Role of genetic testing in patients undergoing percutaneous coronary intervention

Expert Review of Clinical Pharmacology

Volumn 11, Issue 2, 2018, Pages 151-164

  Moon, Jae Youn ^a   Franchi, Francesco ^a   Rollini, Fabiana ^a   Rivas Rios, Jose R ^a   Kureti, Megha ^a   Cavallari, Larisa H ^b,c   Angiolillo, Dominick J ^a  

^a UNIVERSITY OF FLORIDA COLLEGE OF MEDICINE   (United States)

^b UNIVERSITY OF FLORIDA HEALTH   (United States)

^c UNIVERSITY OF FLORIDA   (United States)

Author keywords

Clopidogrel; CYP2C19; genotype; P2Y12 receptor antagonist; pharmacogenomics

Indexed keywords

CLOPIDOGREL; CYTOCHROME P450 2C19; PRASUGREL; PURINERGIC P2Y RECEPTOR ANTAGONIST; PURINERGIC P2Y12 RECEPTOR; TICAGRELOR; ADENOSINE; ANTITHROMBOCYTIC AGENT; CYP2C19 PROTEIN, HUMAN; TICLOPIDINE;

ALLELE; CARDIAC PATIENT; CLINICAL OUTCOME; DUAL ANTIPLATELET THERAPY; GENETIC SCREENING; GENOTYPE; HEREDITY; HUMAN; META ANALYSIS (TOPIC); PERCUTANEOUS CORONARY INTERVENTION; PERSONALIZED MEDICINE; PRACTICE GUIDELINE; RANDOMIZED CONTROLLED TRIAL (TOPIC); REVIEW; ANALOGS AND DERIVATIVES; GENETICS; PROCEDURES;

ADENOSINE; CYTOCHROME P-450 CYP2C19; GENETIC TESTING; HUMANS; PERCUTANEOUS CORONARY INTERVENTION; PLATELET AGGREGATION INHIBITORS; PRASUGREL HYDROCHLORIDE; PRECISION MEDICINE; PURINERGIC P2Y RECEPTOR ANTAGONISTS; TICLOPIDINE;

EID: 85041238857     PISSN: 17512433     EISSN: 17512441     Source Type: Journal    
DOI: 10.1080/17512433.2017.1353909     Document Type: Review

References (127)

