ADP Receptor Antagonists

Platelets

Volumn , Issue , 2013, Pages 1117-1138

  Cattaneo, Marco ^a  

^a UNIVERSITY OF MILAN   (Italy)

Author keywords

[No Author keywords available]

Indexed keywords

EID: 84882671409     PISSN: None     EISSN: None     Source Type: Book    
DOI: 10.1016/B978-0-12-387837-3.00054-7     Document Type: Chapter

References (209)

1. Cattaneo M, Gachet C. ADP receptors and clinical bleeding disorders. Arterioscler Thromb Vasc Biol 1999, 19:2281-2285.
2. 12 receptor for adenosine diphosphate: congenital and drug-induced defects. Blood 2011, 117:2102-2112.
3. Cattaneo M. Platelet P2 receptors: old and new targets for antithrombotic drugs. Expert Rev Cardiovasc Ther 2007, 5:45-55.
4. Helft G, Osende JI, Worthley SG, et al. Acute antithrombotic effect of a front-loaded regimen of clopidogrel in patients with atherosclerosis on aspirin. Arterioscler Thromb Vasc Biol 2000, 20:2316-2321.
5. Hochholzer W, Trenk D, Frundi D, et al. Time dependence of platelet inhibition after a 600-mg loading dose of clopidogrel in a large, unselected cohort of candidates for percutaneous coronary intervention. Circulation 2005, 111:2560-2564.
6. Savi P, Herbert JM. Clopidogrel and ticlopidine: P2Y12 adenosine diphosphate-receptor antagonists for the prevention of atherothrombosis. Sem Thromb Hemost 2005, 31:174-183.
7. Farid NA, Kurihara A, Wrighton SA. Metabolism and disposition of the thienopyridine antiplatelet drugs ticlopidine, clopidogrel, and prasugrel in humans. J Clin Pharmacol 2010, 50:126-142.
8. Bouman HJ, Schömig E, van Werkum JW. Paraoxonase-1 is a major determinant of clopidogrel efficacy. Nat Med 2011, 17:110-116.
9. 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, 4:422-428.
10. Camps J, Joven J, Mackness B, et al. Paraoxonase-1 and clopidogrel efficacy. Nat Med 2011, 17:1041-1042.
11. Dansette PM, Rosi J, Bertho G, Mansuy D. Paraoxonase-1 and clopidogrel efficacy. Nat Med 2011, 17:1040-1041.
12. Cuisset T, Morange PE, Quilici J, et al. Paraoxonase-1 and clopidogrel efficacy. Nat Med 2011, 17:1039.
13. Fontana P, James R, Barazer I, et al. Relationship between paraoxonase-1 activity, its Q192R genetic variant and clopidogrel responsiveness in the ADRIE study. J Thromb Haemost 2011, 9:1664-1666.
14. 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, 4:429-436.
15. 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, 32:1605-1613.
16. Savi P, Pereillo JM, Uzabiaga MF, et al. Identification and biological activity of the active metabolite of clopidogrel. Thromb Haemost 2000, 84:891-896.
17. Palareti G, Poggi M, Torricelli P, et al. Long-term effects of ticlopidine on fibrinogen and haemorheology in patients with peripheral arterial disease. Thromb Res 1988, 52:621-629.
18. Mazoyer E, Ripoll L, Boisseau MR, Drouet L. How does ticlopidine treatment lower plasma fibrinogen?. Thromb Res 1994, 75:361-370.
19. Hayakawa M, Kuzuya F. Effects of ticlopidine on erythrocyte aggregation in thrombotic disorders. Angiology 1991, 42:747-753.
20. de Lorgeril M, Bordet JC, Salen P, et al. Ticlopidine increases nitric oxide generation in heart-transplant recipients: a possible novel property of ticlopidine. J Cardiovasc Pharmacol 1998, 32:225-230.
21. Savi P, Bernat A, Dumas A, et al. Effect of aspirin and clopidogrel on platelet-dependent tissue factor expression in endothelial cells. Thromb Res 1994, 73:117-124.
22. Piovella F, Ricetti MM, Almasio P, et al. The effect of ticlopidine on human endothelial cells in culture. Thromb Res 1984, 33:323-332.
23. Paradiso-Hardy FL, Angelo CM, Lanctot KL, Cohen EA. Hematologic dyscrasia associated with ticlopidine therapy: evidence for causality. CMAJ 2000, 163:1441-1448.
24. Bennett CL, Weinberg PD, Rozenberg-Ben-Dror K, et al. Thrombotic thrombocytopenic purpura associated with ticlopidine. A review of 60 cases. Ann Intern Med 1998, 128:541-544.
25. Steinhubl SR, Tan WA, Foody JM, Topol EJ. Incidence and clinical course of thrombotic thrombocytopenic purpura due to ticlopidine following coronary stenting. EPISTENT Investigators. Evaluation of Platelet IIb/IIIa Inhibitor for Stenting. JAMA 1999, 281:806-810.
26. Tsai HM, Rice L, Sarode R, et al. Antibody inhibitors to von Willebrand factor metalloproteinase and increased binding of von Willebrand factor to platelets in ticlopidine-associated thrombotic thrombocytopenic purpura. Ann Intern Med 2000, 132:794-799.
27. Meyer B, Staudinger T, Lechner K. Clopidogrel and aplastic anaemia. Lancet 2001, 357:1446-1447.
28. Trivier JM, Caron J, Mahieu M, et al. Fatal aplastic anaemia associated with clopidogrel. Lancet 2001, 357:446.
29. CAPRIE Steering Committee A randomised, blinded, trial of clopidogrel versus aspirin in patients at risk of ischaemic events (CAPRIE). Lancet 1996, 348:1329-1339.
