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Clinical Impact of Genetically Determined Platelet Reactivity

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Abstract

Dual antiplatelet therapy with aspirin and clopidogrel dramatically reduced the rate of major adverse cardiac events following percutaneous coronary intervention. Clopidogrel is a prodrug which requires a two-step hepatic biotransformation thanks to the cytochrome P450 (CYP450) enzyme system. Genetic polymorphism of CYP450 system (e.g., CYP2C19*2) responsible for altered clopidogrel metabolism is a major cause of high on-treatment platelet reactivity (HTPR), which translates into thrombotic events in stented patients. Studies demonstrated that HTPR could be overcome in poor metabolizers thanks to increased loading doses or maintenance doses of clopidogrel or with the use of more potent antiplatelet agents such as prasugrel. Other genetic polymorphisms have also been correlated with HTPR: ABCB1, ATP2B2, and TIAM2. Large-scale randomized trials with clinical endpoints remain necessary to determine the optimal antiplatelet therapy in patients carrying genetic polymorphism associated with HTPR and thrombotic events.

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Abbreviations

PCI:

Percutaneous coronary intervention

ACS:

Acute coronary syndrome

HTPR:

High on-treatment platelet reactivity

ST:

Stent thrombosis

MACE:

Major adverse cardiac events

References

  1. Sigwart, U., Puel, J., Mirkovitch, V., Joffre, F., & Kappenberger, L. (1987). Intravascular stents to prevent occlusion and restenosis after transluminal angioplasty. The New England Journal of Medicine, 316, 701–706.

    Article  PubMed  CAS  Google Scholar 

  2. de Feyter, P. J., DeScheerder, I., van den Brand, M., Laarman, G., Suryapranata, H., & Serruys, P. W. (1990). Emergency stenting for refractory acute coronary artery occlusion during coronary angioplasty. The American Journal of Cardiology, 66, 1147–1150.

    Article  PubMed  Google Scholar 

  3. Cutlip, D. E., Baim, D. S., Ho, K. K. L., Popma, J. J., Lansky, A. J., Cohen, D. J., et al. (2001). Stent thrombosis in the modern era: a pooled analysis of multicenter coronary stent clinical trials. Circulation, 103, 1967–1971.

    Article  PubMed  CAS  Google Scholar 

  4. Jakabcin, J., Spacek, R., Bystron, M., Kvasnák, M., Jager, J., Veselka, J., et al. (2010). Long-term health outcome and mortality evaluation after invasive coronary treatment using drug eluting stents with or without the IVUS guidance. Randomized control trial. HOME DES IVUS. Catheterization and Cardiovascular Interventions, 75, 578–583.

    PubMed  Google Scholar 

  5. Mehta, S., Yusuf, S., Peters, R., Bertrand, M., Lewis, B., Natarajan, M., et al. (2001). Effects of pretreatment with clopidogrel and aspirin followed by long-term therapy in patients undergoing percutaneous coronary intervention: the PCI-CURE study. The Lancet, 358, 527–533.

    Article  CAS  Google Scholar 

  6. Steinhubl, S. R., Berger, P. B., Mann, J. T., 3rd, Fry, E. T. A., DeLago, A., Wilmer, C., et al. (2002). Early and sustained dual oral antiplatelet therapy following percutaneous coronary intervention: a randomized controlled trial. Journal of the American Medical Association, 288, 2411–2420.

    Article  PubMed  CAS  Google Scholar 

  7. Sabatine, M. S., Cannon, C. P., Gibson, C. M., López-Sendón, J. L., Montalescot, G., Theroux, P., et al. (2005). Addition of clopidogrel to aspirin and fibrinolytic therapy for myocardial infarction with ST-segment elevation. The New England Journal of Medicine, 352, 1179–1189.

    Article  PubMed  CAS  Google Scholar 

  8. Yusuf, S., Zhao, F., Mehta, S. R., Chrolavicius, S., Tognoni, G., & Fox, K. K. (2001). Effects of clopidogrel in addition to aspirin in patients with acute coronary syndromes without ST-segment elevation. The New England Journal of Medicine, 345, 494–502.

    Article  PubMed  CAS  Google Scholar 

  9. Hamm, C. W., Bassand, J.-P., Agewall, S., Bax, J., Boersma, E., Bueno, H., et al. (2011). 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). European Heart Journal, 32, 2999–3054.

