The role of platelet reactivity and genotype testing in the prevention of atherothrombotic cardiovascular events remains unproven

Circulation

Volumn 125, Issue 10, 2012, Pages 1288-1303

  Krishna, Vamsi ^a   Diamond, George A ^a   Kaul, Sanjay ^a  

^a CEDARS SINAI MEDICAL CENTER   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ACETYLSALICYLIC ACID; CALCIUM CHANNEL BLOCKING AGENT; CILOSTAZOL; CLOPIDOGREL; CYTOCHROME P450 2C19; OMEPRAZOLE; PRASUGREL; PROTON PUMP INHIBITOR; TICAGRELOR; ANTITHROMBOCYTIC AGENT; CYP2C19 PROTEIN, HUMAN; DRUG DERIVATIVE; FIBRINOLYTIC AGENT; P2RY12 PROTEIN, HUMAN; PURINERGIC P2Y RECEPTOR ANTAGONIST; PURINERGIC P2Y12 RECEPTOR; TICLOPIDINE; UNSPECIFIC MONOOXYGENASE;

ACUTE CORONARY SYNDROME; ANTICOAGULATION; ARTICLE; BLEEDING; BLOOD CLOTTING PARAMETERS; DECISION MAKING; DRUG MECHANISM; DRUG METABOLISM; GENETIC SCREENING; GENETIC VARIABILITY; GENOTYPE; HUMAN; PERCUTANEOUS CORONARY INTERVENTION; PLATELET REACTIVITY; PREVALENCE; PRIORITY JOURNAL; PROGNOSIS; THROMBOCYTE FUNCTION; THROMBOSIS; TREATMENT OUTCOME; DRUG COMBINATION; GENETICS; METABOLISM; PHARMACOGENETICS; RISK FACTOR; STANDARD;

ARYL HYDROCARBON HYDROXYLASES; ASPIRIN; DRUG THERAPY, COMBINATION; FIBRINOLYTIC AGENTS; GENETIC TESTING; GENOTYPE; HUMANS; PHARMACOGENETICS; PLATELET AGGREGATION INHIBITORS; PLATELET FUNCTION TESTS; PREVALENCE; PROGNOSIS; PURINERGIC P2Y RECEPTOR ANTAGONISTS; RECEPTORS, PURINERGIC P2Y12; RISK FACTORS; THROMBOSIS; TICLOPIDINE;

EID: 84858430231     PISSN: 00097322     EISSN: 15244539     Source Type: Journal    
DOI: 10.1161/CIRCULATIONAHA.111.075242     Document Type: Article

References (76)

1. Hulot JS, Bura A, Villard E, Azizi M, Remones V, Goyenvalle C, Aiach M, Lechat P, Gaussem P. Cytochrome P450 2C19 loss-of function polymorphism is a major determinant of clopidogrel responsiveness in healthy subjects. Blood. 2006;108:2244-2247. (Pubitemid 44497506)
2. Angiolillo DJ, Fernandez-Ortiz A, Bernardo E, Alfonso F, Macaya C, Bass TA, Costa MA. Variability in individual responsiveness to clopidogrel: clinical implications, management, and future perspectives. J Am Coll Cardiol. 2007;49:1505-1516. (Pubitemid 46517957)
3. Mega JL, Close SL, Wiviott SD, Shen L, Hockett RD, Brandt JT, Walker JR, Antman EM, Macias W, Braunwald E, Sabatine MS. Cytochrome p-450 polymorphisms and response to clopidogrel. N Engl J Med. 2009;360:354-362.
4. Simon T, Verstuyft C, Mary-Krause M, Quteineh L, Drouet E, Méneveau N, Steg PG, Ferrières J, Danchin N, Becquemont L; French Registry of Acute ST-Elevation and Non-ST-Elevation Myocardial Infarction (FAST-MI) Investigators. Genetic determinants of response to clopidogrel and cardiovascular events. N Engl J Med. 2009;360:363-375.