1. Angiolillo DJ., The evolution of antiplatelet therapy in the treatment of acute coronary syndromes: from aspirin to the present day. Drugs. 2012;72(16):2087–2116.
2. Levine GN, Bates ER, Bittl JA, et al. 2016 ACC/AHA guideline focused update on duration of dual antiplatelet therapy in patients with coronary artery disease: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol. 2016;68(10):1082–1115.
3. Franchi F, Angiolillo DJ., Novel antiplatelet agents in acute coronary syndrome. Nat Rev Cardiol. 2015;12(1):30–47.
4. Franchi F, Rollini F, Angiolillo DJ. Antithrombotic therapy for patients with STEMI undergoing primary PCI. Nat Rev Cardiol. 2017;14(6):361–379.
5. Sherwood MW, Wiviott SD, Peng SA, et al. Early clopidogrel versus prasugrel use among contemporary STEMI and NSTEMI patients in the US: insights from the National Cardiovascular Data Registry. J Am Heart Assoc. 2014;3(2):e000849.
6. Fan W, Plent S, Prats J, et al. Trends in P2Y12 inhibitor use in patients referred for invasive evaluation of coronary artery disease in contemporary US practice. Am J Cardiol. 2016;117(9):1439–1443.
7. Angiolillo DJ, Fernandez-Ortiz A, Bernardo E, et al. Variability in individual responsiveness to clopidogrel: clinical implications, management, and future perspectives. J Am Coll Cardiol. 2007;49(14):1505–1516.
8. Tantry US, Bonello L, Aradi D, et al. Consensus and update on the definition of on-treatment platelet reactivity to adenosine diphosphate associated with ischemia and bleeding. J Am Coll Cardiol. 2013;62(24):2261–2273.
9. Rollini F, Tello-Montoliu A, Angiolillo DJ. Advances in platelet function testing assessing bleeding complications in patients with coronary artery disease. Platelets. 2012;23(7):537–551.
10. Shuldiner AR, O’Connell JR, Bliden KP, et al. Association of cytochrome P450 2C19 genotype with the antiplatelet effect and clinical efficacy of clopidogrel therapy. JAMA. 2009;302(8):849–857.
11. Simon T, Verstuyft C, Mary-Krause M, et al. Genetic determinants of response to clopidogrel and cardiovascular events. N Engl J Med. 2009;360(4):363–375.
12. Mega JL, Simon T, Collet JP, et al. Reduced-function CYP2C19 genotype and risk of adverse clinical outcomes among patients treated with clopidogrel predominantly for PCI: a meta-analysis. JAMA. 2010;304(16):1821–1830.
13. Cavallari LH, Obeng AO. Genetic determinants of P2Y12 inhibitors and clinical implications. Interv Cardiol Clin. 2017;6(1):141–149.
14. Roberts JD, Wells GA, Le May MR, et al. Point-of-care genetic testing for personalisation of antiplatelet treatment (RAPID GENE): a prospective, randomised, proof-of-concept trial. Lancet. 2012;379(9827):1705–1711.
15. Trenk D, Hochholzer W. Genetics of platelet inhibitor treatment. Br J Clin Pharmacol. 2014;77(4):642–653.
16. Savi P, Pereillo JM, Uzabiaga MF, et al. Identification and biological activity of the active metabolite of clopidogrel. Thromb Haemost. 2000;84(5):891–896.
17. Steinhubl SR, Berger PB, Mann JT, 3rd, et al. Early and sustained dual oral antiplatelet therapy following percutaneous coronary intervention: a randomized controlled trial. JAMA. 2002;288(19):2411–2420.
18. Chen ZM, Jiang LX, Chen YP, et al. Addition of clopidogrel to aspirin in 45,852 patients with acute myocardial infarction: randomised placebo-controlled trial. Lancet. 2005;366(9497):1607–1621.
19. Sabatine MS, Cannon CP, Gibson CM, et al. Addition of clopidogrel to aspirin and fibrinolytic therapy for myocardial infarction with ST-segment elevation. N Engl J Med. 2005;352(12):1179–1189.
20. 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(7):494–502.
21. 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(4):357–374.