    Article  PubMed  Google Scholar 

  10. Wijns, W., Kolh, P., Danchin, N., Di Mario, C., Falk, V., Folliguet, T., et al. (2010). Guidelines on myocardial revascularization. European Heart Journal, 31, 2501–2555.

    Article  PubMed  Google Scholar 

  11. Kuchulakanti, P. K., Chu, W. W., Torguson, R., Ohlmann, P., Rha, S.-W., Clavijo, L. C., et al. (2006). Correlates and long-term outcomes of angiographically proven stent thrombosis with sirolimus- and paclitaxel-eluting stents. Circulation, 113, 1108–1113.

    Article  PubMed  CAS  Google Scholar 

  12. Machecourt, J., Danchin, N., Lablanche, J. M., Fauvel, J. M., Bonnet, J. L., Marliere, S., et al. (2007). Risk factors for stent thrombosis after implantation of sirolimus-eluting stents in diabetic and nondiabetic patients: the EVASTENT Matched-Cohort Registry. Journal of the American College of Cardiology, 50, 501–508.

    Article  PubMed  CAS  Google Scholar 

  13. Ong, A. T. L., Hoye, A., Aoki, J., van Mieghem, C. A. G., Rodriguez Granillo, G. A., Sonnenschein, K., et al. (2005). Thirty-day incidence and six-month clinical outcome of thrombotic stent occlusion after bare-metal, sirolimus, or paclitaxel stent implantation. Journal of the American College of Cardiology, 45, 947–953.

    Article  PubMed  CAS  Google Scholar 

  14. Barragan, P., Bouvier, J.-L., Roquebert, P.-O., Macaluso, G., Commeau, P., Comet, B., et al. (2003). Resistance to thienopyridines: clinical detection of coronary stent thrombosis by monitoring of vasodilator-stimulated phosphoprotein phosphorylation. Catheterization and Cardiovascular Interventions, 59, 295–302.

    Article  PubMed  Google Scholar 

  15. Aradi, D., Komócsi, A., Vorobcsuk, A., Rideg, O., Tokés-Füzesi, M., Magyarlaki, T., et al. (2010). Prognostic significance of high on-clopidogrel platelet reactivity after percutaneous coronary intervention: systematic review and meta-analysis. American Heart Journal, 160, 543–551.

    Article  PubMed  CAS  Google Scholar 

  16. Hulot, J.-S., Bura, A., Villard, E., Azizi, M., Remones, V., Goyenvalle, C., et al. (2006). Cytochrome P450 2C19 loss-of-function polymorphism is a major determinant of clopidogrel responsiveness in healthy subjects. Blood, 108, 2244–2247.

    Article  PubMed  CAS  Google Scholar 

  17. Kazui, M., Nishiya, Y., Ishizuka, T., Hagihara, K., Farid, N. A., Okazaki, O., et al. (2010). Identification of the human cytochrome P450 enzymes involved in the two oxidative steps in the bioactivation of clopidogrel to its pharmacologically active metabolite. Drug Metabolism and Disposition, 38, 92–99.

    Article  PubMed  CAS  Google Scholar 

  18. Pereillo, J.-M., Maftouh, M., Andrieu, A., Uzabiaga, M.-F., Fedeli, O., Savi, P., et al. (2002). Structure and stereochemistry of the active metabolite of clopidogrel. Drug Metabolism and Disposition, 30, 1288–1295.

    Article  PubMed  CAS  Google Scholar 

  19. Savi, P., Pereillo, J. M., Uzabiaga, M. F., Combalbert, J., Picard, C., Maffrand, J. P., et al. (2000). Identification and biological activity of the active metabolite of clopidogrel. Thrombosis and Haemostasis, 84, 891–896.

    PubMed  CAS  Google Scholar 

  20. Järemo, P., Lindahl, T. L., Fransson, S. G., & Richter, A. (2002). Individual variations of platelet inhibition after loading doses of clopidogrel. Journal of Internal Medicine, 252, 233–238.

    Article  PubMed  Google Scholar 

  21. Bonello, L., Tantry, U. S., Marcucci, R., Blindt, R., Angiolillo, D. J., Becker, R., et al. (2010). Consensus and future directions on the definition of high on-treatment platelet reactivity to adenosine diphosphate. Journal of the American College of Cardiology, 56, 919–933.