5. Aradi D, Komócsi A, Vorobcsuk A, Rideg O, Tokés-Füzesi M, Magyarlaki T, Horváth IG, Serebruany VL. Prognostic significance of high on-clopidogrel platelet reactivity after percutaneous coronary intervention: systematic review and meta-analysis. Am Heart J. 2010;160:543-551.
6. Patti G, Nusca A, Mangiacapra F, Gatto L, D'Ambrosio A, Di Sciascio G. Point-of-care measurement of clopidogrel responsiveness predicts clinical outcome in patients undergoing percutaneous coronary intervention: results of the ARMYDA-PRO (Antiplatelet Therapy for Reduction of Myocardial Damage During Angioplasty-Platelet Reactivity Predicts Outcome) study. J Am Coll Cardiol. 2008;52:1128-1133.
7. Bonello L, Tantry US, Marcucci R, Blindt R, Angiolillo DJ, Becker R, Bhatt DL, Cattaneo M, Collet JP, Cuisset T, Gachet C, Montalescot G, Jennings LK, Kereiakes D, Sibbing D, Trenk D, Van Werkum JW, Paganelli F, Price MJ, Waksman R, Gurbel PA; Working Group on High On-Treatment Platelet Reactivity. Consensus and future directions on the definition of high on-treatment platelet reactivity to adenosine diphosphate. J Am Coll Cardiol. 2010;56:919-933.
8. Campo G, Parrinello G, Ferraresi P, Lunghi B, Tebaldi M, Miccoli M, Marchesini J, Bernardi F, Ferrari R, Valgimigli M. Prospective evaluation of on-clopidogrel platelet reactivity over time in patients treated with percutaneous coronary intervention relationship with gene polymorphisms and clinical outcome. J Am Coll Cardiol. 2011;57:2474-2483.
9. Shuldiner AR, O'Connell JR, Bliden KP, Gandhi A, Ryan K, Horenstein RB, Damcott CM, Pakyz R, Tantry US, Gibson Q, Pollin TI, Post W, Parsa A, Mitchell BD, Faraday N, Herzog W, Gurbel PA. Association of cytochrome P450 2C19 genotype with the antiplatelet effect and clinical efficacy of clopidogrel therapy. JAMA. 2009;302:849-857.
10. *2 loss-of-function allele or proton pump inhibitor co-administration: a systematic meta-analysis. J Am Coll Cardiol. 2010;56:134-143.
11. Mega JL, Simon T, Collet JP, Anderson JL, Antman EM, Bliden K, Cannon CP, Danchin N, Giusti B, Gurbel P, Horne BD, Hulot JS, Kastrati A, Montalescot G, Neumann FJ, Shen L, Sibbing D, Steg PG, Trenk D, Wiviott SD, Sabatine MS. Reduced-function CYP2C19 genotype and risk of adverse clinical outcomes among patients treated with clopidogrel predominantly for PCI: a meta-analysis. JAMA. 2010;304:1821-1830.
12. 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/ucm203888htm. Accessed October 13, 2011.
13. Holmes DR Jr, Dehmer GJ, Kaul S, Leifer D, O'Gara PT, Stein CM; Society for Cardiovascular Angiography and Interventions; Society of Thoracic Surgeons; Writing Committee Members. 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. Circulation. 2010;122:537-557.
14. Breet NJ, van Werkum JW, Bouman HJ, Kelder JC, Ruven HJ, Bal ET, Deneer VH, Harmsze AM, van der Heyden JA, Rensing BJ, Suttorp MJ, Hackeng CM, ten Berg JM. Comparison of platelet function tests in predicting clinical outcome in patients undergoing coronary stent implantation. JAMA. 2010;303:754-762.
15. Pare G, Mehta S, Yusuf S, Phil D, Anand S, Connolly S, Hirsh J, Simonsen K, Bhatt D, Fox K, Eikelboom J. Effects of CYP2C19 genotype and outcomes on clopidogrel treatment. N Engl J Med. 2010;363:1704-1714.