30. Fork FT, Lafolie P, Toth E, Lindgarde F. Gastroduodenal tolerance of 75mg clopidogrel versus 325mg aspirin in healthy volunteers. A gastroscopic study. Scand J Gastroenterol 2000, 35:464-469.
31. Braunwald E, Antman EM, Beasley, et al. ACC/AHA guideline update for the management of patients with unstable angina and non-ST-segment elevation myocardial infarction-2002: summary article: a report of the American college of cardiology/American heart association task force on practice guidelines (committee on the management of patients with unstable Angina). Circulation 2002, 106:1893-1900.
32. Chan FK, Ching JY, Hung LC, et al. Clopidogrel versus aspirin and esomeprazole to prevent recurrent ulcer bleeding. N Engl J Med 2005, 352:238-244.
33. Doggrell SA. Aspirin and esomeprazole are superior to clopidogrel in preventing recurrent ulcer bleeding. Expert Opin Pharmacother 2005, 6:1253-1256.
34. Buresly K, Eisenberg MJ, Zhang X, Pilote L. Bleeding complications associated with combinations of aspirin, thienopyridine derivatives, and warfarin in elderly patients following acute myocardial infarction. Arch Intern Med 2005, 165:784-789.
35. Cattaneo M. Bleeding manifestations of congenital and drug-induced defects of the platelet P2Y12 receptor for adenosine diphosphate. Thromb Haemost 2011, 105(Suppl. 1):S67-S74.
36. Janzon L, Bergqvist D, Boberg J, et al. Prevention of myocardial infarction and stroke in patients with intermittent claudication; effects of ticlopidine. Results from STIMS, the Swedish ticlopidine multicentre study. J Intern Med 1990, 227:301-308.
37. Bergqvist D, Almgren B, Dickinson JP. Reduction of requirement for leg vascular surgery during long-term treatment of claudicant patients with ticlopidine: results from the Swedish ticlopidine multicentre study (STIMS). Eur J Vasc Endovasc Surg 1995, 10:69-76.
38. Balsano F, Rizzon P, Violi F, et al. Antiplatelet treatment with ticlopidine in unstable angina. A controlled multicenter clinical trial. The studio della ticlopidina nell'angina instabile group. Circulation 1990, 82:17-26.
39. Becquemin JP. Effect of ticlopidine on the long-term patency of saphenous-vein bypass grafts in the legs. Etude de la ticlopidine apres pontage femoro-poplite and the association universitaire de recherche en chirurgie. N Engl J Med 1997, 337:1726-1731.
40. Bhatt DL, Fox KAA, Hacke W, et al. Clopidogrel and aspirin versus aspirin alone for the prevention of atherothrombotic events. N Engl J Med 2006, 354:1706-1717.
41. Cacoub PP, Bhatt DL, Steg PG, et al. Patients with peripheral arterial disease in the CHARISMA trial. Eur Heart J 2009, 30:192-201.
42. Steinhubl SR, Bhatt DL, Brennan DM, et al. CHARISMA investigators. Aspirin to prevent cardiovascular disease: the association of aspirin dose and clopidogrel with thrombosis and bleeding. Ann Intern Med 2009, 150:379-386.
43. Cattaneo M, Lecchi A. Inhibition of the platelet P2Y12 receptor for adenosine diphosphate potentiates the antiplatelet effect of prostacyclin. J Thromb Haemost 2007, 5:577-582.
44. Cattaneo M. What is the best dose of aspirin in association with P2Y12 antagonists?. Heart 2011, 97:263-264.
45. Berger PB, Bhatt DL, Fuster V, et al. Bleeding complications with dual antiplatelet therapy among patients with stable vascular disease or risk factors for vascular disease: results from the Clopidogrel for high atherothrombotic risk and ischemic stabilization, management, and avoidance (CHARISMA) trial. Circulation 2010, 121:2575-2583.
46. Mak KH, Bhatt DL, Shao M, et al. The influence of body mass index on mortality and bleeding among patients with or at high-risk of atherothrombotic disease. Eur Heart J 2009, 30:857-865.
47. Berger JS, Bhatt DL, Steinhubl SR, et al. CHARISMA investigators. Smoking, clopidogrel, and mortality in patients with established cardiovascular disease. Circulation 2009, 120:2337-2344.
48. Gent M, Blakely JA, Easton JD, et al. The Canadian American ticlopidine study (CATS) in thromboembolic stroke. Lancet 1989, 1:1215-1220.
49. Hass WK, Easton JD, Adams HP, et al. A randomized trial comparing ticlopidine hydrochloride with aspirin for the prevention of stroke in high-risk patients. Ticlopidine Aspirin stroke study group. N Engl J Med 1989, 321:501-507.
50. Gorelick PB, Richardson D, Kelly M, et al. Aspirin and ticlopidine for prevention of recurrent stroke in black patients: a randomized trial. JAMA 2003, 289:2947-2957.
51. Hankey GJ, Sudlow CL, Dunbabin DW. Thienopyridine derivatives (ticlopidine, clopidogrel) versus aspirin for preventing stroke and other serious vascular events in high vascular risk patients. Cochrane Database Syst Rev 2000, (2):CD001246.
52. Diener HC, Bogousslavsky J, Brass LM, et al. Aspirin and clopidogrel compared with clopidogrel alone after recent ischaemic stroke or transient ischaemic attack in high-risk patients (MATCH): randomised, double-blind, placebo-controlled trial. Lancet 2004, 364:331-337.