22. Rehmel JL, Eckstein JA, Farid NA, et al. Interactions of two major metabolites of prasugrel, a thienopyridine antiplatelet agent, with the cytochromes P450. Drug Metab Dispos. 2006;34(4):600–607.
23. Wiviott SD, Trenk D, Frelinger AL, et al. 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. 2007;116(25):2923–2932.
24. Price MJ, Walder JS, Baker BA, et al. Recovery of platelet function after discontinuation of prasugrel or clopidogrel maintenance dosing in aspirin-treated patients with stable coronary disease: the recovery trial. J Am Coll Cardiol. 2012;59(25):2338–2343.
25. Wiviott SD, Braunwald E, McCabe CH, et al. Prasugrel versus clopidogrel in patients with acute coronary syndromes. N Engl J Med. 2007;357(20):2001–2015.
26. Erlinge D, Ten BJ, Foley D, et al. Reduction in platelet reactivity with prasugrel 5 mg in low-body-weight patients is noninferior to prasugrel 10 mg in higher-body-weight patients: results from the FEATHER trial. J Am Coll Cardiol. 2012;60(20):2032–2040.
27. Erlinge D, Gurbel PA, James S, et al. Prasugrel 5 mg in the very elderly attenuates platelet inhibition but maintains noninferiority to prasugrel 10 mg in nonelderly patients: the GENERATIONS trial, a pharmacodynamic and pharmacokinetic study in stable coronary artery disease patients. J Am Coll Cardiol. 2013;62(7):577–583.
28. Ferreiro JL, Angiolillo DJ. New directions in antiplatelet therapy. Circ Cardiovasc Interv. 2012;5(3):433–445.
29. Franchi F, Rollini F, Park Y, et al. Novel antiplatelet agents: the current state and what is coming down the pike. Prog Cardiovasc Dis. 2015;58(3):267–277.
30. Capodanno D, Dharmashankar K, Angiolillo DJ. Mechanism of action and clinical development of ticagrelor, a novel platelet ADP P2Y12 receptor antagonist. Expert Rev Cardiovasc Ther. 2010;8(2):151–158.
31. Teng R, Oliver S, Hayes MA, et al. Absorption, distribution, metabolism, and excretion of ticagrelor in healthy subjects. Drug Metab Dispos. 2010;38(9):1514–1521.
32. Vang JJ, Nilsson L, Berntsson P, et al. Ticagrelor binds to human P2Y(12) independently from ADP but antagonizes ADP-induced receptor signaling and platelet aggregation. J Thromb Haemost. 2009;7(9):1556–1565.
33. Gurbel PA, Bliden KP, Butler K, et al. Randomized double-blind assessment of the ONSET and OFFSET of the antiplatelet effects of ticagrelor versus clopidogrel in patients with stable coronary artery disease: the ONSET/OFFSET study. Circulation. 2009;120(25):2577–2585.
34. Wallentin L, Becker RC, Budaj A, et al. Ticagrelor versus clopidogrel in patients with acute coronary syndromes. N Engl J Med. 2009;361(11):1045–1057.
35. Armstrong D, Summers C, Ewart L, et al. Characterization of the adenosine pharmacology of ticagrelor reveals therapeutically relevant inhibition of equilibrative nucleoside transporter 1. J Cardiovasc Pharmacol Ther. 2014;19(2):209–219.
36. Cattaneo M, Schulz R, Nylander S. Adenosine-mediated effects of ticagrelor: evidence and potential clinical relevance. J Am Coll Cardiol. 2014;63(23):2503–2509.
37. Marin F, Gonzalez-Conejero R, Capranzano P, et al. Pharmacogenetics in cardiovascular antithrombotic therapy. J Am Coll Cardiol. 2009;54(12):1041–1057.
38. Roses AD. Pharmacogenetics and future drug development and delivery. Lancet. 2000;355(9212):1358–1361.
39. Cavallari LH, Weitzel KW, Elsey AR, et al. Institutional profile: University of Florida Health Personalized Medicine Program. Pharmacogenomics. 2017;18(5):421–426.
40. Bates ER, Lau WC, Angiolillo DJ. Clopidogrel-drug interactions. J Am Coll Cardiol. 2011;57(11):1251–1263.
41. Scott SA, Sangkuhl K, Shuldiner AR, et al. PharmGKB summary: very important pharmacogene information for cytochrome P450, family 2, subfamily C, polypeptide 19. Pharmacogenet Genomics. 2012;22(2):159–165.