16. Mega JL, Close SL, Wiviott SD, Shen L, Walker JR, Simon T, Antman EM, Braunwald E, Sabatine MS. 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;376:1312-1319.
17. Wallentin L, James S, Storey RF, Armstrong M, Barratt BJ, Horrow J, Husted S, Katus H, Steg PG, Shah SH, Becker RC; PLATO Investigators. 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;376:1320-1328.
18. Price MJ, Berger PB, Teirstein PS, Tanguay JF, Angiolillo DJ, Spriggs D, Puri S, Robbins M, Garratt KN, Bertrand OF, Stillablower ME, Aragon JR, Kandzari DE, Stinis CT, Lee MS, Manoukian SV, Cannon CP, Schork NJ, Topol EJ; GRAVITAS Investigators. Standard-vs high-dose clopidogrel based on platelet function testing after percutaneous coronary intervention: the GRAVITAS randomized trial. JAMA. 2011;305:1097-1105.
19. Kazui M, Nishiya Y, Ishizuka T, Hagihara K, Farid NA, Okazaki O, Ikeda T, Kurihara A. Identification of the human cytochrome P450 enzymes involved in the two oxidative steps in the bioactivation of clopidogrel to its pharmacologically active metabolite. Drug Metab Dispos. 2009;38:92-99.
20. Steinhubl SR. Genotyping, clopidogrel metabolism, and the search for therapeutic window of thienopyridines. Circulation. 2010;121:481-483.
21. Man M, Farmen M, Dumaual C, Teng CH, Moser B, Irie S, Noh GJ, Njau R, Close S, Wise S, Hockett R. 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;50:929-940.
22. Luo HR, Poland RE, Lin KM, Wan YJ. Genetic polymorphism of cytochrome P450 2C19 in Mexican Americans: a cross-ethnic comparative study. Clin Pharmacol Ther. 2006;80:33-40. (Pubitemid 43946839)
23. Collet JP, Hulot JS, Pena A, Villard E, Esteve JB, Silvain J, Payot L, Brugier D, Cayla G, Beygui F, Bensimon G, Funck-Brentano C, Montalescot G. Cytochrome P450 2C19 polymorphism in young patients treated with clopidogrel after myocardial infarction: a cohort study. Lancet. 2009;373:309-317.
24. *17 allelic variant, platelet aggregation, bleeding events, and stent thrombosis in clopidogrel-treated patients with coronary stent placement. Circulation. 2010;121:512-518.
25. Bura A, Bachelot-Loza C, Ali FD, Aiach M, Gaussem P. Role of the P2Y12 gene polymorphism in platelet responsiveness to clopidogrel in healthy subjects. J Thromb Haemost. 2006;4:2096-2097. (Pubitemid 44226807)
26. Bouman HJ, Schömig E, van Werkum JW, Velder J, Hackeng CM, Hirschhäuser C, Waldmann C, Schmalz HG, ten Berg JM, Taubert D. Paraoxonase-1 is a major determinant of clopidogrel efficacy. Nat Med. 2011;17:110-116.
27. Sibbing D, Koch W, Massberg S, Byrne RA, Mehilli J, Schulz S, Mayer K, Bernlochner I, Schömig A, Kastrati A. No association of paraoxonase-1 Q192R genotypes with platelet response to clopidogrel and risk of stent thrombosis after coronary stenting. Eur Heart J. 2011;32:1605-1613.
28. Fontana P, James R, Barazer I, Berdague P, Schved JF, Rebsamen M, Vuilleumier N, Reny JL. Relationship between paraoxonase-1 activity, its Q192R genetic variant and clopidogrel responsiveness in the ADRIE study. J Thromb Haemost. 2011;9:1664-1666.
29. Trenk D, Hochholzer W, Fromm MF, Zolk O, Valina CM, Stratz C, Neumann FJ. Paraoxonase-1 Q192R polymorphism and antiplatelet effects of clopidogrel in patients undergoing elective coronary stent placement. Circ Cardiovasc Genet. 2011;4:429-436.
