American Heart Journal
Volume 157, Issue 3 , Pages 562.e1-562.e9 , March 2009

Assessment of P2Y12 inhibition with the point-of-care device VerifyNow P2Y12 in patients treated with prasugrel or clopidogrel coadministered with aspirin

  • Christoph Varenhorst, MD

      Affiliations

    • Uppsala Clinical Research Center and Department Medical Sciences and Cardiology, Uppsala University, Sweden
    • Corresponding Author InformationReprint requests: Christoph Varenhorst, MD, Uppsala Clinical Research Center and Department Medical Sciences, Uppsala University Hospital, 751 85 Uppsala, Sweden.
  • ,
  • Stefan James, MD, PhD

      Affiliations

    • Uppsala Clinical Research Center and Department Medical Sciences and Cardiology, Uppsala University, Sweden
  • ,
  • David Erlinge, MD, PhD

      Affiliations

    • Department of Cardiology, Lund University, Lund, Sweden
  • ,
  • Oscar Ö. Braun, MD, PhD

      Affiliations

    • Department of Cardiology, Lund University, Lund, Sweden
  • ,
  • John T. Brandt, MD

      Affiliations

    • Eli Lilly and Company, Indianapolis, IN
  • ,
  • Kenneth J. Winters, MD

      Affiliations

    • Eli Lilly and Company, Indianapolis, IN
  • ,
  • Joseph A. Jakubowski, PhD

      Affiliations

    • Eli Lilly and Company, Indianapolis, IN
  • ,
  • Sylvia Olofsson, MSci

      Affiliations

    • Uppsala Clinical Research Center and Department Medical Sciences and Cardiology, Uppsala University, Sweden
  • ,
  • Lars Wallentin, MD, PhD

      Affiliations

    • Uppsala Clinical Research Center and Department Medical Sciences and Cardiology, Uppsala University, Sweden
  • ,
  • Agneta Siegbahn, MD, PhD

      Affiliations

    • Coagulation Laboratory, Department Medical Sciences, Uppsala, Sweden

Received 20 May 2008 ,Accepted 26 November 2008.