    Article  PubMed  CAS  Google Scholar 

  22. Bonello-Palot, N., Armero, S., Paganelli, F., Mancini, J., De Labriolle, A., Bonello, C., et al. (2009). Relation of body mass index to high on-treatment platelet reactivity and of failed clopidogrel dose adjustment according to platelet reactivity monitoring in patients undergoing percutaneous coronary intervention. The American Journal of Cardiology, 104, 1511–1515.

    Article  PubMed  CAS  Google Scholar 

  23. Silvain, J., Cayla, G., Hulot, J.-S., Finzi, J., Kerneis, M., O’Connor, S. A., Bellemain-Appaix, A., Barthélémy, O., Beygui, F., Collet, J.-P., & Montalescot, G. (2011). High on-thienopyridine platelet reactivity in elderly coronary patients: the SENIOR-PLATELET study. European Heart Journal, 33(10), 1241–1249.

    Article  PubMed  Google Scholar 

  24. Angiolillo, D. J., Fernandez-Ortiz, A., Bernardo, E., Ramírez, C., Sabaté, M., Jimenez-Quevedo, P., et al. (2005). Platelet function profiles in patients with type 2 diabetes and coronary artery disease on combined aspirin and clopidogrel treatment. Diabetes, 54, 2430–2435.

    Article  PubMed  CAS  Google Scholar 

  25. Coccheri, S. (2012). Antiplatelet therapy: controversial aspects. Thrombosis Research, 129, 225–229.

    Article  PubMed  CAS  Google Scholar 

  26. Mangiacapra, F., Patti, G., Barbato, E., Peace, A. J., Ricottini, E., Vizzi, V., et al. (2012). A therapeutic window for platelet reactivity for patients undergoing elective percutaneous coronary intervention: results of the ARMYDA-PROVE (antiplatelet therapy for reduction of myocardial damage during angioplasty–platelet reactivity for outcome validation effort) study. JACC. Cardiovascular Interventions, 5, 281–289.

    Article  PubMed  Google Scholar 

  27. Sibbing, D., Steinhubl, S. R., Schulz, S., Schömig, A., & Kastrati, A. (2010). Platelet aggregation and its association with stent thrombosis and bleeding in clopidogrel-treated patients. Journal of the American College of Cardiology, 56, 317–318.

    Article  PubMed  Google Scholar 

  28. Mega, J. L., Close, S. L., Wiviott, S. D., Shen, L., Walker, J. R., Simon, T., et al. (2010). Genetic variants in ABCB1 and CYP2C19 and cardiovascular outcomes after treatment with clopidogrel and prasugrel in the TRITON–TIMI 38 trial: a pharmacogenetic analysis. The Lancet, 376, 1312–1319.

    Article  CAS  Google Scholar 

  29. Mega, J. L., Simon, T., Collet, J.-P., Anderson, J. L., Antman, E. M., Bliden, K., et al. (2010). Reduced-function CYP2C19 genotype and risk of adverse clinical outcomes among patients treated with clopidogrel predominantly for PCI: a meta-analysis. Journal of the American Medical Association, 304, 1821–1830.

    Article  PubMed  CAS  Google Scholar 

  30. Jang, J.-S., Cho, K.-I., Jin, H.-Y., Seo, J.-S., Yang, T.-H., Kim, D.-K., et al. (2012). Meta-analysis of cytochrome P450 2C19 polymorphism and risk of adverse clinical outcomes among coronary artery disease patients of different ethnic groups treated with clopidogrel. The American Journal of Cardiology, 110, 502–508.

    Article  PubMed  CAS  Google Scholar 

  31. Umemura, K., Furuta, T., & Kondo, K. (2008). The common gene variants of CYP2C19 affect pharmacokinetics and pharmacodynamics in an active metabolite of clopidogrel in healthy subjects. Journal of Thrombosis and Haemostasis, 6, 1439–1441.

    Article  PubMed  CAS  Google Scholar 

  32. Brandt, J. T., Close, S. L., Iturria, S. J., Payne, C. D., Farid, N. A., Ernest, C. S., 2nd, et al. (2007). Common polymorphisms of CYP2C19 and CYP2C9 affect the pharmacokinetic and pharmacodynamic response to clopidogrel but not prasugrel. Journal of Thrombosis and Haemostasis, 5, 2429–2436.

    Article  PubMed  CAS  Google Scholar 

  33. Collet, J.-P., Hulot, J.-S., Pena, A., Villard, E., Esteve, J.-B., Silvain, J., et al. (2009). Cytochrome P450 2C19 polymorphism in young patients treated with clopidogrel after myocardial infarction: a cohort study. Lancet, 373, 309–317.