53. Chimowitz MI, Lynn MJ, Derdeyn CP, et al. Stenting versus aggressive medical therapy for intracranial arterial stenosis. N Engl J Med 2011, 365:993-1003.
54. Diener HC, Cunha L, Forbes C, et al. Dipyridamole and acetylsalicylic acid in the secondary prevention of stroke. J Neurol Sci 1996, 143:1-13.
55. The ESPRIT Study Group Aspirin plus dipyridamole versus aspirin alone after cerebral ischaemia of arterial origin (ESPRIT): randomised controlled trial. Lancet 2006, 367:1665-1673.
56. Thijs V, Lemmens R, Fieuws S. Network meta-analysis: simultaneous meta-analysis of common antiplatelet regimens after transient ischaemic attack or stroke. Eur Heart J 2008, 29:1086-1092.
57. Sacco RL, Diener HC, Yusuf S, et al. Aspirin and extended-release dipyridamole versus clopidogrel for recurrent stroke. N Engl J Med 2008, 359:1238-1251.
58. Scrutinio D, Cimminiello C, Marubini E, et al. Ticlopidine versus aspirin after myocardial infarction (STAMI) trial. J Am Coll Cardiol 2001, 37:1259-1265.
59. Sudlow CL, Mason G, Maurice JB, et al. Thienopyridine derivatives versus aspirin for preventing stroke and other serious vascular events in high vascular risk patients. Cochrane Database Syst Rev 2009, (4):CD001246.
60. Squizzato A, Keller T, Romualdi E, Middeldorp S. Clopidogrel plus aspirin versus aspirin alone for preventing cardiovascular disease. Cochrane Database Syst Rev 2011, 19(1):CD005158.
61. Balsano F, Cocchieri S, Libretti G, et al. Ticlopidine in the treatment of intermittent claudication: a 21-month double-blind trial. J Lab Clin Med 1989, 114:84-91.
62. 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.
63. 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, 352:1179-1189.
64. 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, 366:1607-1621.
65. Dose comparisons of clopidogrel and aspirin in acute coronary syndromes. N Engl J Med 2010, 363:930-942. CURRENT-OASIS 7 Investigators.
66. Schomig A, Neumann FJ, Kastrati A, et al. A randomized comparison of antiplatelet and anticoagulant therapy after the placement of coronary-artery stents. N Engl J Med 1996, 334:1084-1089.
67. Bertrand ME, Legrand V, Boland J, et al. Randomized multicenter comparison of conventional anticoagulation versus antiplatelet therapy in unplanned and elective coronary stenting. The full anticoagulation versus aspirin and ticlopidine (fantastic) study. Circulation 1998, 98:1597-1603.
68. Urban P, Macaya C, Rupprecht HJ, et al. Randomized evaluation of anticoagulation versus antiplatelet therapy after coronary stent implantation in high-risk patients: the multicenter aspirin and ticlopidine trial after intracoronary stenting (MATTIS). Circulation 1998, 98:2126-2132.
69. Leon MB, Baim DS, Popma JJ, et al. A clinical trial comparing three antithrombotic-drug regimens after coronary-artery stenting. Stent anticoagulation restenosis study investigators. N Eng. J Med 1998, 339:1665-1671.
70. Mehta SR, Yusuf S, Peters RJ, et al. Clopidogrel in unstable angina to prevent recurrent events trial (CURE) investigators. Effects of pretreatment with clopidogrel and aspirin followed by long-term therapy in patients undergoing percutaneous coronary intervention: the PCI-CURE study. Lancet 2001, 358:527-533.
71. Steinhubl SR, Berger PB, Mann JT, et al. Clopidogrel for the reduction of events during observation. Early and sustained dual oral antiplatelet therapy following percutaneous coronary intervention: a randomized controlled trial. JAMA 2002, 288:2411-2420.
72. Sabatine MS, Cannon CP, Gibson CM, et al. Effect of clopidogrel pretreatment before percutaneous coronary intervention in patients with ST-elevation myocardial infarction treated with fibrinolytics: the PCI-CLARITY study. JAMA 2005, 294:1224-1232.
73. Patti G, Colonna G, Pasceri V, et al. Randomized trial of high loading dose of clopidogrel for reduction of periprocedural myocardial infarction in patients undergoing coronary intervention: results from the ARMYDA-2 (antiplatelet therapy for reduction of MYocardial damage during angioplasty) study. Circulation 2005, 111:2099-2106.
74. Kastrati A, Mehilli J, Schuhlen H, et al. A clinical trial of abciximab in elective percutaneous coronary intervention after pretreatment with clopidogrel. N Engl J Med 2004, 350:232-238.
75. Kastrati A, Mehilli J, Neumann FJ, et al. Abciximab in patients with acute coronary syndromes undergoing percutaneous coronary intervention after clopidogrel pretreatment: the ISAR-REACT 2 randomized trial. JAMA 2006, 295:1531-1538.
76. Bhatt DL, Bertrand ME, Berger PB, et al. Meta-analysis of randomized and registry comparisons of ticlopidine with clopidogrel after stenting. J Am Coll Cardiol 2002, 39:9-14.
77. Mueller C, Roskamm H, Neumann FJ, et al. A randomized comparison of clopidogrel and aspirin versus ticlopidine and aspirin after the placement of coronary artery stents. J Am Coll Cardiol 2003, 41:969-973.
78. Wolak A, Amit G, Cafri C, et al. Increased long term rates of stent thrombosis and mortality in patients given clopidogrel as compared to ticlopidine following coronary stent implantation. Int J Cardiol 2005, 103:293-297.