30. Rideg O, Komócsi A, Magyarlaki T, Tokés-Füzesi M, Miseta A, Kovács GL, Aradi D. Impact of genetic variants on post-clopidogrel platelet reactivity in patients after elective percutaneous coronary intervention. Pharmacogenomics. 2011;12:1269-1280.
31. Hulot JS, Collet JP, Cayla G, Silvain J, Allanic F, Bellemain-Appaix A, Scott ST, Montalescot G. CYP2C19 but not PON1 genetic variants influence clopidogrel pharmacokinetics, pharmacodynamics and clinical efficacy in post-myocardial infarction patients. Circ Cardiovasc Interv. 2011;4:422-428.
32. Pepe MS, Janes H, Longton G, Leisenring W, Newcomb P. Limitations of the odds ratio in gauging the performance of a diagnostic, prognostic, or screening marker. Am J Epidemiol. 2004;159:882-890. (Pubitemid 38657490)
33. Greenland P, O'Malley PG. When is a new prediction marker useful? A consideration of lipoprotein-associated phospholipase A2 and C-reactive protein for stroke risk. Arch Intern Med. 2005;165:2454-2456. (Pubitemid 41720004)
34. Cook NR. Use and misuse of the receiver operating characteristic curve in risk prediction. Circulation. 2007;115:928-935. (Pubitemid 46294733)
35. Pencina MJ, D'Agostino RB Sr, D'Agostino RB Jr, Vasan RS. Evaluating the added predictive ability of a new marker: from area under the ROC curve to reclassification and beyond. Stat Med. 2008;27:157-172. (Pubitemid 351193639)
36. Diamond GA. What price perfection? Calibration and discrimination of clinical prediction models. J Clin Epidemiol. 1992;45:85-88.
37. Frere C, Cuisset T, Quilici J, Camoin L, Carvajal J, Morange PE, Lambert M, Juhan-Vague I, Bonnet JL, Alessi MC. ADP-induced platelet aggregation and platelet reactivity index VASP are good predictive markers for clinical outcomes in non-ST elevation acute coronary syndrome. Thromb Haemost. 2007;98:838-843. (Pubitemid 47555077)
38. Sibbing D, Morath T, Braun S, Stegherr J, Mehilli J, Vogt W, Schömig A, Kastrati A, von Beckerath N. Clopidogrel response status assessed with Multiplate point-of-care analysis and the incidence and timing of stent thrombosis over six months following coronary stenting. Thromb Haemost. 2010;103:151-159.
39. Gori AM, Marcucci R, Paniccia R, Giusti B, Fedi S, Antonucci E, Buonamici P, Antoniucci D, Gensini GF, Abbate R. Thrombotic events in high risk patients are predicted by evaluating different pathways of platelet function. Thromb Haemost. 2008;100:1136-1145.
40. Testing Platelet Reactivity in Patients Undergoing Elective Stent Placement on Clopidogrel to Guide Alternative Therapy With Prasugrel (TRIGGER-PCI). http://clinicaltrials.gov/ct2/show/NCT00910299. Accessed October 13, 2011.
41. Sibbing D, Steinhubl SR, Schulz S, Schömig A, Kastrati A. Platelet aggregation and its association with stent thrombosis and bleeding in clopidogrel-treated patients: initial evidence of a therapeutic window. J Am Coll Cardiol. 2010;56:317-318.
42. Tantry US, Bliden KP, Wei C, Storey RF, Armstrong M, Butler K, Gurbel PA. 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;3:556-566.
43. Patti G, Pasceri V, Vizzi V, Ricottini E, Di Sciascio G. Usefulness of platelet response to clopidogrel by point-of-care testing to predict bleeding outcomes in patients undergoing percutaneous coronary intervention (from the Antiplatelet Therapy for Reduction of Myocardial Damage During Angioplasty-Bleeding Study). Am J Cardiol. 2011;107:995-1000.