42. Trenk D, Hochholzer W, Fromm MF, et al. Cytochrome P450 2C19 681G>A polymorphism and high on-clopidogrel platelet reactivity associated with adverse 1-year clinical outcome of elective percutaneous coronary intervention with drug-eluting or bare-metal stents. J Am Coll Cardiol. 2008;51(20):1925–1934.
43. Sibbing D, Stegherr J, Latz W, et al. Cytochrome P450 2C19 loss-of-function polymorphism and stent thrombosis following percutaneous coronary intervention. Eur Heart J. 2009;30(8):916–922.
44. Collet JP, Hulot JS, Pena A, et al. Cytochrome P450 2C19 polymorphism in young patients treated with clopidogrel after myocardial infarction: a cohort study. Lancet. 2009;373(9660):309–317.
45. Hulot JS, Bura A, Villard E, et al. Cytochrome P450 2C19 loss-of-function polymorphism is a major determinant of clopidogrel responsiveness in healthy subjects. Blood. 2006;108(7):2244–2247.
46. Mega JL, Close SL, Wiviott SD, et al. Cytochrome p-450 polymorphisms and response to clopidogrel. N Engl J Med. 2009;360(4):354–362.
47. Scott SA, Sangkuhl K, Stein CM, et al. Clinical Pharmacogenetics Implementation Consortium guidelines for CYP2C19 genotype and clopidogrel therapy: 2013 update. Clin Pharmacol Ther. 2013;94(3):317–323.
48. Man M, Farmen M, Dumaual C, et al. 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. 2010;50(8):929–940.
49. Holmes DR, Jr., Dehmer GJ, Kaul S, et al. ACCF/AHA clopidogrel clinical alert: approaches to the FDA “boxed warning”: a report of the American College of Cardiology Foundation Task Force on clinical expert consensus documents and the American Heart Association endorsed by the Society for Cardiovascular Angiography and Interventions and the Society of Thoracic Surgeons. J Am Coll Cardiol. 2010;56(4):321–341.
50. Jeong YH, Abadilla KA, Tantry US, et al. Influence of CYP2C19*2 and *3 loss-of-function alleles on the pharmacodynamic effects of standard- and high-dose clopidogrel in East Asians undergoing percutaneous coronary intervention: the results of the ACCEL-DOUBLE-2N3 study. J Thromb Haemost. 2013;11(6):1194–1197.
51. Frere C, Cuisset T, Gaborit B, et al. The CYP2C19*17 allele is associated with better platelet response to clopidogrel in patients admitted for non-ST acute coronary syndrome. J Thromb Haemost. 2009;7(8):1409–1411.
52. Sibbing D, Koch W, Gebhard D, et al. Cytochrome 2C19*17 allelic variant, platelet aggregation, bleeding events, and stent thrombosis in clopidogrel-treated patients with coronary stent placement. Circulation. 2010;121(4):512–518.
53. Caudle KE, Dunnenberger HM, Freimuth RR, et al. Standardizing terms for clinical pharmacogenetic test results: consensus terms from the Clinical Pharmacogenetics Implementation Consortium (CPIC). Genet Med. 2017;19(2):215–223.
54. Jeong YH, Tantry US, Kim IS, et al. Effect of CYP2C19*2 and *3 loss-of-function alleles on platelet reactivity and adverse clinical events in East Asian acute myocardial infarction survivors treated with clopidogrel and aspirin. Circ Cardiovasc Interv. 2011;4(6):585–594.
55. Simon T, Bhatt DL, Bergougnan L, et al. Genetic polymorphisms and the impact of a higher clopidogrel dose regimen on active metabolite exposure and antiplatelet response in healthy subjects. Clin Pharmacol Ther. 2011;90(2):287–295.
56. Brandt JT, Close SL, Iturria SJ, et al. Common polymorphisms of CYP2C19 and CYP2C9 affect the pharmacokinetic and pharmacodynamic response to clopidogrel but not prasugrel. J Thromb Haemost. 2007;5(12):2429–2436.
57. Li Y, Tang HL, Hu YF, et al. The gain-of-function variant allele CYP2C19*17: a double-edged sword between thrombosis and bleeding in clopidogrel-treated patients. J Thromb Haemost. 2012;10(2):199–206.
58. Holmes MV, Perel P, Shah T, et al. CYP2C19 genotype, clopidogrel metabolism, platelet function, and cardiovascular events: a systematic review and meta-analysis. JAMA. 2011;306(24):2704–2714.
