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Angiographic and platelet reactivity outcomes with prasugrel 60 mg pretreatment and clopidogrel 600 mg pretreatment in primary percutaneous coronary intervention

Abstract

Pretreatment with 60 mg of prasugrel is more effective than 300 mg of clopidogrel in reducing thrombotic complications with primary percutaneous coronary intervention (PCI). We compared angiographic outcomes and platelet reactivity between treatment with 60 mg of prasugrel and 600 mg of clopidogrel administered before primary PCI. In this single centre non-randomized study, 65 consecutive Asian patients with ST-elevation myocardial infarction (STEMI) received 60 mg of prasugrel before primary PCI. The pre- and post-PCI corrected thrombolysis in myocardial infarction frame count (CTFC) and the 8-h post-treatment platelet vasodilator-stimulated phosphoprotein (VASP) index was compared with a matched historical Asian STEMI cohort (n = 65) receiving 600 mg of clopidogrel pretreatment. Comparing the prasugrel and clopidogrel groups, the mean age was 54.1 ± 10.2 versus 55.5 ± 11.8 years, P = 0.238, and the mean body mass index was 24.6 ± 2.0 versus 24.7 ± 2.8 kg m−2, P = 0.393. The mean pre-PCI CTFC was 82.1 ± 30.2 versus 86.1 ± 27.6, P = 0.045, and the mean post-PCI CTFC was 21.1 ± 13.9 versus 20.1 ± 9.2, P = 0.309. Pre-PCI coronary thrombi were visualised in 6.3 versus 18.1 %, P = 0.038. The median VASP index was 22.2 ± 24.5 versus 70.5 ± 17.5 %, P < 0.001, and high on-treatment platelet reactivity (VASP index > 50 %) was observed in 13.8 versus 84.3 %, P = 0.001. Rescue intracoronary glycoprotein inhibitors were administered to 29.7 versus 51.0 %, P = 0.018, respectively. Treatment with 60 mg of prasugrel before primary PCI was associated with lower platelet reactivity, a modest trend towards better pre-PCI angiographic outcomes, less pre-PCI coronary thrombi and less rescue glycoprotein inhibitor use compared with 600 mg of clopidogrel. The very high frequency of high on-clopidogrel platelet reactivity with 600 mg of clopidogrel in this Asian STEMI cohort deserves further study.

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Abbreviations

CTFC:

Corrected thrombolysis in myocardial infarction frame count

STEMI:

ST-elevation myocardial infarction

LD:

Loading dose

PCI:

Percutaneous coronary intervention

CABG:

Coronary artery bypass grafting

TRITON–TIMI:

TRial to assess Improvement in Therapeutic Outcomes by optimizing platelet inhibitioN with prasugrel–Thrombolysis In Myocardial Infarction

VASP:

Vasodilator-stimulated phosphoprotein

MFI:

Mean fluorescent intensity

PGE1:

Prostaglandin E1

ADP:

Adenosine diphosphate

GUSTO:

Global Utilization of Streptokinase and t-PA for Occluded Coronary Arteries

SD:

Standard deviation

References

  1. 1.

    Sabatine MS, Cannon CP, Gibson CM et al (2005) Effect of clopidogrel pretreatment before percutaneous coronary intervention in patients with ST-elevation myocardial infarction treated with fibrinolytics. The PCI-CLARITY study. J Am Med Assoc 294(10):1224–1232

  2. 2.

    Hasegawa M, Sugidachi A, Ogawa T et al (2005) Stereoselective inhibition of human platelet aggregation by R-138727, the active metabolite of CS-747 (prasugrel, LY640315), a novel P2Y12 receptor inhibitor. Thromb Haemost 94:593–598

  3. 3.

    Montalescot G, Wiviott SD, Braunwald E et al (2009) Prasugrel compared with clopidogrel in patients undergoing percutaneous coronary intervention for ST-elevation myocardial infarction (TRITON–TIMI 38): double-blind, randomised controlled trial. Lancet 373:723–731

  4. 4.

    Patti G, Barczi G, Orlic D et al (2011) Outcome comparison of 600- and 300-mg loading doses of clopidogrel in patients undergoing primary percutaneous coronary intervention for ST-segment elevation myocardial infarction: results from the ARMYDA-6 MI (Antiplatelet therapy for Reduction of MYocardial Damage during Angioplasty-Myocardial Infarction) randomized study. J Am Coll Cardiol 58:1592–1599

  5. 5.

