinskiH.W. HusstedtI.W. Two-year follow-up of aspirin responder and aspirin non responder. A pilot-study including 180 post-stroke patients.Thromb. Res.199371539740310.1016/0049‑3848(93)90164‑J 8236166
    [Google Scholar]
  12. JeonS.B. SongH.S. KimB.J. Biochemical aspirin resistance and recurrent lesions in patients with acute ischemic stroke.Eur. Neurol.2010641515710.1159/000315147 20606449
    [Google Scholar]
  13. BuschL. SternM. DannenbergL. Impact of high on-treatment platelet reactivity after angioplasty in patients with peripheral arterial disease.Platelets202132339139710.1080/09537104.2020.1742314 32252582
    [Google Scholar]
  14. YangB. MaY. WangT. Carotid endarterectomy and stenting in a chinese population: Safety outcome of the revascularization of extracranial carotid artery stenosis trial.Transl. Stroke Res.202112223924710.1007/s12975‑020‑00835‑8 32686047
    [Google Scholar]
  15. FuH. HuP. MaC. PengF. HeZ. Association of clopidogrel high on-treatment reactivity with clinical outcomes and gene polymorphism in acute ischemic stroke patients.Medicine (Baltimore)20209915e1947210.1097/MD.0000000000019472 32282698
    [Google Scholar]
  16. FiolakiA. KatsanosA.H. KyritsisA.P. High on treatment platelet reactivity to aspirin and clopidogrel in ischemic stroke: A systematic review and meta-analysis.J. Neurol. Sci.201737611211610.1016/j.jns.2017.03.010 28431593
    [Google Scholar]
  17. WellsG.A. SheaB. O’ConnellD. PetersonJ. WelchV. LososM. The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses.Available from: https://www.ohri.ca/programs/clinical_epidemiology/oxford.asp.
  18. BallS.T.E. TaylorR. McCollumC.N. Resistance to antiplatelet therapy is associated with symptoms of cerebral ischemia in carotid artery disease.Vasc. Endovascular Surg.202054871271710.1177/1538574420947235 32856558
    [Google Scholar]
  19. CiolliL. LelliN. RosafioF. Platelet function monitoring performed after carotid stenting during endovascular stroke treatment predicts outcome.J. Stroke Cerebrovasc. Dis.202130710580010.1016/j.jstrokecerebrovasdis.2021.105800 33964545
    [Google Scholar]
  20. GonzálezA. MonicheF. CayuelaA. Gonzalez-MarcosJ.R. MayolA. MontanerJ. Antiplatelet effects of clopidogrel dose adjustment (75 mg/d vs 150 mg/d) after carotid stenting.J. Vasc. Surg.201460242843510.1016/j.jvs.2014.01.068 24629989
    [Google Scholar]
  21. MuramS. PanchendraboseK. EaglesM.E. Natural history of antiplatelet nonresponders undergoing carotid artery stenting.J. Neurosurg.2023139366166910.3171/2022.12.JNS222316 36708530
    [Google Scholar]
  22. NishiH. NakaharaI. MatsumotoS. Platelet reactivity and hemorrhage risk in neurointerventional procedures under dual antiplatelet therapy.J. Neurointerv. Surg.20168994995310.1136/neurintsurg‑2015‑011844 26297788
    [Google Scholar]
  23. SimonteG. GuglielminiG. FalcinelliE. High-on-treatment platelet reactivity predicts adverse outcome after carotid artery stenting: A prospective study.Thromb. Res.202322211712310.1016/j.thromres.2022.12.015 36640567
    [Google Scholar]
  24. YoshimuraM. SumitaK. FujiiS. Periprocedural variability of platelet functions in carotid artery stenting: An analysis using verifynow.J Neuroendovasc Ther202115850551610.5797/jnet.oa.2020‑0170 37502767
    [Google Scholar]
  25. LewszukA. StaszkiewiczaW. MadyckiG. SłowińskiP. Evaluation of platelet activity and incidence of resistance to acetylsalicylic acid in patients receiving thrombosis prevention after carotid endarterectomy.Acta Angiologica20121826878
    [Google Scholar]
  26. ChindaB. TranK.H. DoesburgS. Functional MRI evaluation of cognitive effects of carotid stenosis revascularization.Brain Behav.2022124e251210.1002/brb3.2512 35233977
    [Google Scholar]
  27. FuseY. KojimaT. ShintaiK. SekiY. Long-term outcomes of carotid artery stenting: A single-center experience.Neurol. Med. Chir. (Tokyo)202060312112510.2176/nmc.oa.2019‑0192 31902874
    [Google Scholar]
  28. NakagawaI KotsugiM YokoyamaS Antithrombotic therapy in carotid artery and intracranial artery stent.J Neuroendovasc Ther2025191ra.2024-001410.5797/jnet.ra.2024‑001440007971
    [Google Scholar]
  29. QajaE. TadiP. Theetha KariyannaP. Symptomatic Carotid Artery Stenosis.In: StatPearls.StatPearls Publishing2025
    [Google Scholar]
  30. StefaniniM. GaspariE. BoiL. Correlation between US-PSV and 64-Row MDCTA with advanced vessel analysis in the quantification of 50–70% carotid artery stenosis.Int. J. Vasc. Med.201220121810.1155/2012/928638 22577554
    [Google Scholar]
  31. CheF. MiD. WangA. Extracranial carotid plaque hemorrhage predicts ipsilateral stroke recurrence in patients with carotid atherosclerosis: A study based on high-resolution vessel wall imaging MRI.BMC Neurol.202222123710.1186/s12883‑022‑02758‑3 35764942
    [Google Scholar]
  32. KellyP.J. Camps-RenomP. GiannottiN. Carotid plaque inflammation imaged by 18 F-fluorodeoxyglucose positron emission tomography and risk of early recurrent stroke.Stroke20195071766177310.1161/STROKEAHA.119.025422 31167623