59. Shuldiner AR, Vesely MR, Fisch A. CYP2C19 genotype and cardiovascular events. JAMA. 2012;307(14):1482; author reply 1484-1485.
60. Mega JL, Topol EJ, Sabatine MS. CYP2C19 genotype and cardiovascular events. JAMA. 2012;307(14):1482-1483; author reply 1484-1485.
61. Siller-Matula JM, Trenk D, Schror K, et al. How to improve the concept of individualised antiplatelet therapy with P2Y12 receptor inhibitors–is an algorithm the answer? Thromb Haemost. 2015;113(1):37–52.
62. Wallentin L, James S, Storey RF, et al. 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. 2010;376(9749):1320–1328.
63. Pare G, Mehta SR, Yusuf S, et al. Effects of CYP2C19 genotype on outcomes of clopidogrel treatment. N Engl J Med. 2010;363(18):1704–1714.
64. Sorich MJ, Rowland A, McKinnon RA, et al. CYP2C19 genotype has a greater effect on adverse cardiovascular outcomes following percutaneous coronary intervention and in Asian populations treated with clopidogrel: a meta-analysis. Circ Cardiovasc Genet. 2014;7(6):895–902.
65. Tiroch KA, Sibbing D, Koch W, et al. Protective effect of the CYP2C19 *17 polymorphism with increased activation of clopidogrel on cardiovascular events. Am Heart J. 2010;160(3):506–512.
66. Sibbing D, Gebhard D, Koch W, et al. Isolated and interactive impact of common CYP2C19 genetic variants on the antiplatelet effect of chronic clopidogrel therapy. J Thromb Haemost. 2010;8(8):1685–1693.
67. Kelly RP, Close SL, Farid NA, et al. Pharmacokinetics and pharmacodynamics following maintenance doses of prasugrel and clopidogrel in Chinese carriers of CYP2C19 variants. Br J Clin Pharmacol. 2012;73(1):93–105.
68. Gurbel PA, Bergmeijer TO, Tantry US, et al. The effect of CYP2C19 gene polymorphisms on the pharmacokinetics and pharmacodynamics of prasugrel 5-mg, prasugrel 10-mg and clopidogrel 75-mg in patients with coronary artery disease. Thromb Haemost. 2014;112(3):589–597.
69. Braun OO, Angiolillo DJ, Ferreiro JL, et al. Enhanced active metabolite generation and platelet inhibition with prasugrel compared to clopidogrel regardless of genotype in thienopyridine metabolic pathways. Thromb Haemost. 2013;110(6):1223–1231.
70. Mega JL, Close SL, Wiviott SD, et al. Cytochrome P450 genetic polymorphisms and the response to prasugrel: relationship to pharmacokinetic, pharmacodynamic, and clinical outcomes. Circulation. 2009;119(19):2553–2560.
71. Mega JL, Close SL, Wiviott SD, et al. Genetic variants in ABCB1 and CYP2C19 and cardiovascular outcomes after treatment with clopidogrel and prasugrel in the TRITON-TIMI 38 trial: a pharmacogenetic analysis. Lancet. 2010;376(9749):1312–1319.
72. Tantry US, Bliden KP, Wei C, et al. First analysis of the relation between CYP2C19 genotype and pharmacodynamics in patients treated with ticagrelor versus clopidogrel: the ONSET/OFFSET and RESPOND genotype studies. Circ Cardiovasc Genet. 2010;3(6):556–566.
73. Varenhorst C, Eriksson N, Johansson A, et al. Effect of genetic variations on ticagrelor plasma levels and clinical outcomes. Eur Heart J. 2015;36(29):1901–1912.
74. Lewis JP, Horenstein RB, Ryan K, et al. The functional G143E variant of carboxylesterase 1 is associated with increased clopidogrel active metabolite levels and greater clopidogrel response. Pharmacogenet Genomics. 2013;23(1):1–8.
75. Harmsze A, Van Werkum JW, Bouman HJ, et al. Besides CYP2C19*2, the variant allele CYP2C9*3 is associated with higher on-clopidogrel platelet reactivity in patients on dual antiplatelet therapy undergoing elective coronary stent implantation. Pharmacogenet Genomics. 2010;20(1):18–25.
76. Malek LA, Kisiel B, Spiewak M, et al. Coexisting polymorphisms of P2Y12 and CYP2C19 genes as a risk factor for persistent platelet activation with clopidogrel. Circ J. 2008;72(7):1165–1169.