References 

  1. Bertrand ME, Rupprecht HJ, Urban P, et al. Double-blind study of the safety of clopidogrel with and without a loading dose in combination with aspirin compared with ticlopidine in combination with aspirin after coronary stenting: the clopidogrel aspirin stent international cooperative study (CLASSICS). Circulation. 2000;102:624–629
  2. Anderson JL, Adams CD, Antman EM, et al. ACC/AHA 2007 guidelines for the management of patients with unstable angina/non–ST-elevation myocardial infarction: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 2002 Guidelines for the Management of Patients With Unstable Angina/Non–ST-Elevation Myocardial Infarction) developed in collaboration with the American College of Emergency Physicians, the Society for Cardiovascular Angiography and Interventions, and the Society of Thoracic Surgeons endorsed by the American Association of Cardiovascular and Pulmonary Rehabilitation and the Society for Academic Emergency Medicine. J Am Coll Cardiol. 2007;50:e1–e157
  3. Task Force for Diagnosis and Treatment of Non-ST-Segment Elevation Acute Coronary Syndromes of European Society of Cardiology , Bassand JP, Hamm CW, et al. Guidelines for the diagnosis and treatment of non–ST-segment elevation acute coronary syndromes. Eur Heart J. 2007;28:1598–1660
  4. Gurbel PA, Tantry US. Clopidogrel resistance?. Thromb Res. 2007;120:311–321
  5. Hochholzer W, Trenk D, Bestehorn HP, 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;48:1742–1750
  6. Matetzky S, Shenkman B, Guetta V, et al. Clopidogrel resistance is associated with increased risk of recurrent atherothrombotic events in patients with acute myocardial infarction. Circulation. 2004;109:3171–3175
  7. Gurbel PA, Bliden KP, Guyer K, 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
  8. Cuisset T, Frere C, Quilici 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
  9. Müller I, Besta F, Schulz C, et al. Prevalence of clopidogrel non-responders among patients with stable angina pectoris scheduled for elective coronary stent placement. Thromb Haemost. 2003;89:783–787
  10. Buonamici P, Marcucci R, Migliorini A, et al. Impact of platelet reactivity after clopidogrel administration on drug-eluting stent thrombosis. J Am Coll Cardiol. 2007;49:2312–2317
  11. Jakubowski JA, Winters KJ, Naganuma H, et al. Prasugrel: a novel thienopyridine antiplatelet agent. A review of preclinical and clinical studies and the mechanistic basis for its distinct antiplatelet profile. Cardiovasc Drug Rev. 2007;25:357–374
  12. Niitsu Y, Jakubowski JA, Sugidachi A, et al. Pharmacology of CS-747 (prasugrel, LY640315), a novel, potent antiplatelet agent with in vivo P2Y12 receptor antagonist activity. Semin Thromb Hemost. 2005;31:184–194
  13. Wallentin L, Varenhorst C, James S, et al. Prasugrel achieves greater and faster P2Y12receptor-mediated platelet inhibition than clopidogrel due to more efficient generation of its active metabolite in aspirin-treated patients with coronary artery disease. Eur Heart J. 2008;29:21–30
  14. Wiviott SD, Braunwald E, McCabe CH, et al. Prasugrel versus clopidogrel in patients with acute coronary syndromes. N Engl J Med. 2007;357:2001–2015
  15. Michelson AD, Frelinger AL, Furman MI. Current options in platelet function testing. Am J Cardiol. 2006;98:4N–10N
  16. Smith JW, Steinhubl SR, Lincoff AM, et al. Rapid platelet-function assay: an automated and quantitative cartridge-based method. Circulation. 1999;99:620–625
  17. Aleil B, Ravanat C, Cazenave JP, et al. Flow cytometric analysis of intraplatelet VASP phosphorylation for the detection of clopidogrel resistance in patients with ischemic cardiovascular diseases. J Thromb Haemost. 2005;3:85–92
  18. Small DS, Farid NA, Payne CD, et al. Prasugrel 60 mg and clopidogrel 300 mg loading doses: a pharmacokinetic basis for the observed difference in platelet aggregation response. Am J Cardiol. 2006;98:200M
  19. Landis JR, Koch GG. The measurement of observer agreement for categorical data. Biometrics. 1977;33:159–174
  20. Brandt JT, Payne CD, Wiviott SD, 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
  21. Jernberg T, Payne CD, Winters KJ, et al. Prasugrel achieves greater inhibition of platelet aggregation and a lower rate of non-responders compared with clopidogrel in aspirin-treated patients with stable coronary artery disease. [see comment] Eur Heart J. 2006;27:1166–1173
  22. Jakubowski JA, Matsushima N, Asai F, et al. A multiple dose study of prasugrel (CS-747), a novel thienopyridine P2Y12 inhibitor, compared with clopidogrel in healthy humans. Br J Clin Pharmacol. 2007;63:421–430
  23. Payne CD, Li YG, Small DS, et al. Increased active metabolite formation explains the greater platelet inhibition with prasugrel compared to high-dose clopidogrel. J Cardiovasc Pharmacol. 2007;50:555–562
  24. Storey RF, Newby LJ, Heptinstall S. Effects of P2Y(1) and P2Y(12) receptor antagonists on platelet aggregation induced by different agonists in human whole blood. Platelets. 2001;12:443–447
  25. Michelson AD. Platelet function testing in cardiovascular diseases. Circulation. 2004;110:e489–e493
  26. Paniccia R, Antonucci E, Gori AM, et al. Different methodologies for evaluating the effect of clopidogrel on platelet function in. J Thromb Haemost. 2007;5:1839–1847
  27. van Werkum JW, van Der Stelt CA, Seesing TH, et al. A head-to-head comparison between the VerifyNow P2Y12 assay and light transmittance aggregometry for monitoring the individual platelet response to clopidogrel in patients undergoing elective percutaneous coronary intervention. J Thromb Haemost. 2006;4:2516–2518
  28. von Beckerath N, Pogatsa-Murray G, Wieczorek A, et al. Correlation of a new point-of-care test with conventional optical aggregometry for the assessment of clopidogrel responsiveness. Thromb Haemost. 2006;95:910–911
  29. Jakubowski JA, Payne CD, Li YG, et al. The use of the VerifyNow P2Y12 point-of-care device to monitor platelet function across a range of P2Y12 inhibition levels following prasugrel and clopidogrel administration. Thromb Haemost. 2008;99:409–415
  30. Husted S, Emanuelsson H, Heptinstall S, et al. 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. 2006;27:1038–1047
  31. Bonello L, Camoin-Jau L, Arques S, et al. 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. 2008;51:1404–1411
  32. Gurbel PA, Bliden KP, Hiatt BL, et al. Clopidogrel for coronary stenting: response variability, drug resistance, and the effect of pretreatment platelet reactivity. Circulation. 2003;107:2908–2913
  33. Gurbel PA, Bliden KP, Zaman KA, et al. 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
  34. Cuisset T, Frere C, Quilici J, et al. High post-treatment platelet reactivity is associated with a high incidence of myonecrosis after stenting for non-ST elevation acute coronary syndromes. Thromb Haemost. 2007;97:282–287
  35. Barragan P, Bouvier JL, Roquebert PO, et al. Resistance to thienopyridines: clinical detection of coronary stent thrombosis by monitoring of vasodilator-stimulated phosphoprotein phosphorylation. Catheter Cardiovasc Interv. 2003;59:295–302
  36. Price MJ, Endemann S, Gollapudi RR, et al. Prognostic significance of post-clopidogrel platelet reactivity assessed by a point-of-care assay on thrombotic events after drug-eluting stent implantation. Eur Heart J. 2008;29:992–1000
  37. Wiviott SD, Antman EM, Gibson CM, et al. Evaluation of prasugrel compared with clopidogrel in patients with acute coronary syndromes: design and rationale for the TRial to assess Improvement in Therapeutic Outcomes by optimizing platelet InhibitioN with prasugrel Thrombolysis In Myocardial Infarction 38 (TRITON-TIMI 38). Am Heart J. 2006;152:627–635
  38. Yusuf S, Zhao F, Mehta SR, et al. Effects of clopidogrel in addition to aspirin in patients with acute coronary syndromes without ST-segment elevation. N Engl J Med. 2001;345:494–502
  39. Price MJ, Coleman JL, Steinhubl SR, et al. Onset and offset of platelet inhibition after high-dose clopidogrel loading and standard daily therapy measured by a point-of-care assay in healthy volunteers. Am J Cardiol. 2006;98:681–684
  40. Chen L, Bracey AW, Radovancevic R, et al. Clopidogrel and bleeding in patients undergoing elective coronary artery bypass grafting. J Thorac Cardiovasc Surg. 2004;128:425–431

PII: S0002-8703(08)01044-2

doi: 10.1016/j.ahj.2008.11.021

American Heart Journal
Volume 157, Issue 3 , Pages 562.e1-562.e9 , March 2009