    Article  PubMed  CAS  Google Scholar 

  34. Postmarket Drug Safety Information for Patients and Providers—FDA Drug Safety Communication: Reduced effectiveness of Plavix (clopidogrel) in patients who are poor metabolizers of the drug [http://www.fda.gov/drugs/drugsafety/postmarketdrugsafetyinformationforpatientsandproviders/ucm203888.htm]. Accessed 20 August 2012.

  35. Lau, W. C., Gurbel, P. A., Watkins, P. B., Neer, C. J., Hopp, A. S., Carville, D. G. M., et al. (2004). Contribution of hepatic cytochrome P450 3A4 metabolic activity to the phenomenon of clopidogrel resistance. Circulation, 109, 166–171.

    Article  PubMed  CAS  Google Scholar 

  36. Mega, J. L., Close, S. L., Wiviott, S. D., Shen, L., Hockett, R. D., Brandt, J. T., et al. (2009). Cytochrome p-450 polymorphisms and response to clopidogrel. The New England Journal of Medicine, 360, 354–362.

    Article  PubMed  CAS  Google Scholar 

  37. Sibbing, D., Koch, W., Gebhard, D., Schuster, T., Braun, S., Stegherr, J., et al. (2010). Cytochrome 2C19*17 allelic variant, platelet aggregation, bleeding events, and stent thrombosis in clopidogrel-treated patients with coronary stent placement. Circulation, 121, 512–518.

    Article  PubMed  CAS  Google Scholar 

  38. Hochholzer, W., Trenk, D., Fromm, M. F., Valina, C. M., Stratz, C., Bestehorn, H.-P., et al. (2010). Impact of cytochrome P450 2C19 loss-of-function polymorphism and of major demographic characteristics on residual platelet function after loading and maintenance treatment with clopidogrel in patients undergoing elective coronary stent placement. Journal of the American College of Cardiology, 55, 2427–2434.

    Article  PubMed  CAS  Google Scholar 

  39. Shuldiner, A. R., O’Connell, J. R., Bliden, K. P., Gandhi, A., Ryan, K., Horenstein, R. B., et al. (2009). Association of cytochrome P450 2C19 genotype with the antiplatelet effect and clinical efficacy of clopidogrel therapy. Journal of the American Medical Association, 302, 849–857.

    Article  PubMed  CAS  Google Scholar 

  40. Bouman, H. J., Schömig, E., van Werkum, J. W., Velder, J., Hackeng, C. M., Hirschhäuser, C., et al. (2011). Paraoxonase-1 is a major determinant of clopidogrel efficacy. Nature Medicine, 17, 110–116.

    Article  PubMed  CAS  Google Scholar 

  41. Hulot, J.-S., Collet, J.-P., Cayla, G., Silvain, J., Allanic, F., Bellemain-Appaix, A., et al. (2011). CYP2C19 but not PON1 genetic variants influence clopidogrel pharmacokinetics, pharmacodynamics, and clinical efficacy in post-myocardial infarction patients. Circulation. Cardiovascular Interventions, 4, 422–428.

    Article  PubMed  CAS  Google Scholar 

  42. Sibbing, D., Koch, W., Massberg, S., Byrne, R. A., Mehilli, J., Schulz, S., Mayer, K., Bernlochner, I., Schömig, A., & Kastrati, A. (2011). No association of paraoxonase-1 Q192R genotypes with platelet response to clopidogrel and risk of stent thrombosis after coronary stenting. European Heart Journal, 32(13), 1605–1613.

    Article  PubMed  CAS  Google Scholar 

  43. Michelson, A. D., Furman, M. I., Goldschmidt-Clermont, P., Mascelli, M. A., Hendrix, C., Coleman, L., et al. (2000). Platelet GP IIIa Pl(A) polymorphisms display different sensitivities to agonists. Circulation, 101, 1013–1018.

    Article  PubMed  CAS  Google Scholar 

  44. Galasso, G., Santulli, G., Piscione, F., De Rosa, R., Trimarco, V., Piccolo, R., et al. (2010). The GPIIIA PlA2 polymorphism is associated with an increased risk of cardiovascular adverse events. BMC Cardiovascular Disorders, 10, 41.

    Article  PubMed  Google Scholar 

  45. Cuisset, T., Hamilos, M., Delrue, M., Frère, C., Verhamme, K., Bartunek, J., et al. (2010). Adrenergic receptor polymorphisms and platelet reactivity after treatment with dual antiplatelet therapy with aspirin and clopidogrel in acute coronary syndrome. Thrombosis and Haemostasis, 103, 774–779.