    [Google Scholar]
  33. JiangH. ZengQ. JiangW. Carotid-cavernous sinus fistula with primary clinical manifestation of cerebral infarction: Description of two cases.Quant. Imaging Med. Surg.20231332021202510.21037/qims‑22‑613 36915300
    [Google Scholar]
  34. KimM.J. HaS.K. Outcomes following carotid endarterectomy and carotid artery stenting in patients with carotid artery stenosis: A retrospective study from a single center in South Korea.Med. Sci. Monit.202329e93922310.12659/MSM.939223 36788720
    [Google Scholar]
  35. DucongeJ. Hernandez-SuarezD.F. Potential usefulness of clopidogrel pharmacogenetics in ce rebral endovascular procedures and carotid artery stenting.Curr. Clin. Pharmacol.2017121111710.2174/1574884712666170227154654 28245774
    [Google Scholar]
  36. HrbáčT. FiedlerJ. ProcházkaV. Comparison of carotid endarterectomy and repeated carotid angioplasty and stenting for in-stent restenosis (CERCAS trial): A randomised study.Stroke Vasc. Neurol.20238539940410.1136/svn‑2022‑002075 36972920
    [Google Scholar]
  37. BandykD.F. Follow-up after carotid endarterectomy and stenting: What to look for and why.Semin. Vasc. Surg.2020333-4475310.1053/j.semvascsurg.2020.11.001 33308595
    [Google Scholar]
  38. BonelloL. ManciniJ. PansieriM. Relationship between post‐treatment platelet reactivity and ischemic and bleeding events at 1‐year follow‐up in patients receiving prasugrel.J. Thromb. Haemost.201210101999200510.1111/j.1538‑7836.2012.04875.x 22863374
    [Google Scholar]
  39. TexakalidisP. GiannopoulosS. KokkinidisD.G. KarasavvidisT. Rangel-CastillaL. Reavey-CantwellJ. Carotid artery endarterectomy versus carotid artery stenting for patients with contralateral carotid occlusion: A systematic review and meta-analysis.World Neurosurg.2018120563571.e310.1016/j.wneu.2018.08.183 30189300
    [Google Scholar]
  40. MaoY. ZhuB. WenH. ZhongT. BianM. Impact of platelet hyperreactivity and diabetes mellitus on ischemic stroke recurrence: A single-center cohort clinical study.Int. J. Gen. Med.2024171127113810.2147/IJGM.S450059 38544974
    [Google Scholar]
  41. GoncalvesL.N. van VelzeV. KlokF.A. GalP. VosR.C. HammingJ.F. High on-treatment platelet reactivity in peripheral arterial disease: A systematic review.Vascular20231708538123121432410.1177/17085381231214324 37950666
    [Google Scholar]
  42. NohK.C. ChoiH. WooH.G. High-on-aspirin platelet reactivity differs between recurrent ischemic stroke associated with extracranial and intracranial atherosclerosis.J. Clin. Neurol.202218442142710.3988/jcn.2022.18.4.421 35796267
    [Google Scholar]
  43. WenM. LiY. QuX. Comparison of platelet reactivity between prasugrel and ticagrelor in patients with acute coronary syndrome: A meta-analysis.BMC Cardiovasc. Disord.202020143010.1186/s12872‑020‑01603‑0 33004000
    [Google Scholar]
  44. ČolićM.D. ČalijaB.M. MilosavljevićB.M. Low on‐treatment platelet reactivity predicts long‐term risk of bleeding after elective PCI.J. Interv. Cardiol.201528653154310.1111/joic.12251 26643001
    [Google Scholar]
  45. AradiD. KirtaneA. BonelloL. Bleeding and stent thrombosis on P2Y 12 -inhibitors: collaborative analysis on the role of platelet reactivity for risk stratification after percutaneous coronary intervention.Eur. Heart J.201536271762177110.1093/eurheartj/ehv104 25896078
    [Google Scholar]
  46. GruttemeierJ. CottinY. YaoH. Impact of platelet reactivity in ACS patients on clinical outcomes with triple antithrombotic therapy.J. Clin. Med.2021108156510.3390/jcm10081565 33917717
    [Google Scholar]
  47. SibbingD. SteinhublS.R. SchulzS. SchömigA. KastratiA. Platelet aggregation and its association with stent thrombosis and bleeding in clopidogrel-treated patients: Initial evidence of a therapeutic window.J. Am. Coll. Cardiol.201056431731810.1016/j.jacc.2010.03.048 20633826
    [Google Scholar]
  48. MichelsonA.D. FrelingerA.L. FurmanM.I. Current options in platelet function testing.Am. J. Cardiol.20069810S4S1010.1016/j.amjcard.2006.09.008 17097417
    [Google Scholar]
  49. LarsenJ.B. HvasA.M. HojbjergJ.A. Platelet function testing: Update and future directions.Semin. Thromb. Hemost.202349660060810.1055/s‑0042‑1757898 36384230
    [Google Scholar]
  50. GebetsbergerJ. PrüllerF. Classic light transmission platelet aggregometry: Do we still need it?Hamostaseologie202444430431510.1055/a‑2117‑4614 38065556
    [Google Scholar]
/content/journals/cnr/10.2174/0115672026395463250822065302
Loading
/content/journals/cnr/10.2174/0115672026395463250822065302
Loading

Data & Media loading...

Supplements

PRISMA checklist is available as supplementary material on the publisher’s website along with the published article.


  • Article Type:
    Research Article
Keyword(s): carotid artery endarterectomy; Carotid artery stenting; CAS; CEA; HTPR; platelet reactivity
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test