44. Hochholzer W, Trenk D, Fromm MF, Valina CM, Stratz C, Bestehorn HP, Büttner HJ, Neumann FJ. Impact of cytochrome P450 2C19 loss-offunction 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;55:2427-2434.
45. *2 polymorphism and cardiovascular recurrences in patients taking clopidogrel: a meta-analysis. Pharmacogenomics J. 2011;11:199-206.
46. Price MJ. Genotype Information and Functional Testing (GIFT): GRAVITAS gene substudy. Paper presented at: American College of Cardiology 2011 Scientific Sessions; April 5, 2011; New Orleans, LA. http://www.theheart.org/ article/1208199.do.
47. Bauer T, Bouman HJ, van Werkum JW, Ford NF, ten Berg JM, Taubert D. Impact of CYP2C19 variant genotypes on clinical efficacy of antiplatelet treatment with clopidogrel: systematic review and meta-analysis. BMJ. 2011;343:d4588.
48. Ioannidis J P A, Ntzani EE, Trikalinos TA, Contopoulos-Ioannidis DG. Replication validity of genetic association studies. Nat Genet. 2001;29:306-309. (Pubitemid 33096456)
49. Lau WC, Waskell LA, Watkins PB, Neer CJ, Horowitz K, Hopp AS, Tait AR, Carville DG, Buyer KE, Bates ER. Atorvastatin reduced the ability of clopidogrel to inhibit platelet aggregation: a new drug-drug interaction. Circulation. 2003;107:32-37. (Pubitemid 36070929)
50. Siller-Matula JM, Lang I, Christ G, Jilma B. Calcium-channel blockers reduce the antiplatelet effect of clopidogrel. J Am Coll Cardiol. 2008;52:1557-1563.
51. Juurlink DN, Gomes T, Ko DT, Szmitko PE, Austin PC, Tu JV, Henry DA, Kopp A, Mamdani MM. A population-based study of the drug interaction between proton pump inhibitors and clopidogrel. CMAJ. 2009;180:713-718.
52. Ho PM, Maddox TM, Wang L, Fihn SD, Jesse RL, Peterson ED, Rumsfeld JS. Risk of adverse outcomes associated with concomitant use of clopidogrel and proton pump inhibitors following acute coronary syndrome. JAMA. 2009;301:937-944.
53. Aronow HD, Steinhubl SR, Brennan DM, Berger PB, Topol EJ; CREDO Investigators. Bleeding risk associated with 1 year of dual antiplatelet therapy after percutaneous coronary intervention: insights from the Clopidogrel for the Reduction of Events During Observation (CREDO) trial. Am Heart J. 2009;157:369-374.
54. Hankey GJ, Hacke W, Easton JD, Johnston SC, Mas JL, Brennan DM, Bhatt DL, Fox KA, Topol EJ; CHARISMA Trial Investigators. Effect of clopidogrel on the rate and functional severity of stroke among high vascular risk patients: a prespecified substudy of the Clopidogrel for High Atherothrombotic Risk and Ischemic Stabilization, Management and Avoidance (CHARISMA) trial. Stroke. 2010;41:1679-1683.
55. O'Donoghue ML, Braunwald E, Antman EM, Murphy SA, Bates ER, Rozenman Y, Michelson AD, Hautvast RW, Ver Lee PN, Close SL, Shen L, Mega JL, Sabatine MS, Wiviott SD. Pharmacodynamic effect and clinical efficacy of clopidogrel and prasugrel with or without a proton-pump inhibitor: an analysis of two randomised trials. Lancet. 2009;374:989-997.
56. Simon T, Steg PG, Gilard M, Blanchard D, Bonello L, Hanssen M, Lardoux H, Coste P, Lefèvre T, Drouet E, Mulak G, Bataille V, Ferrières J, Verstuyft C, Danchin N. Clinical events as a function of proton pump inhibitor use, clopidogrel use, and cytochrome P450 2C19 genotype in a large nationwide cohort of acute myocardial infarction: results from the French Registry of Acute ST-Elevation and Non-ST-Elevation Myocardial Infarction (FAST-MI) registry. Circulation. 2011;123:474-482.
