Skip to main content

Advertisement

Log in

Triple antiplatelet therapy with addition of cilostazol to aspirin and clopidogrel for Y-stent-assisted coil embolization of cerebral aneurysms

  • Clinical Article - Vascular
  • Published:
Acta Neurochirurgica Aims and scope Submit manuscript

Abstract

Background

Dual antiplatelet therapy for stent-assisted coiling of cerebral aneurysms is essential to prevent thromboembolic complications. There is concern that Y-stent-assisted coiling may increase thromboembolic complications compared with coiling with a single stent. Several reports have demonstrated that cilostazol may improve clopidogrel responsiveness. We investigated whether triple antiplatelet therapy with addition of cilostazol to aspirin plus clopidogrel for Y-stents can prevent thromboembolic events.

Methods

Between July 2010 and October 2012, we treated 40 consecutive aneurysms with coil embolization using Enterprise stents. At the peri-procedural period, dual antiplatelet agents (100 mg aspirin and 75 mg clopidogrel) were used for the single stent group (n = 36), and triple antiplatelet agents (addition of 200 mg cilostazol) were used for the Y-stent group (n = 4). We evaluated post-operative diffusion-weighted imaging (DWI) and any complications. We assessed the following for statistical analysis: age, sex, aneurysm location, shape, and size, neck size, size of parent vessels, and stent length.

Results

We found two neurological peri-procedural complications: one transient ischemic attack and one infarction. Both complications belonged to the Y-stent group, which was a significant factor of thromboembolic events (P = 0.008). There were no other significant factors related to neurological complications or positive DWI. For subgroup analysis of the single stent group, stent length was significantly longer in positive DWI than negative DWI (P = 0.04). In the follow-up period of 20 ± 8.6 months, there were no symptomatic late complications in any patients.

Conclusions

Although the number of patients in the Y-stent group is small, this group had a significantly higher risk of thromboembolic complications. While our protocol of a routine dose of dual antiplatelet therapy may be sufficient for single stent therapy, our protocol of a routine dose of triple antiplatelet therapy for Y-stents may not prevent thromboembolic events. This suggests that evaluation of platelet function may be essential, especially for Y-stents.

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

Access this article

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

Instant access to the full article PDF.

Fig. 1

Similar content being viewed by others

References

  1. Akgul E, Aksungur E, Balli T, Onan B, Yilmaz DM, Bicakci S, Erman T (2011) Y-stent-assisted coil embolization of wide-neck intracranial aneurysms. A single center experience. Interv Neuroradiol 17:36–48

    PubMed  CAS  Google Scholar 

  2. Albayram S, Selcuk H, Kara B, Bozdag E, Uzma O, Kocer N, Islak C (2004) Thromboembolic events associated with balloon-assisted coil embolization: evaluation with diffusion-weighted MR imaging. AJNR Am J Neuroradiol 25:1768–1777

    PubMed  Google Scholar 

  3. Capranzano P, Ferreiro JL, Ueno M, Capodanno D, Dharmashankar K, Darlington A, Desai B, Tello-Montoliu A, Rollini F, Angiolillo DJ (2013) Pharmacodynamic effects of adjunctive cilostazol therapy in patients with coronary artery disease on dual antiplatelet therapy: impact of high on-treatment platelet reactivity and diabetes mellitus status. Catheter Cardiovasc Interv 81:42–49

    Article  PubMed  Google Scholar 

  4. Cekirge HS, Yavuz K, Geyik S, Saatci I (2011) A novel “Y” stent flow diversion technique for the endovascular treatment of bifurcation aneurysms without endosaccular coiling. AJNR Am J Neuroradiol 32:1262–1268

    Article  PubMed  CAS  Google Scholar 

  5. Chalouhi N, Jabbour P, Gonzalez LF, Dumont AS, Rosenwasser R, Starke RM, Gordon D, Hann S, Tjoumakaris S (2012) Safety and efficacy of endovascular treatment of basilar tip aneurysms by coiling with and without stent-assistance: a review of 235 cases. Neurosurgery 71:785–794

    Article  PubMed  Google Scholar 

  6. Delgado Almandoz JE, Crandall BM, Scholz JM, Fease JL, Anderson RE, Kadkhodayan Y, Tubman DE (2013) Pre-procedure P2Y12 reaction units value predicts perioperative thromboembolic and hemorrhagic complications in patients with cerebral aneurysms treated with the Pipeline Embolization Device. J Neurointerv Surg. doi:10.1136/neurintsurg-2012-010582

    Google Scholar 

  7. Feher G, Feher A, Pusch G, Koltai K, Tibold A, Gasztonyi B, Papp E, Szapary L, Kesmarky G, Toth K (2010) Clinical importance of aspirin and clopidogrel resistance. World J Cardiol 2:171–186

    Article  PubMed  Google Scholar 

  8. Gasparyan AY, Watson T, Lip GY (2008) The role of aspirin in cardiovascular prevention: implications of aspirin resistance. J Am Coll Cardiol 51:1829–1843