79. Berger JS, Frye CB, Harshaw Q, et al. Impact of clopidogrel in patients with acute coronary syndromes requiring coronary artery bypass surgery: a multicenter analysis. J Am Coll Cardiol 2008, 52:1693-1701.
80. Vorobcsuk A, Aradi D, Farkasfalvi K, et al. Outcomes of patients receiving clopidogrel prior to cardiac surgery. Int J Cardiol 2012, 156(1):34-40.
81. Purkayastha S, Athanasiou T, Malinovski V, et al. Does clopidogrel affect outcome after coronary artery bypass grafting? A meta-analysis. Heart 2006, 92:531-532.
82. Mehta RH, Roe MT, Mulgund J, et al. Acute clopidogrel use and outcomes in patients with non-ST-segment elevation acute coronary syndromes undergoing coronary artery bypass surgery. J Am Coll Cardiol 2006, 48:281-286.
83. Eagle KA, Guyton RA, Davidoff R, et al. ACC/AHA 2004 guideline update for coronary artery bypass graft surgery: summary article: a report of the American college of cardiology/American heart association task force on practice guidelines (committee to update the 1999 guidelines for coronary artery bypass graft surgery). Circulation 2004, 110:1168-1176.
84. Dunning J, Versteegh M, Fabbri A, et al. Guideline on antiplatelet and anticoagulation management in cardiac surgery. Eur J Cardiothorac Surg 2008, 34:73-92.
85. Nijjer SS, Watson G, Athanasiou T, Malik IS. Safety of clopidogrel being continued until the time of coronary artery bypass grafting in patients with acute coronary syndrome: a meta-analysis of 34 studies. Eur Heart J 2011, 32:2970-2988.
86. ACTIVE Writing Group Clopidogrel plus aspirin versus oral anticoagulation for atrial fibrillation in the atrial fibrillation clopidogrel trial with irbesartan for prevention of vascular events (ACTIVE W): a randomised controlled trial. Lancet 2006, 367:1903-1912.
87. Connolly SJ, Pogue J, Hart RG, et al. Effect of clopidogrel added to aspirin in patients with atrial fibrillation. N Engl J Med 2009, 360:2066-2078.
88. Connolly SJ, Eikelboom JW, Ng J. Net clinical benefit of adding clopidogrel to aspirin therapy in patients with atrial fibrillation for whom vitamin K antagonists are unsuitable. Ann Intern Med 2011, 155:579-586.
89. Osborn G, Escofet X, Da Silva A. Medical adjuvant treatment to increase patency of arteriovenous fistulae and grafts. Cochrane Database Syst Rev 2008, (4):CD002786.
90. Dember LM, Beck GJ, Allon M, et al. Effect of clopidogrel on early failure of arteriovenous fistulas for hemodialysis: a randomized controlled trial. JAMA 2008, 299:2164-2171.
91. Ho PM, Peterson ED, Wang L, et al. Incidence of death and acute myocardial infarction associated with stopping clopidogrel after acute coronary syndrome. JAMA 2008, 299:532-539.
92. Ho PM, Tsai TT, Wang TY, et al. Adverse events after stopping clopidogrel in post-acute coronary syndrome patients: insights from a large integrated healthcare delivery system. Circ Cardiovasc Qual Outcomes 2010, 3:303-308.
93. Collet JP, Montalescot G, Steg PG, et al. Clinical outcomes according to permanent discontinuation of clopidogrel or placebo in the CHARISMA trial. Arch Cardiovasc Dis 2009, 102:485-496.
94. Sibbing D, Stegherr J, Braun S, et al. A double-blind, randomized study on prevention and existence of a rebound phenomenon of platelets after cessation of clopidogrel treatment. J Am Coll Cardiol 2010, 55:558-565.
95. Jakubowski JA, Li YG, Payne CD, et al. Absence of "rebound" platelet hyperreactivity following cessation of prasugrel. Thromb Haemost 2011, 106:174-176.
96. Diehl P, Halscheid C, Olivier C, et al. Discontinuation of long term clopidogrel therapy induces platelet rebound hyperaggregability between 2 and 6 weeks post cessation. Clin Res Cardiol 2011, 100:765-771.
97. Mylotte D, Peace AJ, Tedesco AT, et al. Clopidogrel discontinuation and platelet reactivity following coronary stenting. J Thromb Haemost 2011, 9:24-32.
98. Geraghty OC, Paul NL, Chandratheva A, Rothwell PM. Low risk of rebound events after a short course of clopidogrel in acute TIA or minor stroke. Neurology 2010, 74:1891-1896.
99. Frelinger AL, Barnard MR, Fox ML, Michelson AD. The platelet activity after clopidogrel termination (PACT) study. Circ Cardiovasc Interv 2010, 3:442-449.
100. Agnelli G, Prandoni P, Santamaria MG, et al. Three months versus one year of oral anticoagulant therapy for idiopathic deep venous thrombosis. Warfarin optimal duration Italian trial investigators. N Engl J Med 2001, 345:165-169.
101. Cattaneo M. New P2Y(12) inhibitors. Circulation 2010, 121:171-179.
102. Bonello L, Tantry US, Marcucci R, et al. Consensus and future directions on the definition of high on-treatment platelet reactivity to adenosine diphosphate. J Am Coll Cardiol 2010, 56:919-933.
103. Cattaneo M. Aspirin and clopidogrel: efficacy, safety, and the issue of drug resistance. Arterioscler Thromb Vasc Biol 2004, 24:1980-1987.
104. Brar SS, Ten Berg J, Marcucci R, et al. Impact of platelet reactivity on clinical outcomes after percutaneous coronary intervention. A collaborative meta-analysis of individual participant data. J Am Coll Cardiol 2011, 58:1945-1954.