77. Bouman HJ, Schomig E, van Werkum JW, et al. Paraoxonase-1 is a major determinant of clopidogrel efficacy. Nat Med. 2011;17(1):110–116.
78. Angiolillo DJ, Fernandez-Ortiz A, Bernardo E, et al. PlA polymorphism and platelet reactivity following clopidogrel loading dose in patients undergoing coronary stent implantation. Blood Coagul Fibrinolysis. 2004;15(1):89–93.
79. Angiolillo DJ, Fernandez-Ortiz A, Bernardo E, et al. Contribution of gene sequence variations of the hepatic cytochrome P450 3A4 enzyme to variability in individual responsiveness to clopidogrel. Arterioscler Thromb Vasc Biol. 2006;26(8):1895–1900.
80. Tang M, Mukundan M, Yang J, et al. Antiplatelet agents aspirin and clopidogrel are hydrolyzed by distinct carboxylesterases, and clopidogrel is transesterificated in the presence of ethyl alcohol. J Pharmacol Exp Ther. 2006;319(3):1467–1476.
81. Zhu HJ, Wang X, Gawronski BE, et al. Carboxylesterase 1 as a determinant of clopidogrel metabolism and activation. J Pharmacol Exp Ther. 2013;344(3):665–672.
82. Cayla G, Hulot JS, O’Connor SA, et al. Clinical, angiographic, and genetic factors associated with early coronary stent thrombosis. JAMA. 2011;306(16):1765–1774.
83. Hulot JS, Collet JP, Cayla G, et al. CYP2C19 but not PON1 genetic variants influence clopidogrel pharmacokinetics, pharmacodynamics, and clinical efficacy in post-myocardial infarction patients. Circ Cardiovasc Interv. 2011;4(5):422–428.
84. Sibbing D, Koch W, Massberg S, et al. No association of paraoxonase-1 Q192R genotypes with platelet response to clopidogrel and risk of stent thrombosis after coronary stenting. Eur Heart J. 2011;32(13):1605–1613.
85. Trenk D, Hochholzer W, Fromm MF, et al. Paraoxonase-1 Q192R polymorphism and antiplatelet effects of clopidogrel in patients undergoing elective coronary stent placement. Circ Cardiovasc Genet. 2011;4(4):429–436.
86. Jaitner J, Morath T, Byrne RA, et al. No association of ABCB1 C3435T genotype with clopidogrel response or risk of stent thrombosis in patients undergoing coronary stenting. Circ Cardiovasc Interv. 2012;5(1):82-88, S81-S82.
87. Floyd CN, Ferro A. The PlA1/A2 polymorphism of glycoprotein IIIa in relation to efficacy of antiplatelet drugs: a systematic review and meta-analysis. Br J Clin Pharmacol. 2014;77(3):446–457.
88. US Food and Drug Administration. Plavix: reduced effectiveness in patients who are poor metabolizers of the drug. [cited 2017 Feb]. Available from: https://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm203888.htm
89. European Medicines Agency: summary of product characteristics (Plavix). [cited 2017 Mar]. Available from http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/000174/WC500042189.pdf
90. Levine GN, Bates ER, Blankenship JC, et al. 2011 ACCF/AHA/SCAI guideline for percutaneous coronary intervention: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines and the Society for Cardiovascular Angiography and Interventions. Circulation. 2011;124(23):e574–e651.
91. Amsterdam EA, Wenger NK, Brindis RG, et al. 2014 AHA/ACC guideline for the management of patients with non-ST-elevation acute coronary syndromes: a report of the American College of Cardiology/American Heart Association Task Force on practice guidelines. J Am Coll Cardiol. 2014;64(24):e139–e228.
92. Authors/Task Force m, Windecker S, Kolh P, et al. 2014 ESC/EACTS 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)Developed with the special contribution of the European Association of Percutaneous Cardiovascular Interventions (EAPCI). Eur Heart J 2014;35(37):2541–2619.
93. Roffi M, Patrono C, Collet JP, et al. 2015 ESC guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation: task force for the management of acute coronary syndromes in patients presenting without persistent st-segment elevation of the European Society of Cardiology (ESC). Eur Heart J. 2016;37(3):267–315.