    Article  PubMed  CAS  Google Scholar 

  9. Godino C, Mendolicchio L, Figini F, Latib A, Sharp AS, Cosgrave J, Calori G, Cera M, Chieffo A, Castelli A, Maseri A, Ruggeri ZM, Colombo A (2009) Comparison of VerifyNow-P2Y12 test and Flow Cytometry for monitoring individual platelet response to clopidogrel. What is the cut-off value for identifying patients who are low responders to clopidogrel therapy? Thromb J 7:4

    Article  PubMed  Google Scholar 

  10. Haraguchi K, Miyachi S, Izumi T, Matsubara N, Naito T, Asai T, Yamanouchi T, Wakabayashi T (2012) Resistance to antiplatelet agents assessed by a point-of-care platelet function test and thromboembolic adverse events in neurointervention. No Shinkei Geka 40:399–406

    PubMed  CAS  Google Scholar 

  11. Heller RS, Miele WR, Do-Dai DD, Malek AM (2011) Crescent sign on magnetic resonance angiography revealing incomplete stent apposition: correlation with diffusion-weighted changes in stent-mediated coil embolization of aneurysms. J Neurosurg 115:624–632

    Article  PubMed  Google Scholar 

  12. Jin EZ, Yu LH, Li XQ (2012) Loading effect of 200 mg cilostazol on platelet inhibition in patients undergoing percutaneous coronary intervention. Int Heart J 53:1–4

    Article  PubMed  CAS  Google Scholar 

  13. Kang DH, Hwang YH, Kim YS, Bae GY, Lee SJ (2013) Cognitive outcome and clinically silent thromboembolic events after coiling of asymptomatic unruptured intracranial aneurysm. Neurosurgery 72:638–645

    Article  PubMed  Google Scholar 

  14. Kang DH, Kim BM, Kim DJ, Suh SH, Kim DI, Kim YS, Huh SK, Park J, Lee JW, Kim YB (2013) MR-DWI-positive lesions and symptomatic ischemic complications after coiling of unruptured intracranial aneurysms. Stroke 44:789–791

    Article  PubMed  Google Scholar 

  15. Kang HS, Kwon BJ, Kim JE, Han MH (2010) Preinterventional clopidogrel response variability for coil embolization of intracranial aneurysms: clinical implications. AJNR Am J Neuroradiol 31:1206–1210

    Article  PubMed  Google Scholar 

  16. Kono K, Shintani A, Tanaka Y, Terada T (2013) Delayed in-stent occlusion due to stent-related changes in vascular geometry after cerebral aneurysm treatment. Neurol Med Chir (Tokyo) 53:182–185

    Article  Google Scholar 

  17. Kono K, Terada T (2013) Hemodynamics of 8 different configurations of stenting for bifurcation aneurysms. AJNR Am J Neuroradiol. doi:10.3174/ajnr.A3479

    PubMed  Google Scholar 

  18. Krasopoulos G, Brister SJ, Beattie WS, Buchanan MR (2008) Aspirin “resistance” and risk of cardiovascular morbidity: systematic review and meta-analysis. BMJ 336:195–198

    Article  PubMed  Google Scholar 

  19. Lee DH, Arat A, Morsi H, Shaltoni H, Harris JR, Mawad ME (2008) Dual antiplatelet therapy monitoring for neurointerventional procedures using a point-of-care platelet function test: a single-center experience. AJNR Am J Neuroradiol 29:1389–1394

    Article  PubMed  CAS  Google Scholar 

  20. Lee GY, Hahn JY, Lee SY, Kim HJ, Kim JH, Lee SY, Song YB, Choi SH, Choi JH, Gwon HC (2013) Adjunctive cilostazol versus high maintenance dose of clopidogrel in patients with hyporesponsiveness to chronic clopidogrel therapy. Yonsei Med J 54:34–40

    Article  PubMed  CAS  Google Scholar 

  21. Lozen A, Manjila S, Rhiew R, Fessler R (2009) Y-stent-assisted coil embolization for the management of unruptured cerebral aneurysms: report of six cases. Acta Neurochir (Wien) 151:1663–1672

    Article  Google Scholar 

  22. Maruyama H, Takeda H, Dembo T, Nagoya H, Kato Y, Fukuoka T, Deguchi I, Horiuchi Y, Tanahashi N (2011) Clopidogrel resistance and the effect of combination cilostazol in patients with ischemic stroke or carotid artery stenting using the VerifyNow P2Y12 Assay. Intern Med 50:695–698

    Article  PubMed  CAS  Google Scholar 

  23. de Miguel CA, Cuellas Ramón C, Diego Nieto A, Samaniego Lampón B, Alonso Rodríguez D, Fernández Vázquez F, Alonso Orcajo N, Carbonell de Blas R, Pascual Vicente C, Pérez de Prado A (2009) Post-treatment platelet reactivity predicts long-term adverse events better than the response to clopidogrel in patients with non-ST-segment elevation acute coronary syndrome. Rev Esp Cardiol 62:126–135

    Article  Google Scholar 

  24. Patrono C, García Rodríguez LA, Landolfi R, Baigent C (2005) Low-dose aspirin for the prevention of atherothrombosis. N Engl J Med 353:2373–2383