105. Bates ER, Lau WC, Angiolillo DJ. Clopidogrel-drug interactions. J Am Coll Cardiol 2011, 57:1251-1263.
106. Chen M, Wei JF, Xu YN, Liu XJ, Huang DJ. A meta-analysis of impact of proton pump inhibitors on antiplatelet effect of clopidogrel. Cardiovasc Ther 2011, [Epub ahead of print].
107. Cattaneo M. Response variability to clopidogrel: is tailored treatment, based on laboratory testing, the right solution?. J Thromb Haemost 2012, 10(3):327-336.
108. Hulot JS, Collet JP, Silvain J, Pena A, et al. Cardiovascular risk in clopidogrel-treated patients according to cytochrome P450 2C19*2 loss-of-function allele or proton pump inhibitor coadministration: a systematic meta-analysis. J Am Coll Cardiol 2010, 56:134-143.
109. 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, 304:1821-1830.
110. Sofi F, Giusti B, Marcucci R, et al. Cytochrome P450 2C19*2 polymorphism and cardiovascular recurrences in patients taking clopidogrel: a meta-analysis. Pharmacogenomics J 2011, 11:199-206.
111. Bauer T, Bouman HJ, van Werkum JW, et al. Impact of CYP2C19 variant genotypes on clinical efficacy of antiplatelet treatment with clopidogrel: systematic review and meta-analysis. BMJ 2011, 343:d4588.
112. Zabalza M, Subirana I, Sala J, et al. Meta-analyses of the association between cytochrome CYP2C19 loss- and gain-of-function polymorphisms and cardiovascular outcomes in patients with coronary artery disease treated with clopidogrel. Heart 2012, 98(2):100-108.
113. 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, 306:2704-2714.
114. Paré G, Mehta SR, Yusuf S, et al. Effects of CYP2C19 genotype on outcomes of clopidogrel treatment. N Engl J Med 2010, 363:1704-1714.
115. 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, 376:1312-1319.
116. 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, 55:2427-2434.
117. 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.
118. Mega JL, Hochholzer W, Frelinger AL, et al. Dosing clopidogrel based on CYP2C19 genotype and the effect on platelet reactivity in patients with stable cardiovascular disease. JAMA 2011, 306:2221-2228.
119. Price MJ, Berger PB, Teirstein PS, et al. for the 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.
120. Parodi G, Marcucci R, Valenti R, et al. 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.
121. Sugidachi A, Asai F, Ogawa T, Inoue T, Koike H. The in vivo pharmacological profile of CS-747, a novel antiplatelet agent with platelet ADP receptor antagonist properties. Br J Pharmacol 2000, 129:1439-1446.
122. Sugidachi A, Asai F, Yoneda K, et al. Antiplatelet action of R-99224, an active metabolite of a novel thienopyridine-type G(i)-linked P2T antagonist, CS-747. Br J Pharmacol 2001, 132:47-54.
123. Niitsu Y, Jakubowski JA, Sugidachi A, Asai F. Pharmacology of CS-747 (prasugrel, LY640315), a novel, potent antiplatelet agent with in vivo P2Y12 receptor antagonist activity. Sem Thromb Hemost 2005, 31:184-194.
124. Hagihara K, Kazui M, Kurihara A, et al. Biotransformation of prasugrel, a novel thienopyridine antiplatelet agent, to the pharmacologically active metabolite. Drug Metab Dispos 2010, 38:898-904.
125. Williams ET, Jones KO, Ponsler GD, et al. The biotransformation of prasugrel, a new thienopyridine prodrug, by the human carboxylesterases 1 and 2. Drug Metab Dispos 2008, 36:1227-1232.
126. 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, 34:600-607.
127. Small DS, Li YG, Ernest CS, et al. Integrated analysis of pharmacokinetic data across multiple clinical pharmacology studies of prasugrel, a new thienopyridine antiplatelet agent. J Clin Pharmacol 2011, 51:321-332.
128. 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. Eur Heart J 2006, 27:1166-1173.
129. 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):e9-16.
130. 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, 5:2429-2436.
131. Sugidachi A, Ogawa T, Kurihara A, et al. The greater in vivo antiplatelet effects of prasugrel as compared to clopidogrel reflect more efficient generation of its active metabolite with similar antiplatelet activity to that of clopidogrel's active metabolite. J Thromb Haemost 2007, 5:1545-1551.
132. 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.
133. Wallentin L, Varenhorst C, James S, et al. Prasugrel achieves greater and faster P2Y12 receptor-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.
134. Michelson AD, Frelinger AL, Braunwald E, et al. Pharmacodynamic assessment of platelet inhibition by prasugrel vs. clopidogrel in the TRITON-TIMI 38 trial. Eur Heart J 2009, 30:1753-1763.
135. Bonello L, Pansieri M, Mancini J, et al. 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.
136. Aradi D, Kuliczkowski W, Atar D, Serebruany VL. Inter-patient variability and impact of proton pump inhibitors on platelet reactivity after prasugrel. Thromb Haemost 2012, 107(2):338-345.
137. Capranzano P, Tamburino C, Capodanno D, et al. Platelet function profiles in the elderly: results of a pharmacodynamic study in patients on clopidogrel therapy and effects of switching to prasugrel 5mg in patients with high platelet reactivity. Thromb Haemost 2011, 106:1149-1157.
138. 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, 4:403-410.
139. Alexopoulos D, Panagiotou A, Xanthopoulou I, et al. Antiplatelet effects of prasugrel vs. double clopidogrel in patients on hemodialysis and with high on-treatment platelet reactivity. J Thromb Haemost 2011, 9:2379-2385.
