Pharmacology of the new P2Y12 receptor inhibitors: Insights on pharmacokinetic and pharmacodynamic properties

Drugs

Volumn 73, Issue 15, 2013, Pages 1681-1709

  Ferri, Nicola ^a   Corsini, Alberto ^a   Bellosta, Stefano ^a  

^a UNIVERSITY OF MILAN   (Italy)

Author keywords

[No Author keywords available]

Indexed keywords

ACETYLSALICYLIC ACID; AMIODARONE; ANTICOAGULANT AGENT; ATORVASTATIN; CANGRELOR; CARBAMAZEPINE; CIMETIDINE; CLOPIDOGREL; ERYTHROMYCIN; ETRAVIRINE; FELBAMATE; FLUCONAZOLE; FLUOXETINE; FLUVOXAMINE; KETOCONAZOLE; LANSOPRAZOLE; OMEPRAZOLE; OXANDROLONE; PANTOPRAZOLE; PRASUGREL; PURINERGIC P2Y12 RECEPTOR INHIBITOR; RABEPRAZOLE; RIFAMPICIN; SIMVASTATIN; SULFAPHENAZOLE; TICAGRELOR; UNCLASSIFIED DRUG; UNINDEXED DRUG; VERAPAMIL; VORICONAZOLE; FIBRINOLYTIC AGENT; P2RY12 PROTEIN, HUMAN; PURINERGIC P2Y RECEPTOR ANTAGONIST; PURINERGIC P2Y12 RECEPTOR;

ANTICOAGULATION; AREA UNDER THE CURVE; ATHEROSCLEROSIS; BLEEDING TIME; CHRONIC KIDNEY DISEASE; CONTINUOUS INFUSION; DIABETES MELLITUS; DIABETIC PATIENT; DOSE RESPONSE; DRUG ABSORPTION; DRUG BIOAVAILABILITY; DRUG BLOOD LEVEL; DRUG CLEARANCE; DRUG ELIMINATION; DRUG HALF LIFE; DRUG POTENCY; DRUG PROTEIN BINDING; DRUG RESPONSE; FECES; GASTROINTESTINAL ABSORPTION; HUMAN; IC 50; LOADING DRUG DOSE; MAINTENANCE THERAPY; MAXIMUM PLASMA CONCENTRATION; NONHUMAN; PLASMA CONCENTRATION-TIME CURVE; REVIEW; STEADY STATE; THROMBOCYTE AGGREGATION; THROMBOCYTE FUNCTION; THROMBOCYTE MEMBRANE; THROMBOCYTE RELEASE REACTION; TIME TO MAXIMUM PLASMA CONCENTRATION; URINARY EXCRETION; ANIMAL; DRUG EFFECT; DRUG INTERACTION; METABOLISM; METHODOLOGY; MOLECULARLY TARGETED THERAPY;

ANIMALS; DRUG INTERACTIONS; FIBRINOLYTIC AGENTS; HUMANS; MOLECULAR TARGETED THERAPY; PLATELET AGGREGATION; PURINERGIC P2Y RECEPTOR ANTAGONISTS; RECEPTORS, PURINERGIC P2Y12;

EID: 84887222370     PISSN: 00126667     EISSN: 11791950     Source Type: Journal    
DOI: 10.1007/s40265-013-0126-z     Document Type: Review

References (201)

