American Journal of Cardiology
Volume 102, Issue 5 , Pages 524-529 , 1 September 2008

Effectiveness of Reloading to Overcome Clopidogrel Nonresponsiveness in Patients With Acute Myocardial Infarction

  • Shlomi Matetzky, MD

      Affiliations

    • Heart Institute, Sheba Medical Center, Tel Hashomer and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
    • Corresponding Author InformationCorresponding author: Tel: +972-3-635-2303; Fax: +972-3-534-3888
  • ,
  • Paul Fefer, MD

      Affiliations

    • Heart Institute, Sheba Medical Center, Tel Hashomer and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
  • ,
  • Boris Shenkman, MD, PhD

      Affiliations

    • Hematology Institute, Sheba Medical Center, Tel Hashomer and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
  • ,
  • David Varon, MD

      Affiliations

    • Thrombosis and Hemostasis Unit, Department of Hematology, Hadassah University Hospital, Jerusalem, Israel
  • ,
  • Naphtali Savion, MD

      Affiliations

    • Goldschleger Eye Institute, Sheba Medical Center, Tel Hashomer and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
  • ,
  • Hanoch Hod, MD

      Affiliations

    • Heart Institute, Sheba Medical Center, Tel Hashomer and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel

Received 17 January 2008 ,Revised 9 April 2008 ,Accepted 9 April 2008.