140. Alexopoulos D, Xanthopoulou I, Davlouros P, et al. Prasugrel overcomes high on-clopidogrel platelet reactivity in chronic coronary artery disease patients more effectively than high dose (150mg) clopidogrel. Am Heart J 2011, 162:733-739.
141. Angiolillo DJ, Badimon JJ, Saucedo JF, et al. A pharmacodynamic comparison of prasugrel vs. high-dose clopidogrel in patients with type 2 diabetes mellitus and coronary artery disease: results of the optimizing anti-platelet therapy in diabetes MellitUS (OPTIMUS)-3 trial. Eur Heart J 2011, 32:838-846.
142. Montalescot G, Sideris G, Cohen R, et al. Prasugrel compared with high-dose clopidogrel in acute coronary syndrome. The randomised, double-blind ACAPULCO study. Thromb Haemost 2010, 103:213-223.
143. Pena A, Collet JP, Hulot JS, et al. Can we override clopidogrel resistance?. Circulation 2009, 119:2854-2857.
144. 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, 119:2553-2560.
145. Varenhorst C, James S, Erlinge D, et al. Genetic variation of CYP2C19 affects both pharmacokinetic and pharmacodynamic responses to clopidogrel but not prasugrel in aspirin-treated patients with coronary artery disease. Eur Heart J 2009, 30:1744-1752.
146. Small DS, Farid NA, Payne CD, et al. Effect of intrinsic and extrinsic factors on the clinical pharmacokinetics and pharmacodynamics of prasugrel. Clin Pharmacokinet 2010, 49:777-798.
147. Jakubowski JA, Riesmeyer JS, Close SL, et al. TRITON and beyond: new insights into the profile of prasugrel. Cardiovasc Ther 2011, Feb:17. [Epub ahead of print].
148. Wiviott SD, Antman EM, Winters KJ, et al. Randomized comparison of prasugrel (CS-747, LY640315), a novel thienopyridine P2Y12 antagonist, with clopidogrel in percutaneous coronary intervention: results of the joint utilization of medications to block platelets optimally (JUMBO)-TIMI 26 trial. Circulation 2005, 111:3366-3373.
149. 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, 116:2923-2932.
150. 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.
151. Antman EM, Wiviott SD, Murphy SA, et al. Early and late benefits of prasugrel in patients with acute coronary syndromes undergoing percutaneous coronary intervention: a TRITON-TIMI 38 (TRial to assess improvement in therapeutic outcomes by optimizing platelet inhibition with Prasugrel-thrombolysis in myocardial infarction) analysis. J Am Coll Cardiol 2008, 51:2028-2033.
152. Morrow DA, Wiviott SD, White HD, et al. Effect of the novel thienopyridine prasugrel compared with clopidogrel on spontaneous and procedural myocardial infarction in the trial to assess improvement in therapeutic outcomes by optimizing platelet inhibition with Prasugrel-thrombolysis in myocardial infarction 38: an application of the classification system from the universal definition of myocardial infarction. Circulation 2009, 119:2758-2764.
153. Wiviott SD, Braunwald E, Angiolillo DJ, et al. Greater clinical benefit of more intensive oral antiplatelet therapy with prasugrel in patients with diabetes mellitus in the trial to assess improvement in therapeutic outcomes by optimizing platelet inhibition with prasugrel-thrombolysis in myocardial infarction 38. Circulation 2008, 118:1626-1636.
154. Montalescot G, Wiviott SD, Braunwald E, et al. Prasugrel compared with clopidogrel in patients undergoing percutaneous coronary intervention for ST-elevation myocardial infarction (TRITON-TIMI 38): double-blind, randomised controlled trial. Lancet 2009, 373:723-731.
155. Wiviott SD, Braunwald E, McCabe CH, et al. Intensive oral antiplatelet therapy for reduction of ischaemic events including stent thrombosis in patients with acute coronary syndromes treated with percutaneous coronary intervention and stenting in the TRITON-TIMI 38 trial: a subanalysis of a randomised trial. Lancet 2008, 371:1353-1363.
156. Murphy SA, Antman EM, Wiviott SD, et al. Reduction in recurrent cardiovascular events with prasugrel compared with clopidogrel in patients with acute coronary syndromes from the TRITON-TIMI 38 trial. Eur Heart J 2008, 29:2473-2479.
157. Ajani AE, Lefkovits J. Approaching an age of reason with antiplatelet therapy. Lancet 2008, 371:1315-1316.
158. Bonello L, Camoin-Jau L, Armero S, et al. Tailored clopidogrel loading
159. Sibbing D, Braun S, Morath T, et al. Platelet reactivity after clopidogrel treatment assessed with point-of-care analysis and early drug-eluting stent thrombosis. J Am Coll Cardiol 2009, 53:849-856.
160. Payne CD, Li YG, Brandt JT, et al. Switching directly to prasugrel from clopidogrel results in greater inhibition of platelet aggregation in aspirin-treated subjects. Platelets 2008, 19:275-281.
161. Angiolillo DJ, Saucedo JF, Deraad R, et al. Increased platelet inhibition after switching from maintenance clopidogrel to prasugrel in patients with acute coronary syndromes: results of the SWAP (SWitching Anti Platelet) study. J Am Coll Cardiol 2010, 56:1017-1023.
162. van Giezen JJJ, Humphries RG. Preclinical and clinical studies with selective reversible direct P2Y12 antagonists. Sem Thromb Hemost 2005, 31:195-204.
163. Nilsson L, van Giezen JJJ, Greasley PJ.Evidence for distinct ligand binding sites on recombinant human P2Y12 receptors circulation. 2006; 114: II_248-II_249 (abs.).