    Article  PubMed  CAS  Google Scholar 

  46. Dusse, F., Frey, U. H., Bilalic, A., Dirkmann, D., Görlinger, K., Siffert, W., et al. (2012). The GNB3 C825T polymorphism influences platelet aggregation in human whole blood. Pharmacogenetics and Genomics, 22, 43–49.

    Article  PubMed  CAS  Google Scholar 

  47. Benjafield, A. V., Jeyasingam, C. L., Nyholt, D. R., Griffiths, L. R., & Morris, B. J. (1998). G-protein beta3 subunit gene (GNB3) variant in causation of essential hypertension. Hypertension, 32, 1094–1097.

    Article  PubMed  CAS  Google Scholar 

  48. Angelillo-Scherrer, A., Fontana, P., Burnier, L., Roth, I., Sugamele, R., Brisset, A., et al. (2011). Connexin 37 limits thrombus propensity by downregulating platelet reactivity. Circulation, 124, 930–939.

    Article  PubMed  CAS  Google Scholar 

  49. Price, M. J., Carson, A. R., Murray, S. S., Phillips, T., Janel, L., Tisch, R., et al. (2012). First pharmacogenomic analysis using whole exome sequencing to identify novel genetic determinants of clopidogrel response variability: results of the Genotype Information and Functional Testing (GIFT) exome study. Journal of the American College of Cardiology, 59, E9.

    Article  Google Scholar 

  50. Simon, T., Bhatt, D. L., Bergougnan, L., Farenc, C., Pearson, K., Perrin, L., et al. (2011). Genetic polymorphisms and the impact of a higher clopidogrel dose regimen on active metabolite exposure and antiplatelet response in healthy subjects. Clinical Pharmacology and Therapeutics, 90, 287–295.

    Article  PubMed  CAS  Google Scholar 

  51. Barker, C. M., Murray, S. S., Teirstein, P. S., Kandzari, D. E., Topol, E. J., & Price, M. J. (2010). Pilot study of the antiplatelet effect of increased clopidogrel maintenance dosing and its relationship to CYP2C19 genotype in patients with high on-treatment reactivity. JACC. Cardiovascular Interventions, 3, 1001–1007.

    Article  PubMed  Google Scholar 

  52. Bonello, L., Armero, S., Ait Mokhtar, O., Mancini, J., Aldebert, P., Saut, N., et al. (2010). Clopidogrel loading dose adjustment according to platelet reactivity monitoring in patients carrying the 2C19*2 loss of function polymorphism. Journal of the American College of Cardiology, 56, 1630–1636.

    Article  PubMed  CAS  Google Scholar 

  53. Collet, J.-P., Hulot, J.-S., Anzaha, G., Pena, A., Chastre, T., Caron, C., et al. (2011). High doses of clopidogrel to overcome genetic resistance: the randomized crossover CLOVIS-2 (clopidogrel and response variability investigation study 2). JACC. Cardiovascular Interventions, 4, 392–402.

    Article  PubMed  Google Scholar 

  54. Mega, J. L. (2011). Dosing clopidogrel based on CYP2C19 genotype and the effect on platelet reactivity in patients with stable cardiovascular disease. The Journal of the American Medical Association, 306, 2221.

    Article  CAS  Google Scholar 

  55. Kim, I.-S., Jeong, Y.-H., Park, Y., Park, K.-S., Yun, S.-E., Park, J.-R., et al. (2011). Platelet inhibition by adjunctive cilostazol versus high maintenance-dose clopidogrel in patients with acute myocardial infarction according to cytochrome P450 2C19 genotype. JACC. Cardiovascular Interventions, 4, 381–391.

    Article  PubMed  Google Scholar 

  56. Wiviott, S. D., Braunwald, E., McCabe, C. H., Montalescot, G., Ruzyllo, W., Gottlieb, S., et al. (2007). Prasugrel versus clopidogrel in patients with acute coronary syndromes. The New England Journal of Medicine, 357, 2001–2015.

    Article  PubMed  CAS  Google Scholar 

  57. Serebruany, V. L. (2010). Mortality in the TRITON trial: update from the FDA prasugrel action package. The American Journal of Cardiology, 105, 1356–1357.