References 

  1. Gurbel PA, Bliden KP, Hiatt BL, O'Connor CM. Clopidogrel for coronary stenting: response variability, drug resistance, and the effect of pretreatment platelet reactivity. Circulation. 2003;107:2908–2913
  2. Muller I, Besta F, Schulz C, Massberg S, Schonig A, Gawaz M. Prevalence of clopidogrel non-respondents among patients with stable angina pectoris scheduled for elective coronary stent placement. Thromb Haemost. 2003;89:783–787
  3. Angiolillo DJ, Fernandez-Ortiz A, Bernardo E, Ramirez C, Sabate M, Banuelos C, et al. High clopidogrel loading dose during coronary stenting: effects on drug response and interindividual variability. Eur Heart J. 2004;25:1903–1910
  4. Gurbel PA, Bliden KP, Hayes KM, Yoho JA, Herzog WR, Tantry US. The relation of dosing to clopidogrel responsiveness and the incidence of high post-treatment platelet aggregation in patients undergoing coronary stenting. J Am Coll Cardiol. 2005;45:1392–1396
  5. Serebruany VL, Steinhubl SR, Berger PB, Malinin AI, Bhatt DL, Topol EJ. Variability in platelet responsiveness to clopidogrel among 544 individuals. J Am Coll Cardiol. 2005;45:246–251
  6. Lau WC, Gurbel PA, Watkins PB, Neer CJ, Hopp AS, Carville DGM, et al. Contribution of hepatic cytochrome P450 3A4 metabolic activity to the phenomenon of clopidogrel resistance. Circulation. 2004;109:166–171
  7. Lepantalo A, Virtanen KS, Heikkila J, Wartiovaara U, Lassila R. Limited early antiplatelet effect of 300 mg clopidogrel in patients with aspirin therapy undergoing percutaneous coronary interventions. Eur Heart J. 2004;25:476–483
  8. Matetzky S, Shenkman B, Guetta V, Shechter M, Bienart R, Goldenberg I, et al. Clopidogrel resistance is associated with increased risk of recurrent atherothrombotic events in patients with acute myocardial infarction. Circulation. 2004;109:3171–3175
  9. Labarthe B, Theroux P, Angioi M, Ghitescu M. Matching the evaluation of the clinical efficacy of clopidogrel to platelet function tests relevant to the biological properties of the drug. J Am Coll Cardiol. 2005;46:638–645
  10. Cuisset T, Frere C, Quilici J, Barbou F, Morange PE, Hovasse T, et al. High post-treatment platelet reactivity identified low-responders to dual antiplatelet therapy at increased risk of recurrent cardiovascular events after stenting for acute coronary syndrome. J Thromb Haemost. 2006;4:542–549
  11. Lev EI, Patel RT, Maresh KJ, Guthikonda S, Granada J, DeLao T, et al. Aspirin and clopidogrel drug response in patients undergoing percutaneous coronary intervention: the role of dual drug resistance. J Am Coll Cardiol. 2006;47:27–33
  12. Geisler T, Langer H, Wydymus M, Göhring K, Zürn C, Bigalke B, et al. Low response to clopidogrel is associated with cardiovascular outcome after coronary stent implantation. Eur Heart J. 2006;27:2420–2425
  13. Gurbel PA, Bliden KP, Samara W, Yoho JA, Hayes K, Fissha MZ, et al. Clopidogrel effect on platelet reactivity in patients with stent thrombosis: results of the CREST Study. J Am Coll Cardiol. 2005;46:1827–1832
  14. Hochholzer W, Trenk D, Bestehorn H-P, Fischer B, Valina CM, Ferenc M, et al. Impact of the degree of peri-interventional platelet inhibition after loading with clopidogrel on early clinical outcome of elective coronary stent placement. J Am Coll Cardiol. 2006;48:1742–17450
  15. Bliden KP, DiChiara J, Tantry US, Bassi AK, Chaganti SK, Gurbel PA. Increased risk in patients with high platelet aggregation receiving chronic clopidogrel therapy undergoing percutaneous coronary intervention: is the current antiplatelet therapy adequate?. J Am Coll Cardiol. 2007;49:657–666
  16. von Beckerath N, Taubert D, Pogatsa-Murray G, Schomig E, Kastrati A, Schomig A. Absorption, metabolization, and antiplatelet effects of 300-, 600-, and 900-mg loading doses of clopidogrel: results of the ISAR-CHOICE (Intracoronary Stenting and Antithrombotic Regimen: Choose Between 3 High Oral Doses for Immediate Clopidogrel Effect) Trial. Circulation. 2005;112:2946–2950
  17. Gurbel PA, Bliden KP, Guyer K, Cho PW, Zaman KA, Kreutz RP, et al. Platelet reactivity in patients and recurrent events post-stenting: results of the PREPARE POST-STENTING Study. J Am Coll Cardiol. 2005;46:1820–1826
  18. Gurbel PA, Bliden KP, Zaman KA, Yoho JA, Hayes KM, Tantry US. Clopidogrel loading with eptifibatide to arrest the reactivity of platelets: results of the Clopidogrel Loading With Eptifibatide to Arrest the Reactivity of Platelets (CLEAR PLATELETS) Study. Circulation. 2005;111:1153–1159
  19. Montalescot G, Sideris G, Meuleman C, Bal-dit-Sollier C, Lellouche N, Steg PG, et al A randomized comparison of high clopidogrel loading doses in patients with non-ST-segment elevation acute coronary syndromes: the ALBION (Assessment of the Best Loading Dose of Clopidogrel to Blunt Platelet Activation, Inflammation and Ongoing Necrosis) trial. J Am Coll Cardiol. 2006;48:931–938
  20. Patti G, Colonna G, Pasceri V, Pepe LL, Montinaro A, Di Sciascio G. Randomized trial of high loading dose of clopidogrel for reduction of periprocedural myocardial infarction in patients undergoing coronary intervention: results from the ARMYDA-2 (Antiplatelet therapy for Reduction of MYocardial Damage during Angioplasty) Study. Circulation. 2005;111:2099–2106
  21. Kastrati A, von Beckerath N, Joost A, Pogatsa-Murray G, Gorchakova O, Schomig A. Loading with 600 mg clopidogrel in patients with coronary artery disease with and without chronic clopidogrel therapy. Circulation. 2004;110:1916–1919
  22. Samara WM, Bliden KP, Tantry US, Gurbel PA. The difference between clopidogrel responsiveness and posttreatment platelet reactivity. Thromb Res. 2005;115:89–94
  23. Varon D, Dardik R, Shenkman B, Kotev-Emeth S, Farzame N, Tamarin I, et al. A new method for quantitative analysis of whole blood platelet interaction with extracellular matrix under flow conditions. Thromb Res. 1997;85:283–294
  24. Cuisset T, Frere C, Quilici J, Morange PE, Nait-Saidi L, Carvajal J, et al. Benefit of a 600-mg loading dose of clopidogrel on platelet reactivity and clinical outcomes in patients with non-ST-segment elevation acute coronary syndrome undergoing coronary stenting. J Am Coll Cardiol. 2006;48:1339–1345
  25. Angiolillo DJ, Shoemaker S, Desai B, Yuan H, Charlton RK, Bernardo E, et al. Randomized comparison of a high clopidogrel maintenance dose in patients with diabetes mellitus and coronary artery disease: results of the Optimizing Antiplatelet Therapy in Diabetes Mellitus (OPTIMUS) Study. Circulation. 2007;115:708–716
  26. Jaremo P, Lindahl TL, Fransson SG, Richter A. Individual variations of platelet inhibition after loading doses of clopidogrel. J Intern Med. 2002;252:233–238
  27. Brandt JT, Payne CD, Wiviott SD, Weerakkody G, Farid NA, Small DS, et al. A comparison of prasugrel and clopidogrel loading doses on platelet function: magnitude of platelet inhibition is related to active metabolite formation. Am Heart J. 2007;153:66;e9–66.e16

PII: S0002-9149(08)00754-6

doi: 10.1016/j.amjcard.2008.04.028

American Journal of Cardiology
Volume 102, Issue 5 , Pages 524-529 , 1 September 2008