164. van Giezen JJ, Nilsson L, Berntsson P, et al. Ticagrelor binds to the human P2Y receptor independently from ADP but antagonizes ADP-induced receptor signaling and platelet aggregation. J Thromb Haemost 2009, 7:1556-1565.
165. 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.
166. 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, 120:2577-2585.
167. Storey RF, Angiolillo DJ, Patil SB, et al. Inhibitory effects of ticagrelor compared with clopidogrel on platelet function in patients with acute coronary syndromes: the PLATO (PLATelet inhibition and patient outcomes) PLATELET substudy. J Am Coll Cardiol 2010, 56:1456-1462.
168. Gurbel PA, Bliden KP, Butler K, et al. Response to ticagrelor in clopidogrel nonresponders and responders and effect of switching therapies: the RESPOND study. Circulation 2010, 121:1188-1199.
169. Teng R, Oliver S, Hayes MA, Butler K. Absorption, distribution, metabolism, and excretion of ticagrelor in healthy subjects. Drug Metab Dispos 2010, 38:1514-1521.
170. 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, 3:556-566.
171. Bjorkman J-A, Kirk I, van Giezen JI. AZD6140 inhibits adenosine uptake into erythrocytes and enhances coronary blood flow after local ischemia or intracoronary adenosine infusion. Circulation 2007, 116. II_28-c (abstract 245).
172. Wang K, Zhou X, Huang Y, et al. Adjunctive treatment with ticagrelor, but not clopidogrel, added to tPA enables sustained coronary artery recanalisation with recovery of myocardium perfusion in a canine coronary thrombosis model. Thromb Haemost 2010, 104:609-617.
173. Cannon CP, Husted S, Harrington RA, et al. Safety, tolerability, and initial efficacy of AZD6140, the first reversible oral adenosine diphosphate receptor antagonist, compared with clopidogrel, in patients with non-ST-segment elevation acute coronary syndrome: primary results of the DISPERSE-2 trial. J Am Coll Cardiol 2007, 50:1844-1851.
174. Serebruany VL, Stebbing J, Atar D. Dyspnea after antiplatelet agents: the AZD6140 controversy. Int J Clin Pract 2007, 61:529-533.
175. Storey RF, Bliden KP, Patil SB, et al. Incidence of dyspnea and assessment of cardiac and pulmonary function in patients with stable coronary artery disease receiving ticagrelor, clopidogrel, or placebo in the ONSET/OFFSET study. J Am Coll Cardiol 2010, 56:185-193.
176. Storey RF, Husted S, Harrington RA, et al. Inhibition of platelet aggregation by AZD6140, a reversible oral P2Y12 receptor antagonist, compared with clopidogrel in patients with acute coronary syndromes. J Am Coll Cardiol 2007, 50:1852-1856.
177. Wallentin L, Becker RC, Budaj A, et al. Ticagrelor versus clopidogrel in patients with acute coronary syndromes. N Engl J Med 2009, 361:1045-1057.
178. Becker RC, Bassand JP, Budaj A, et al. Bleeding complications with the P2Y12 receptor antagonists clopidogrel and ticagrelor in the PLATelet inhibition and patient outcomes (PLATO) trial. Eur Heart J 2011, 32:2933-2944.
179. Held C, Asenblad N, Bassand JP, et al. Ticagrelor versus clopidogrel in patients with acute coronary syndromes undergoing coronary artery bypass surgery: results from the PLATO (platelet inhibition and patient outcomes) trial. J Am Coll Cardiol 2011, 57:672-684.
180. Cannon CP, Harrington RA, James S, et al. Comparison of ticagrelor with clopidogrel in patients with a planned invasive strategy for acute coronary syndromes (PLATO): a randomised double-blind study. Lancet 2010, 375:283-293.
181. James S, Angiolillo DJ, Cornel JH, et al. Ticagrelor vs. Clopidogrel in patients with acute coronary syndromes and diabetes: a substudy from the PLATelet inhibition and patient outcomes trial. Eur Heart J 2010, 31:3006-3016.
182. Armstrong PW, Siha H, Fu Y, et al. ST elevation acute coronary syndromes in the the platelet inhibition and patient outcomes (PLATO) trial: insights from the ECG substudy. Circulation 2012, 125(3):514-521.
183. James S, Budaj A, Aylward P, et al. Ticagrelor versus clopidogrel in acute coronary syndromes in relation to renal function: results from the platelet inhibition and patient outcomes (PLATO) trial. Circulation 2010, 122:1056-1067.
184. 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, 376:1320-1328.
185. Mahaffey KW, Wojdyla DM, Carroll K, et al. Ticagrelor compared with clopidogrel by geographic region in the platelet inhibition and patient outcomes (PLATO) trial. Circulation 2011, 124:544-554.
186. Scirica BM, Cannon CP, Emanuelsson H, et al. The incidence of bradyarrhythmias and clinical bradyarrhythmic events in patients with acute coronary syndromes treated with ticagrelor or clopidogrel in the PLATO (platelet inhibition and patient outcomes) trial: results of the continuous electrocardiographic assessment substudy. J Am Coll Cardiol 2011, 57:1908-1916.
187. Marteau F, Le Poul E, Communi D, Labouret C, et al. Pharmacological characterization of the human P2Y13 receptor. Mol Pharmacol 2003, 64:104-112.
188. Fumagalli M, Trincavelli L, Lecca D, et al. Cloning, pharmacological characterization and distribution of the rat G-protein-coupled P2Y(13) receptor. Biochem Pharmacol 2004, 68:113-124.