94. Hochholzer W, Trenk D, Fromm MF, et al. 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. J Am Coll Cardiol. 2010;55(22):2427–2434.
95. Capodanno D, Angiolillo DJ. Pretreatment with antiplatelet drugs in invasively managed patients with coronary artery disease in the contemporary era: review of the evidence and practice guidelines. Circ Cardiovasc Interv. 2015;8(3):e002301.
96. Rollini F, Franchi F, Angiolillo DJ. Switching P2Y12-receptor inhibitors in patients with coronary artery disease. Nat Rev Cardiol. 2016;13(1):11–27.
97. Saracini C, Vestrini A, Galora S, et al. Pharmacogenetics of clopidogrel: comparison between a standard and a rapid genetic testing. Genet Test Mol Biomarkers. 2012;16(6):500–503.
98. Chae H, Kim M, Koh YS, et al. Feasibility of a microarray-based point-of-care CYP2C19 genotyping test for predicting clopidogrel on-treatment platelet reactivity. Biomed Res Int. 2013;154073:2013.
99. Horenstein RB, Madabushi R, Zineh I, et al. Effectiveness of clopidogrel dose escalation to normalize active metabolite exposure and antiplatelet effects in CYP2C19 poor metabolizers. J Clin Pharmacol. 2014;54(8):865–873.
100. Mega JL, Hochholzer W, Frelinger AL, 3rd, et al. Dosing clopidogrel based on CYP2C19 genotype and the effect on platelet reactivity in patients with stable cardiovascular disease. JAMA. 2011;306(20):2221–2228.
101. Price MJ, Murray SS, Angiolillo DJ, et al. Influence of genetic polymorphisms on the effect of high- and standard-dose clopidogrel after percutaneous coronary intervention: the GIFT (Genotype Information and Functional Testing) study. J Am Coll Cardiol. 2012;59(22):1928–1937.
102. Zhang L, Yang J, Zhu X, et al. Effect of high-dose clopidogrel according to CYP2C19*2 genotype in patients undergoing percutaneous coronary intervention- a systematic review and meta-analysis. Thromb Res. 2015;135(3):449–458.
103. Alexopoulos D, Dimitropoulos G, Davlouros P, et al. Prasugrel overcomes high on-clopidogrel platelet reactivity post-stenting more effectively than high-dose (150-mg) clopidogrel: the importance of CYP2C19*2 genotyping. JACC Cardiovasc Interv. 2011;4(4):403–410.
104. So DY, Wells GA, McPherson R, et al. A prospective randomized evaluation of a pharmacogenomic approach to antiplatelet therapy among patients with ST-elevation myocardial infarction: the RAPID STEMI study. Pharmacogenomics J. 2016;16(1):71–78.
105. Rollini F, Franchi F, Cho JR, et al. A head-to-head pharmacodynamic comparison of prasugrel vs. ticagrelor after switching from clopidogrel in patients with coronary artery disease: results of a prospective randomized study. Eur Heart J. 2016;37(35):2722–2730.
106. Sorich MJ, Vitry A, Ward MB, et al. Prasugrel vs. clopidogrel for cytochrome P450 2C19-genotyped subgroups: integration of the TRITON-TIMI 38 trial data. J Thromb Haemost. 2010;8(8):1678–1684.
107. Goto S. Cilostazol: potential mechanism of action for antithrombotic effects accompanied by a low rate of bleeding. Atheroscler Suppl. 2005;6(4):3–11.
108. Hwang SJ, Jeong YH, Kim IS, et al. Cytochrome 2C19 polymorphism and response to adjunctive cilostazol versus high maintenance-dose clopidogrel in patients undergoing percutaneous coronary intervention. Circ Cardiovasc Interv. 2010;3(5):450–459.
109. Kim IS, Jeong YH, Park Y, et al. Platelet inhibition by adjunctive cilostazol versus high maintenance-dose clopidogrel in patients with acute myocardial infarction according to cytochrome P450 2C19 genotype. JACC Cardiovasc Interv. 2011;4(4):381–391.
110. Angiolillo DJ, Capodanno D, Goto S. Platelet thrombin receptor antagonism and atherothrombosis. Eur Heart J. 2010;31(1):17–28.