1. Jennings LK. Mechanisms of platelet activation: need for new strategies to protect against platelet-mediated atherothrombosis. Thromb Haemost. 2009;102(2):248-57.
2. Steinhubl SR, Moliterno DJ. The role of the platelet in the pathogenesis of atherothrombosis. Am J Cardiovasc Drugs. 2005;5(6):399-408. (Pubitemid 41584840)
3. Levine GN, Bates ER, Blankenship JC, et al. 2011 ACCF/AHA/SCAI Guideline for Percutaneous Coronary Intervention: executive summary: 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):2574-609.
4. 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. (Pubitemid 32758501)
5. Angiolillo DJ, Capranzano P. Pharmacology of emerging novel platelet inhibitors. Am Heart J. 2008;156(2 Suppl):S10-5.
6. Wijns W, Kolh P, Danchin N, et al. Guidelines on myocardial revascularization. Eur Heart J. 2010;31(20):2501-55.
7. Gurbel PA, Bliden KP, Hiatt BL, et al. Clopidogrel for coronary stenting: response variability, drug resistance, and the effect of pretreatment platelet reactivity. Circulation. 2003;107(23):2908-13. (Pubitemid 36736631)
8. Kushner FG, Hand M, Smith SC Jr, et al. 2009 focused updates: ACC/AHA guidelines for the management of patients with ST-elevation myocardial infarction (updating the 2004 guideline and 2007 focused update) and ACC/AHA/SCAI guidelines on percutaneous coronary intervention (updating the 2005 guideline and 2007 focused update) a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2009;54(23):2205-41.
9. Burnstock G. Purinergic signaling and vascular cell proliferation and death. Arterioscler Thromb Vasc Biol. 2002;22(3):364-73. (Pubitemid 34218740)
10. Evans AM, Wyatt CN, Kinnear NP, et al. Pyridine nucleotides and calcium signalling in arterial smooth muscle: from cell physiology to pharmacology. Pharmacol Ther. 2005;107(3):286-313. (Pubitemid 41178973)
11. Kunapuli SP, Daniel JL. P2 receptor subtypes in the cardiovascular system. Biochem J. 1998; 336 (Pt 3):513-23.
12. Born GV. Adenosine diphosphate as a mediator of platelet aggregation in vivo: an editorial view. Circulation. 1985;72(4):741-6. (Pubitemid 16245183)
13. Gachet C. P2Y(12) receptors in platelets and other hematopoietic and non-hematopoietic cells. Purinergic Signal. 2012;8(3):609-19.
14. Fredholm BB, Abbracchio MP, Burnstock G, et al. Nomenclature and classification of purinoceptors. Pharmacol Rev. 1994;46(2):143-56. (Pubitemid 24984777)
15. Burnstock G. Purine and pyrimidine receptors. Cell Mol Life Sci. 2007;64(12):1471-83. (Pubitemid 46954150)
16. Harden TK, Sesma JI, Fricks IP, et al. Signalling and pharmacological properties of the P2Y receptor. Acta Physiol (Oxf). 2010;199(2):149-60.
17. Hollopeter G, Jantzen HM, Vincent D, et al. Identification of the platelet ADP receptor targeted by antithrombotic drugs. Nature. 2001;409(6817):202-7. (Pubitemid 32144286)
18. Wihlborg AK, Wang L, Braun OO, et al. ADP receptor P2Y12 is expressed in vascular smooth muscle cells and stimulates contraction in human blood vessels. Arterioscler Thromb Vasc Biol. 2004;24(10):1810-5. (Pubitemid 39350296)
19. Hechler B, Leon C, Vial C, et al. The P2Y1 receptor is necessary for adenosine 5'-diphosphate-induced platelet aggregation. Blood. 1998;92(1):152-9. (Pubitemid 28303187)
20. Leon C, Hechler B, Freund M, et al. Defective platelet aggregation and increased resistance to thrombosis in purinergic P2Y(1) receptor-null mice. J Clin Invest. 1999;104(12):1731-7. (Pubitemid 30053190)
21. Gachet C. Regulation of platelet functions by P2 receptors. Annu Rev Pharmacol Toxicol. 2006;46:277-300. (Pubitemid 43271191)
22. Conley PB, Delaney SM. Scientific and therapeutic insights into the role of the platelet P2Y12 receptor in thrombosis. Curr Opin Hematol. 2003;10(5):333-8. (Pubitemid 36936603)