    Small DS, Payne CD, Kothare P et al (2010) Pharmacodynamics and pharmacokinetics of single doses of prasugrel 30 mg and clopidogrel 300 mg in healthy Chinese and white volunteers: an open-label trial. Clin Ther 32:365–379

  6. 6.

    van Werkum JW, van der Stelt CA, Seesing TH et al (2007) The flow cytometric VASP assay can be used to determine the effectiveness of clopidogrel in patients treated with abciximab. J Thromb Haemost 5:881–883

  7. 7.

    Gibson CM, Cannon CP, Daley WL et al (1996) TIMI frame count: a quantitative method of assessing coronary artery flow. Circulation 93:879–888

  8. 8.

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

  9. 9.

    Chan MY, Sun JL, Wang TY et al (2010) Patterns of discharge antiplatelet therapy and late outcomes among 8,582 patients with bleeding during acute coronary syndrome: a pooled analysis from PURSUIT, PARAGON-A, PARAGON-B, and SYNERGY. Am Heart J 160:1056–1064, 1064. e2

  10. 10.

    Montalescot G, Sideris G, Cohen R et al (2010) Prasugrel compared with high-dose clopidogrel in acute coronary syndrome. The randomised, double-blind ACAPULCO study. Thromb Haemost 103:213–223

  11. 11.

    Fernando H, Dart AM, Peter K et al (2011) Proton pump inhibitors, genetic polymorphisms and response to clopidogrel therapy. Thromb Haemost 105:933–944

  12. 12.

    O’Donoghue M, Antman EM, Braunwald E et al (2009) The efficacy and safety of prasugrel with and without a glycoprotein IIb/IIIa inhibitor in patients with acute coronary syndromes undergoing percutaneous intervention: a TRITON–TIMI 38 (Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition With Prasugrel-Thrombolysis In Myocardial Infarction 38) analysis. J Am Coll Cardiol 54:678–685

  13. 13.

    Wiviott SD, Trenk D, Frelinger AL et al (2007) Prasugrel compared with high loading- and maintenance-dose clopidogrel in patients with planned percutaneous coronary intervention: the Prasugrel in Comparison to Clopidogrel for Inhibition of Platelet Activation and Aggregation-Thrombolysis in Myocardial Infarction 44 trial. Circulation 116:2923–2932

  14. 14.

    Bonello L, Pansieri M, Mancini J et al (2011) High on-treatment platelet reactivity after prasugrel loading dose and cardiovascular events after percutaneous coronary intervention in acute coronary syndromes. J Am Coll Cardiol 58:467–473

  15. 15.

    Man M, Farmen M, Dumaual C et al (2010) Genetic variation in metabolizing enzyme and transporter genes: comprehensive assessment in 3 major East Asian subpopulations with comparison to Caucasians and Africans. J Clin Pharmacol 50:929–940

  16. 16.

    Chan MY, Tan K, Tan H-C et al (2012) Functional significance and differential prevalence of CYP2C19 and PON1 polymorphisms regulating clopidogrel bioactivation in Chinese, Malay and Indian subjects. Pharmacogenomics 13:533–542

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Acknowledgments

We would like to thank Dr. Richard C. Becker for his thoughtful guidance and critical review of the manuscript.

Funding

This study was supported by the Cardiovascular Research Institute, Singapore. Dr. Mark Y. Chan receives salary support from the National Medical Research Council of Singapore (NRMC/CSA/028/2010). The study drug was provided at no cost by Eli-Lilly.

Conflict of interest

Dr. Mark Y. Chan and Matthew T. Roe have received research funding, speaker’s fees and honoraria from Eli-Lilly (Indianapolis, IN). Dr. Adrian Low has received honoraria from Eli-Lilly (Singapore, Singapore). Dr. Mark Y. Chan and Adrian Low have received honoraria from Astra-Zeneca (Singapore, Singapore). Dr. Swee-Guan Teo has received speaker’s fees from Astra-Zeneca (Singapore, Singapore). All other authors do not have any conflict of interests to declare.

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Correspondence to Mark Y. Chan.

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Li, Y., Tai, B., Sia, W. et al. Angiographic and platelet reactivity outcomes with prasugrel 60 mg pretreatment and clopidogrel 600 mg pretreatment in primary percutaneous coronary intervention. J Thromb Thrombolysis 34, 499–505 (2012). https://doi.org/10.1007/s11239-012-0782-y

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Keywords

  • Acute myocardial infarction
  • Percutaneous coronary intervention
  • Platelet reactivity
  • Thienopyridine