57. Bhatt DL, Cryer BL, Contant CF, Cohen M, Lanas A, Schnitzer TJ, Shook TL, Lapuerta P, Goldsmith MA, Laine L, Scirica BM, Murphy SA, Cannon CP. Clopidogrel with or without omeprazole in coronary artery disease. N Engl J Med. 2010;363:1909-1917.
58. Abraham NS, Hlatky MA, Antman EM, Bhatt DL, Bjorkman DJ, Clark CB, Furberg CD, Johnson DA, Kahi CJ, Laine L, Mahaffey KW, Quigley EM, Scheiman J, Sperling LS, Tomaselli GF; ACCF/ACG/AHA. ACCF/ACG/AHA 2010 expert consensus document on the concomitant use of proton pump inhibitors and thienopyridines: a focused update of the ACCF/ACG/AHA 2008 expert consensus document on reducing the gastrointestinal risks of antiplatelet therapy and NSAID use: a Report of the American College of Cardiology Foundation Task Force on Expert Consensus Documents. J Am Coll Cardiol. 2010;56:2051-2066.
59. Angiolillo DJ, Ueno M. Optimizing platelet inhibition in clopidogrel poor metabolizers: therapeutic options and practical considerations. J Am Coll Cardiol Cardiovasc Interv. 2011;4:411-414.
60. Bonello L, Camoin-Jau L, Arques S, Boyer C, Panagides D, Wittenberg O, Simeoni MC, Barragan P, Dignat-George F, Paganelli F. Adjusted clopidogrel loading doses according to vasodilatorstimulated 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. (Pubitemid 351447314)
61. Bonello L, Camoin-Jau L, Armero S, Com O, Arques S, Burignat-Bonello C, Giacomoni MP, Bonello R, Collet F, Rossi P, Barragan P, Dignat-George F, Paganelli F. Tailored clopidogrel loading dose according to platelet reactivity monitoring to prevent acute and subacute stent thrombosis. Am J Cardiol. 2009;103:5-10.
62. Jeong YH, Lee SW, Choi BR, Kim IS, Seo MK, Kwak CH, Hwang JY, Park SW. Randomized comparison of adjunctive cilostazol versus high maintenance dose clopidogrel in patients with high posttreatment platelet reactivity: results of the ACCEL-RESISTANCE (Adjunctive Cilostazol Versus High Maintenance Dose Clopidogrel in Patients With Clopidogrel Resistance) randomized study. J Am Coll Cardiol. 2009;53:1101-1109.
63. Gurbel PA, Bliden KP, Butler K, Antonino MJ, Wei C, Teng R, Rasmussen L, Storey RF, Nielsen T, Eikelboom JW, Sabe-Affaki G, Husted S, Kereiakes DJ, Henderson D, Patel DV, Tantry US. Response to Ticagrelor in Clopidogrel Non-responders and Responders and the Effect of Switching Therapies: the RESPOND Study. Circulation. 2010;121:1188-1199.
64. *2 genotype: first experience in patients. J Thromb Haemost. 2010;8:43-53.
65. Cuisset T, Frere C, Quilici J, Morange PE, Mouret JP, Bali L, Moro PJ, Lambert M, Alessi MC, Bonnet JL. Glycoprotein IIb/IIIa inhibitors improve outcome after coronary stenting in clopidogrel nonresponders: a prospective, randomized study. JACC Cardiovasc Interv. 2008;6:649-653.