111. Morrow DA, Braunwald E, Bonaca MP, et al. Vorapaxar in the secondary prevention of atherothrombotic events. N Engl J Med. 2012;366(15):1404–1413.
112. Shen DL, Wang B, Bai J, et al. Clinical value of CYP2C19 genetic testing for guiding the antiplatelet therapy in a Chinese population. J Cardiovasc Pharmacol. 2016;67(3):232–236.
113. Xie X, Ma YT, Yang YN, et al. Personalized antiplatelet therapy according to CYP2C19 genotype after percutaneous coronary intervention: a randomized control trial. Int J Cardiol. 2013;168(4):3736–3740.
114. Deiman BA, Tonino PA, Kouhestani K, et al. Reduced number of cardiovascular events and increased cost-effectiveness by genotype-guided antiplatelet therapy in patients undergoing percutaneous coronary interventions in the Netherlands. Neth Heart J. 2016;24(10):589–599.
115. Sanchez-Ramos J, Davila-Fajardo CL, Toledo Frias P, et al. Results of genotype-guided antiplatelet therapy in patients who undergone percutaneous coronary intervention with stent. Int J Cardiol. 2016;225:289–295.
116. Cavallari LH, Magvanjav O, Anderson RD, et al. Clinical implementation of CYP2C19 genotype guided antiplatelet therapy reduces cardiovascular events after PCI. Circulation. 2015;132:A11802.
117. Weitzel KW, Alexander M, Bernhardt BA, et al. The IGNITE network: a model for genomic medicine implementation and research. BMC Med Genomics. 2016;9:1.
118. Cavallari LH, Denny JC, Lee CR, et al. Prospective clinical implementation of CYP2C19-genotype guided antiplatelet therapy after PCI: a multi-site investigation of MACE outcomes in a real-world setting. Circulation. 2016;134(25):e711–e712.
119. Weitzel KW, Elsey AR, Langaee TY, et al. Clinical pharmacogenetics implementation: approaches, successes, and challenges. Am J Med Genet C Semin Med Genet. 2014;166C(1):56–67.
120. Cavallari LH, Lee CR, Duarte JD, et al. Implementation of inpatient models of pharmacogenetics programs. Am J Health Syst Pharm. 2016;73(23):1944–1954.
121. Trenk D, Stone GW, Gawaz M, et al. A randomized trial of prasugrel versus clopidogrel in patients with high platelet reactivity on clopidogrel after elective percutaneous coronary intervention with implantation of drug-eluting stents: results of the TRIGGER-PCI (Testing platelet reactivity in patients undergoing elective stent placement on clopidogrel to guide alternative therapy with prasugrel) study. J Am Coll Cardiol. 2012;59(24):2159–2164.
122. Price MJ, Berger PB, Teirstein PS, et al. Standard- vs high-dose clopidogrel based on platelet function testing after percutaneous coronary intervention: the GRAVITAS randomized trial. JAMA. 2011;305(11):1097–1105.
123. Cayla G, Cuisset T, Silvain J, et al. Platelet function monitoring to adjust antiplatelet therapy in elderly patients stented for an acute coronary syndrome (ANTARCTIC): an open-label, blinded-endpoint, randomised controlled superiority trial. Lancet. 2016;388(10055):2015–2022.
124. Collet JP, Cuisset T, Range G, et al. Bedside monitoring to adjust antiplatelet therapy for coronary stenting. N Engl J Med. 2012;367(22):2100–2109.
125. Franchi F, Rollini F, Cho JR, et al. Platelet function testing in contemporary clinical and interventional practice. Curr Treat Options Cardiovasc Med. 2014;16(5):300.
126. Sibbing D, Aradi D, Jacobshagen C, et al. A randomised trial on platelet function-guided de-escalation of antiplatelet treatment in ACS patients undergoing PCI. Rationale and design of the testing responsiveness to platelet inhibition on chronic antiplatelet treatment for acute coronary syndromes (TROPICAL-ACS) trial. Thromb Haemost. 2017;117(1):188–195.
127. Mehran R, Rao SV, Bhatt DL, et al. Standardized bleeding definitions for cardiovascular clinical trials: a consensus report from the Bleeding Academic Research Consortium. Circulation. 2011;123(23):2736–2747.