23. Cattaneo M, Lecchi A, Lombardi R, et al. Platelets from a patient heterozygous for the defect of P2CYC receptors for ADP have a secretion defect despite normal thromboxane A2 production and normal granule stores: further evidence that some cases of platelet 'primary secretion defect' are heterozygous for a defect of P2CYC receptors. Arterioscler Thromb Vasc Biol. 2000;20(11):E101-6.
24. Dangelmaier C, Jin J, Smith JB, et al. Potentiation of thromboxane A2-induced platelet secretion by Gi signaling through the phosphoinositide-3 kinase pathway. Thromb Haemost. 2001;85(2):341-8. (Pubitemid 32140582)
25. Kauffenstein G, Bergmeier W, Eckly A, et al. The P2Y(12) receptor induces platelet aggregation through weak activation of the alpha(IIb)beta(3) integrin - a phosphoinositide 3-kinase-dependent mechanism. FEBS Lett. 2001;505(2):281-90. (Pubitemid 32896681)
26. Savi P, Pflieger AM, Herbert JM. cAMP is not an important messenger for ADP-induced platelet aggregation. Blood Coagul Fibrinolysis. 1996;7(2):249-52. (Pubitemid 26167952)
27. Jackson SP, Yap CL, Anderson KE. Phosphoinositide 3-kinases and the regulation of platelet function. Biochem Soc Trans. 2004;32(Pt 2):387-92. (Pubitemid 38582133)
28. Garcia A, Kim S, Bhavaraju K, et al. Role of phosphoinositide 3-kinase beta in platelet aggregation and thromboxane A2 generation mediated by Gi signalling pathways. Biochem J. 2010;429(2):369-77.
29. Jin J, Kunapuli SP. Coactivation of two different G protein-coupled receptors is essential for ADP-induced platelet aggregation. Proc Natl Acad Sci USA. 1998;95(14):8070-4. (Pubitemid 28326067)
30. Hechler B, Eckly A, Ohlmann P, et al. The P2Y1 receptor, necessary but not sufficient to support full ADP-induced platelet aggregation, is not the target of the drug clopidogrel. Br J Haematol. 1998;103(3):858-66. (Pubitemid 28545331)
31. Savi P, Beauverger P, Labouret C, et al. Role of P2Y1 purinoceptor in ADP-induced platelet activation. FEBS Lett. 1998;422(3):291-5. (Pubitemid 28075481)
32. Nylander S, Mattsson C, Ramstrom S, et al. Synergistic action between inhibition of P2Y12/P2Y1 and P2Y12/thrombin in ADP- and thrombin-induced human platelet activation. Br J Pharmacol. 2004;142(8):1325-31. (Pubitemid 39178886)
33. Mahaut-Smith MP, Tolhurst G, Evans RJ. Emerging roles for P2X1 receptors in platelet activation. Platelets. 2004;15(3):131-44. (Pubitemid 38651025)
34. Rolf MG, Brearley CA, Mahaut-Smith MP. Platelet shape change evoked by selective activation of P2X1 purinoceptors with alpha, beta-methylene ATP. Thromb Haemost. 2001;85(2):303-8. (Pubitemid 32140576)
35. Savi P, Pereillo JM, Uzabiaga MF, et al. Identification and biological activity of the active metabolite of clopidogrel. Thromb Haemost. 2000;84(5):891-6.
36. Ito MK, Smith AR, Lee ML. Ticlopidine: a new platelet aggregation inhibitor. Clin Pharm. 1992;11(7):603-17.
37. Hasegawa M, Sugidachi A, Ogawa T, et al. Stereoselective inhibition of human platelet aggregation by R-138727, the active metabolite of CS-747 (prasugrel, LY640315), a novel P2Y12 receptor inhibitor. Thromb Haemost. 2005;94(3):593-8. (Pubitemid 41300857)
38. Ding Z, Bynagari YS, Mada SR, et al. Studies on the role of the extracellular cysteines and oligomeric structures of the P2Y12 receptor when interacting with antagonists. J Thromb Haemost. 2009;7(1):232-4.
39. Algaier I, Jakubowski JA, Asai F, et al. Interaction of the active metabolite of prasugrel, R-138727, with cysteine 97 and cysteine 175 of the human P2Y12 receptor. J Thromb Haemost. 2008;6(11):1908-14.
40. Niitsu Y, Jakubowski JA, Sugidachi A, et al. Pharmacology of CS-747 (prasugrel, LY640315), a novel, potent antiplatelet agent with in vivo P2Y12 receptor antagonist activity. Semin Thromb Hemost. 2005;31(2):184-94. (Pubitemid 40605193)
