Skip to main content
Log in

Tailoring clopidogrel dose according to multiple electrode aggregometry decreases the rate of ischemic complications after percutaneous coronary intervention

  • Published:
Journal of Thrombosis and Thrombolysis Aims and scope Submit manuscript

Abstract

Multiple studies have shown a correlation between high on-treatment platelet reactivity (HPR) and ischemic complications after percutaneous coronary interventions (PCI); however, the role of platelet reactivity testing in order to adjust clopidogrel dose is debated. We sought to determine whether a strategy incorporating platelet reactivity testing with the Multiplate analyzer to tailor the dose of clopidogrel is superior to standard clopidogrel treatment after PCI. Between May 2008 and June 2009, 192 consecutive patients undergoing PCI were randomized to a tailored treatment strategy using the Multiplate analyzer or to uniform administration of 75 mg clopidogrel. In the tailored group, platelet function was assessed 24 h after clopidogrel loading, and patients with HPR (>46 U) received an additional 600 mg loading dose and 150 mg clopidogrel thereafter for one month. The primary endpoint was the composite of cardiac death, myocardial infarction, ischemic stroke or definite/probable stent thrombosis during six months. In the tailored group, a repeated loading dose of 600 mg clopidogrel significantly decreased platelet reactivity in patients with HPR (61.0 U [IQR: 52.5–71.5] vs. 21.5 U [15.8–30.5]; P < 0.0001) that remained unchanged during the maintenance phase on 150 mg clopidogrel (25.0 U [IQR: 19.8–27.0]; P = 0.20). The incidence of the primary endpoint was significantly higher in the standard clopidogrel group as compared to the Multiplate-tailored arm (5.3% vs. 0%, P = 0.03). In parallel, MACCE-free survival significantly improved in patients with Multiplate-tailored therapy (Kaplan–Meier log-rank: P = 0.02). Increasing the dose of clopidogrel according to the Multiplate assay may reduce ischemic complications in patients on clopidogrel after PCI.

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
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Serebruany VL, Steinhubl SR, Berger PB, Malinin AI, Bhatt DL, Topol EJ (2005) Variability in platelet responsiveness to clopidogrel among 544 individuals. J Am Coll Cardiol 45:246–251

    Article  PubMed  CAS  Google Scholar 

  2. Wiviott SD, Braunwald E, McCabe CH et al (2007) TRITON-TIMI 38 Investigators. Prasugrel versus clopidogrel in patients with acute coronary syndromes. N Engl J Med 357:2001–2015

    Article  PubMed  CAS  Google Scholar 

  3. Wallentin L, Becker RC, Budaj A et al (2009) Ticagrelor versus clopidogrel in patients with acute coronary syndromes. N Engl J Med 361:1045–1057

    Article  PubMed  CAS  Google Scholar 

  4. Aradi D, Komócsi A, Vorobcsuk A et al (2010) Prognostic significance of high on-clopidogrel platelet reactivity after percutaneous coronary intervention: systematic review and meta-analysis. Am Heart J 160:543–551

    Article  PubMed  CAS  Google Scholar 

  5. Sibbing D, Steinhubl SR, Schulz S, Schömig A, Kastrati A (2010) Platelet aggregation and its association with stent thrombosis and bleeding in clopidogrel-treated patients: initial evidence of a therapeutic window. J Am Coll Cardiol 56:317–318

    Article  PubMed  Google Scholar 

  6. Sibbing D, Schulz S, Braun S et al (2010) Antiplatelet effects of clopidogrel and bleeding in patients undergoing coronary stent placement. J Thromb Haemost 8:250–256

    Article  PubMed  CAS  Google Scholar 

  7. Price MJ, Berger PB, Teirstein PS et al (2011) GRAVITAS Investigators. 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 

  8. Aradi D, Rideg O, Vorobcsuk A, et al (2011) Justification of 150 mg clopidogrel in patients with high on-clopidogrel platelet reactivity. Eur J Clin Invest. doi:10.1111/j.1365-2362.2011.02594.x

  9. Ari H, Ozkan H, Karacinar A, Ari S, Koca V, Bozat T (2011) The EFFect of hIgh-dose ClopIdogrel treatmENT in patients with clopidogrel resistance (The EFFICIENT Trial). Int J Cardiol. doi:10.1016/j.ijcard.2010.12.083

  10. Wang XD, Zhang DF, Zhuang SW, Lai Y (2011) Modifying clopidogrel maintenance doses according to vasodilator-stimulated phosphoprotein phosphorylation index improves clinical outcome in patients with clopidogrel resistance. Clin Cardiol 34:332–338

    Article  PubMed  Google Scholar 

  11. Bonello L, Tantry US, Marcucci R et al (2010) Working Group on High On-Treatment Platelet Reactivity. Consensus and future directions on the definition of high on-treatment platelet reactivity to adenosine diphosphate. J Am Coll Cardiol 56:919–933

    Article  PubMed  CAS  Google Scholar 

  12. Bonello L, Camoin-Jau L, Arques S et al (2008) Adjusted clopidogrel loading doses according to vasodilator-stimulated phosphoprotein phosphorylation index decrease rate of major adverse cardiovascular events in patients with clopidogrel resistance: a multicenter randomized prospective study. J Am Coll Cardiol 51:1404–1411

    Article  PubMed  CAS  Google Scholar 

  13. Stone GW (2011) ADAPT-DES: a large-scale, prospective, multicenter registry examining the relationship of platelet responsiveness to stent thrombosis after DES implantation. Transcatheter Cardiovascular Therapeutics 2011, San Francisco

  14. Wijns W, Kolh P, Danchin N et al (2010) Guidelines on myocardial revascularization: the Task Force on Myocardial Revascularization of the European Society of Cardiology (ESC) and the European Association for Cardio-Thoracic Surgery (EACTS). Eur Heart J 31:2501–2555

    Article  PubMed  Google Scholar 

  15. Hamm CW, Bassand JP, Agewall S et al (2011) Eur ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation: The Task Force for the management of acute coronary syndromes (ACS) in patients presenting without persistent ST-segment elevation of the European Society of Cardiology (ESC). Eur Heart J 32:2999–3054

    Article  PubMed  Google Scholar 

  16. Trenk D et al (2011) TRIGGER-PCI: A Prospective, Randomized Trial of Prasugrel vs. Clopidogrel in Clopidogrel-Hyporesponsive Patients with Stable Ischemic Heart Disease Undergoing Percutaneous Coronary Intervention. Transcatheter Cardiovascular Therapeutics 2011, San Francisco

  17. Patti G, Grieco D, Dicuonzo G, Pasceri V, Nusca A, Di Sciascio G (2011) High versus standard clopidogrel maintenance dose after percutaneous coronary intervention and effects on platelet inhibition, endothelial function, and inflammation results of the ARMYDA-150 mg (antiplatelet therapy for reduction of myocardial damage during angioplasty) randomized study. J Am Coll Cardiol 57:771–778

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

Multiplate ADP kits were generously provided by Verum Diagnostica GmBH (Munich, Germany) for the study.

Conflicts of interest

Dr. Aradi receives consulting fees from Verum Diagnostica GmBH, Munich, Germany.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Dobri Hazarbasanov.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Hazarbasanov, D., Velchev, V., Finkov, B. et al. Tailoring clopidogrel dose according to multiple electrode aggregometry decreases the rate of ischemic complications after percutaneous coronary intervention. J Thromb Thrombolysis 34, 85–90 (2012). https://doi.org/10.1007/s11239-012-0684-z

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11239-012-0684-z

Keywords

Navigation