189. Srinivasan S, Mir F, Huang JS, et al. The P2Y12 antagonists, 2-methylthioadenosine 5′-monophosphate triethylammonium salt and cangrelor (ARC69931MX), can inhibit human platelet aggregation through a Gi-independent increase in cAMP levels. J Biol Chem 2009, 284:16108-16117.
190. Storey RF, Oldroyd KG, Wilcox RG. Open multicentre study of the P2T receptor antagonist AR-C69931MX assessing safety, tolerability and activity in patients with acute coronary syndromes. Thromb Haemost 2001, 85:401-407.
191. Storey RF, Wilcox RG, Heptinstall S. Comparison of the pharmacodynamic effects of the platelet ADP receptor antagonists clopidogrel and AR-C69931MX in patients with ischaemic heart disease. Platelets 2002, 13:407-413.
192. Beham M, Fox S, Sanderson H, et al. Effect of clopidogrel on procoagulant activity in acute coronary syndromes: evidence for incomplete P2Y12 receptor blockade. Circulation 2002, 106:II-149-II-150.
193. Jacobsson F, Swahn E, Wallentin L, Ellborg M. Safety profile and tolerability of intravenous ARC69931MX, a new antiplatelet drug, in unstable angina pectoris and non-Q-wave myocardial infarction. Clin Ther 2002, 24:752-765.
194. Greenbaum AB, Grines CL, Bittl JA, et al. Initial experience with an intravenous P2Y12 platelet receptor antagonist in patients undergoing percutaneous coronary intervention: results from a 2-part, phase II, multicenter, randomized, placebo- and active-controlled trial. Am Heart J 2006, 151:689.e1-689.e10.
195. Steinhubl SR, Oh JJ, Oestreich JH, et al. Transitioning patients from cangrelor to clopidogrel: pharmacodynamic evidence of a competitive effect. Thromb Res 2008, 121:527-534.
196. Dovlatova NL, Jakubowski JA, Sugidachi A, Heptinstall S. Competition between reversible and irreversible P2Y12 antagonists and its influence on ADP-mediated platelet activation. J Thromb Hemost 2008, 6:1153-1159.
197. Greenbaum AB, Ohman EM, Gibson CM, et al. Preliminary experience with intravenous P2Y12 platelet receptor inhibition as an adjunct to reduced-dose alteplase during acute myocardial infarction: results of the safety, tolerability and effect on patency in acute myocardial infarction (STEP-AMI) angiographic trial. Am Heart J 2007, 154:702-709.
198. Harrington RA, Stone GW, McNulty S, et al. Platelet inhibition with cangrelor in patients undergoing PCI. N Engl J Med 2009, 361:2318-2329.
199. Bhatt DL, Lincoff AM, Gibson CM, et al. Intravenous platelet blockade with cangrelor during PCI. N Engl J Med 2009, 361:2330-2341.
200. Angiolillo DJ, Firstenberg MS, Price MJ, et al. Bridging antiplatelet therapy with cangrelor in patients undergoing cardiac surgery: a randomized controlled trial. JAMA 2012, 307:265-274.
201. Haberstock-Debic H, Andre P, Mills S, et al. A clopidogrel-insensitive inducible pool of P2Y12 receptors contributes to thrombus formation: inhibition by elinogrel, a direct-acting, reversible P2Y12 antagonist. J Pharmacol Exp Ther 2011, 339:54-61.
202. André P, DeGuzman F, Haberstock-Debic H, et al. Thienopyridines, but not elinogrel, result in off-target effects at the vessel wall that contribute to bleeding. J Pharmacol Exp Ther 2011, 338:22-30.
203. 12 inhibitor for IV and oral use. J Am Coll Cardiol 2007, 49:326A.
204. Lieu HD C P, Andre P, Leese PT, et al. Initial intravenous experience with PRT060128 (PRT128), an orally-available, direct-acting, and reversible P2Y12 inhibitor. J Thromb Haemost 2007, 5(Suppl. 2). P-T-292.
205. Conley P, Stephens G, He M, et al. A novel pharmacodynamic perfusion chamber assay reveals superior and unique antithrombotic activities of a direct-acting P2Y12 antagonist, PRT128, relative to clopidogrel. Blood 2006, 108:900. (abs).
206. Gurbel PA, Bliden KP, Antonino MJ, et al. The effect of elinogrel on high platelet reactivity during dual antiplatelet therapy and the relation to CYP2C19*2 genotype: first experience in patients. J Thromb Haemost 2010, 8:43-53.
207. Berger JS, Roe MT, Gibson CM, et al. Safety and feasibility of adjunctive antiplatelet therapy with intravenous elinogrel, a direct-acting and reversible P2Y12 ADP-receptor antagonist, before primary percutaneous intervention in patients with ST-elevation myocardial infarction: the Early Rapid ReversAl of platelet thromboSis with intravenous Elinogrel before PCI to optimize reperfusion in acute myocardial infarction (ERASE MI) pilot trial. Am Heart J 2009, 158:998-1004.
208. Leonardi S, Rao SV, Harrington RA, et al. Rationale and design of the randomized, double-blind trial testing INtraveNous and oral administration of elinogrel, a selective and reversible P2Y(12)-receptor inhibitor, versus clopidogrel to eVAluate tolerability and efficacy in nonurgent percutaneous coronary interventions patients (INNOVATE-PCI). Am Heart J 2010, 160:65-72.
209. Rao SV. INNOVATE-PCI: a phase II safety and efficacy study of PRT060128 (elinogrel), a novel intravenous and oral P2Y12 inhibitor, in non-urgent PCI (abstract 2036). 2010 ESC Congress. 2010.