    Article  PubMed  Google Scholar 

  58. Wallentin, L., Becker, R. C., Budaj, A., Cannon, C. P., Emanuelsson, H., Held, C., et al. (2009). Ticagrelor versus clopidogrel in patients with acute coronary syndromes. The New England Journal of Medicine, 361, 1045–1057.

    Article  PubMed  CAS  Google Scholar 

  59. Alexopoulos, D., Dimitropoulos, G., Davlouros, P., Xanthopoulou, I., Kassimis, G., Stavrou, E. F., et al. (2011). Prasugrel overcomes high on-clopidogrel platelet reactivity post-stenting more effectively than high-dose (150-mg) clopidogrel: the importance of CYP2C19*2 genotyping. JACC. Cardiovascular Interventions, 4, 403–410.

    Article  PubMed  Google Scholar 

  60. Sardella, G., Calcagno, S., Mancone, M., Palmirotta, R., Lucisano, L., Canali, E., Stio, R. E., Pennacchi, M., Roma, A. D., Benedetti, G., Guadagni, F., Biondi-Zoccai, G., & Fedele, F. (2012). Pharmacodynamic effect of switching therapy in patients with high on-treatment platelet reactivity and genotype variation with high clopidogrel dose versus prasugrel The RESET GENE Trial. Circulation. Cardiovascular Interventions, 5(5), 698–704.

    Article  PubMed  CAS  Google Scholar 

  61. Michelson, A. D., Frelinger, A. L., 3rd, Braunwald, E., Downey, W. E., Angiolillo, D. J., Xenopoulos, N. P., et al. (2009). Pharmacodynamic assessment of platelet inhibition by prasugrel vs. clopidogrel in the TRITON-TIMI 38 trial. European Heart Journal, 30, 1753–1763.

    Article  PubMed  CAS  Google Scholar 

  62. Bliden, K. P., Tantry, U. S., Storey, R. F., Jeong, Y.-H., Gesheff, M., Wei, C., et al. (2011). The effect of ticagrelor versus clopidogrel on high on-treatment platelet reactivity: combined analysis of the ONSET/OFFSET and RESPOND studies. American Heart Journal, 162, 160–165.

    Article  PubMed  CAS  Google Scholar 

  63. Bonello, L., Pansieri, M., Mancini, J., Bonello, R., Maillard, L., Barnay, P., et al. (2011). High on-treatment platelet reactivity after prasugrel loading dose and cardiovascular events after percutaneous coronary intervention in acute coronary syndromes. Journal of the American College of Cardiology, 58, 467–473.

    Article  PubMed  CAS  Google Scholar 

  64. Wallentin, L., James, S., Storey, R. F., Armstrong, M., Barratt, B. J., Horrow, J., et al. (2010). Effect of CYP2C19 and ABCB1 single nucleotide polymorphisms on outcomes of treatment with ticagrelor versus clopidogrel for acute coronary syndromes: a genetic substudy of the PLATO trial. Lancet, 376, 1320–1328.

    Article  PubMed  CAS  Google Scholar 

  65. Tantry, U. S., Bliden, K. P., Wei, C., Storey, R. F., Armstrong, M., Butler, K., et al. (2010). First analysis of the relation between CYP2C19 genotype and pharmacodynamics in patients treated with ticagrelor versus Clopidogrel: the ONSET/OFFSET and RESPOND genotype studies. Circulation: Cardiovascular Genetics, 3, 556–566.

    Article  CAS  Google Scholar 

  66. Mega, J. L., Close, S. L., Wiviott, S. D., Shen, L., Hockett, R. D., Brandt, J. T., et al. (2009). Cytochrome P450 genetic polymorphisms and the response to prasugrel relationship to pharmacokinetic, pharmacodynamic, and clinical outcomes. Circulation, 119, 2553–2560.

    Article  PubMed  CAS  Google Scholar 

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  1. Département de Cardiologie, Centre Hospitalo-Universitaire Nord, Chemin des Bourrely, Marseille, France

    Marc Laine, Sébastien Arméro, Michaël Peyrol, Pascal Sbragia, Franck Paganelli & Laurent Bonello

  2. Département de Cardiologie, Centre Hospitalo-Universitaire de la Timone, Boulevard Jean-Moulin, Marseille, France

    Franck Thuny

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Laine, M., Arméro, S., Peyrol, M. et al. Clinical Impact of Genetically Determined Platelet Reactivity. J. of Cardiovasc. Trans. Res. 6, 398–403 (2013). https://doi.org/10.1007/s12265-012-9421-4

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