    Article  PubMed  CAS  Google Scholar 

  25. Piotin M, Blanc R, Spelle L, Mounayer C, Piantino R, Schmidt PJ, Moret J (2010) Stent-assisted coiling of intracranial aneurysms: clinical and angiographic results in 216 consecutive aneurysms. Stroke 41:110–115

    Article  PubMed  Google Scholar 

  26. Price MJ, Berger PB, Teirstein PS, Tanguay JF, Angiolillo DJ, Spriggs D, Puri S, Robbins M, Garratt KN, Bertrand OF, Stillabower ME, Stillablower ME, Aragon JR, Kandzari DE, Stinis CT, Lee MS, Manoukian SV, Cannon CP, Schork NJ, Topol EJ, Investigators GRAVITAS (2011) Standard- vs high-dose clopidogrel based on platelet function testing after percutaneous coronary intervention: the GRAVITAS randomized trial. JAMA 305:1097–1105

    Article  PubMed  CAS  Google Scholar 

  27. Rogers KC, Faircloth JM, Finks SW (2012) Use of cilostazol in percutaneous coronary interventions. Ann Pharmacother 46:839–850

    Article  PubMed  Google Scholar 

  28. Rohde S, Bendszus M, Hartmann M, Hähnel S (2010) Treatment of a wide-necked aneurysm of the anterior cerebral artery using two Enterprise stents in “Y”-configuration stenting technique and coil embolization: a technical note. Neuroradiology 52:231–235

    Article  PubMed  Google Scholar 

  29. Rordorf G, Bellon RJ, Budzik RE, Farkas J, Reinking GF, Pergolizzi RS, Ezzeddine M, Norbash AM, Gonzalez RG, Putman CM (2001) Silent thromboembolic events associated with the treatment of unruptured cerebral aneurysms by use of Guglielmi detachable coils: prospective study applying diffusion-weighted imaging. AJNR Am J Neuroradiol 22:5–10

    PubMed  CAS  Google Scholar 

  30. Sim SY, Shin YS (2012) Silent microembolism on diffusion-weighted MRI after coil embolization of cerebral aneurysms. Neurointervention 7:77–84

    Article  PubMed  Google Scholar 

  31. Smith SC, Feldman TE, Hirshfeld JW, Jacobs AK, Kern MJ, King SB, Morrison DA, O’Neill WW, Schaff HV, Whitlow PL, Williams DO, Antman EM, Smith SC, Adams CD, Anderson JL, Faxon DP, Fuster V, Halperin JL, Hiratzka LF, Hunt SA, Jacobs AK, Nishimura R, Ornato JP, Page RL, Riegel B, ACC/AHA/SCAI Writing Committee to Update the 2001 Guidelines for Percutaneous Coronary Intervention (2006) ACC/AHA/SCAI 2005 guideline update for percutaneous coronary intervention: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (ACC/AHA/SCAI Writing Committee to Update the 2001 Guidelines for Percutaneous Coronary Intervention). J Am Coll Cardiol 47:e1–e121

    Article  PubMed  Google Scholar 

  32. Snoep JD, Hovens MM, Eikenboom JC, van der Bom JG, Jukema JW, Huisman MV (2007) Clopidogrel nonresponsiveness in patients undergoing percutaneous coronary intervention with stenting: a systematic review and meta-analysis. Am Heart J 154:221–231

    Article  PubMed  CAS  Google Scholar 

  33. Thorell WE, Chow MM, Woo HH, Masaryk TJ, Rasmussen PA (2005) Y-configured dual intracranial stent-assisted coil embolization for the treatment of wide-necked basilar tip aneurysms. Neurosurgery 56:1035–1040

    PubMed  Google Scholar 

  34. Tran HA, Anand SS, Hankey GJ, Eikelboom JW (2007) Aspirin resistance. Thromb Res 120:337–346

    Article  PubMed  CAS  Google Scholar 

  35. Wakhloo AK, Linfante I, Silva CF, Samaniego EA, Dabus G, Etezadi V, Spilberg G, Gounis MJ (2012) Closed-cell stent for coil embolization of intracranial aneurysms: clinical and angiographic results. AJNR Am J Neuroradiol 33:1651–1656

    Article  PubMed  CAS  Google Scholar 

  36. Zhao KJ, Yang PF, Huang QH, Li Q, Zhao WY, Liu JM, Hong B (2012) Y-configuration stent placement (crossing and kissing) for endovascular treatment of wide-neck cerebral aneurysms located at 4 different bifurcation sites. AJNR Am J Neuroradiol 33:1310–1316

    Article  PubMed  Google Scholar 

Download references

Conflicts of interest

None.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Kenichi Kono.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kono, K., Shintani, A., Yoshimura, R. et al. Triple antiplatelet therapy with addition of cilostazol to aspirin and clopidogrel for Y-stent-assisted coil embolization of cerebral aneurysms. Acta Neurochir 155, 1549–1557 (2013). https://doi.org/10.1007/s00701-013-1771-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00701-013-1771-4

Keywords

Navigation