66. Valgimigli M, Campo G, de Cesare N, Meliga E, Vranckx P, Furgieri A, Angiolillo DJ, Sabatè M, Hamon M, Repetto A, Colangelo S, Brugaletta S, Parrinello G, Percoco G, Ferrari R; Tailoring Treatment With Tirofiban in Patients Showing Resistance to Aspirin and/or Resistance to Clopidogrel (3T/2R) Investigators. Intensifying platelet inhibition with tirofiban in poor responders to aspirin, clopidogrel, or both agents undergoing elective coronary intervention: results from the double-blind, prospective, randomized Tailoring Treatment with Tirofiban in Patients Showing Resistance to Aspirin and/or Resistance to Clopidogrel study. Circulation. 2009;119:3215-3222.
67. Price MJ, Angiolillo DJ, Teirstein PS, Lillie E, Manoukian SV, Berger PB, Tanguay JF, Cannon CP, Topol EJ. Platelet reactivity and cardiovascular outcomes after percutaneous coronary intervention: a timedependent analysis of the Gauging Responsiveness With a VerifyNow P2Y12 Assay: Impact on Thrombosis and Safety (GRAVITAS) trial. Circulation. 2011;10:1132-1137.
68. Parodi G, Marcucci R, Valenti R, Gori AM, Migliorini A, Giusti B, Buonamici P, Gensini GF, Abbate R, Antoniucci D. High residual platelet reactivity after clopidogrel loading and long-term cardiovascular events among patients with acute coronary syndromes undergoing PCI. JAMA. 2011;306:1215-1223.
69. *2 loss of function polymorphism. J Am Coll Cardiol. 2010;56:1630-1636.
70. Collet JP, Hulot JS, Anzaha G, Pena A, Chastre T, Caron C, Silvain J, Cayla G, Bellemain-Appaix A, Vignalou JB, Galier S, Barthélémy O, Beygui F, Gallois V, Montalescot G; CLOVIS-2 Investigators. High doses of clopidogrel to overcome genetic resistance: the randomized crossover CLOVIS-2 (Clopidogrel and Response Variability Investigation Study 2). JACC Cardiovasc Interv. 2011;4:392-402.
71. Park KW, Park JJ, Lee SP, Oh IY, Suh JW, Yang HM, Lee HY, Kang HJ, Cho YS, Koo BK, Youn TJ, Chae IH, Choi DJ, Oh BH, Park YB, Kim HS. Cilostazol attenuates on-treatment platelet reactivity in patients with CYP2C19 loss of function alleles receiving dual antiplatelet therapy: a genetic substudy of the CILON-T randomized controlled trial. Heart. 2011;97:641-647.
72. Kim IS, Jeong YH, Park Y, Park KS, Yun SE, Park JR, Hwang SJ, Koh EH, Kwak CH, Hwang JY, Kim S. 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;4:381-391.
73. *2 genotyping. JACC Cardiovasc Interv. 2011;4:403-410.
74. Mega JL, Hochholzer W, Frelinger AL, Kluk MJ, Angiolillo DJ, Kereiaker DJ, isserman S, Rogers WJ, Ruff CT, Contant C, Pencina MJ, Scirica BM, Longtine JA, Michelson AD, Sabatine MS. Dosing clopidogrel based on CYP2C19 genotype and the effect on platelet reactivity in patients with stable cardiovascular disease. JAMA. 2011;306:2221-2228.
75. Levine GN, Bates ER, Blankenship JC, Bailey SR, Bittl JA, Cercek B, Chambers CE, Ellis SG, Guyton RA, Hollenberg SM, Khot UN, Lange RA, Mauri L, Mehran R, Moussa ID, Mukherjee D, Nallamothu BK, Ting HH. 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:e574-e651.
76. Bonello L, Pansieri M, Mancini J, Bonello R, Maillard L, Barnay P, Rossi P, Ait-Mokhtar O, Jouve B, Collet F, Peyre JP, Wittenberg O, de Labriolle A, Camilleri E, Cheneau E, Cabassome E, Dignat-George F, Camoin-Jau L, Paganelli F. High on-treatment platelet reactivity after prasugrel loading dose and cardiovascular events after percutaneous coronary intervention in acute coronary syndromes. J Am Coll Cardiol. 2011;58:467-473.