41. Sugidachi A, Asai F, Ogawa T, et al. The in vivo pharmacological profile of CS-747, a novel antiplatelet agent with platelet ADP receptor antagonist properties. Br J Pharmacol. 2000;129(7):1439-46. (Pubitemid 30175717)
42. Husted S, van Giezen JJ. Ticagrelor: the first reversibly binding oral P2Y12 receptor antagonist. Cardiovasc Ther. 2009;27(4):259-74.
43. Yoneda K, Iwamura R, Kishi H, et al. Identification of the active metabolite of ticlopidine from rat in vitro metabolites. Br J Pharmacol. 2004;142(3):551-7. (Pubitemid 38869869)
44. Humphries RG, Robertson MJ, Leff P. A novel series of P2T purinoceptor antagonists: definition of the role of ADP in arterial thrombosis. Trends Pharmacol Sci. 1995;16(6):179-81.
45. Cattabeni F, Williams M. Purines 2000: Third International Symposium on Nucleosides and Nucleotides. 9-13 July 2000, Madrid, Spain. IDrugs. 2000;3(10):1182-4.
46. Chattaraj SC. Cangrelor AstraZeneca. Curr Opin Investig Drugs. 2001;2(2):250-5. (Pubitemid 32185951)
47. Springthorpe B, Bailey A, Barton P, et al. From ATP to AZD6140: the discovery of an orally active reversible P2Y12 receptor antagonist for the prevention of thrombosis. Bioorg Med Chem Lett. 2007;17(21):6013-8. (Pubitemid 47446193)
48. Wang K, Zhou X, Zhou Z, et al. Sustained coronary artery recanalization with adjunctive infusion of a novel P2T-receptor antagonist AR-C69931 in a canine model [abstract 1111-47]. J Am Coll Cardiol. 2000;35(Suppl.):281A-282A.
49. Huang J, Driscoll EM, Gonzales ML, et al. Prevention of arterial thrombosis by intravenously administered platelet P2T receptor antagonist AR-C69931MX in a canine model. J Pharmacol Exp Ther. 2000;295(2):492-9.
50. 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):2577-85.
51. van Giezen JJ, Humphries RG. Preclinical and clinical studies with selective reversible direct P2Y12 antagonists. Semin Thromb Hemost. 2005;31(2):195-204. (Pubitemid 40605194)
52. Van Giezen JJ, Zachrisson H, Bjorkman JA. Reduced bleeding time prolongation for the reversible P2Y12 antagonist AZD6140 compared with clopidogrel and AZ11703072, a chemical compound indistinguishable from prasugrel, in both a rat and a dog model of combined thrombosis and hemostasis. Arterioscler Thromb Cardiovasc Dis. 2008;28:e40.
53. Wiviott SD, Antman EM, Gibson CM, et al. Evaluation of prasugrel compared with clopidogrel in patients with acute coronary syndromes: design and rationale for the TRial to assess Improvement in Therapeutic Outcomes by optimizing platelet InhibitioN with prasugrel Thrombolysis In Myocardial Infarction 38 (TRITON-TIMI 38). Am Heart J. 2006;152(4):627-35. (Pubitemid 44396884)
54. Wallentin L, Becker RC, Budaj A, et al. Ticagrelor versus clopidogrel in patients with acute coronary syndromes. N Engl J Med. 2009;361(11):1045-57.
55. 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(14):1744-52.
56. Kazui M, Nishiya Y, Ishizuka T, et al. 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. 2010;38(1):92-9.
57. Floyd CN, Passacquale G, Ferro A. Comparative pharmacokinetics and pharmacodynamics of platelet adenosine diphosphate receptor antagonists and their clinical implications. Clin Pharmacokinet. 2012;51(7):429-42.
58. Small DS, Wrishko RE, Ernest CS 2nd, et al. Prasugrel pharmacokinetics and pharmacodynamics in subjects with moderate renal impairment and end-stage renal disease. J Clin Pharm Ther. 2009;34(5):585-94.
59. Farid NA, Small DS, Payne CD, et al. Effect of atorvastatin on the pharmacokinetics and pharmacodynamics of prasugrel and clopidogrel in healthy subjects. Pharmacotherapy. 2008;28(12):1483-94.
60. Asai F, Jakubowski JA, Naganuma H, et al. Platelet inhibitory activity and pharmacokinetics of prasugrel (CS-747) a novel thienopyridine P2Y12 inhibitor: a single ascending dose study in healthy humans. Platelets. 2006;17(4):209-17. (Pubitemid 43890792)
61. Ernest CS 2nd, Small DS, Rohatagi S, et al. Population pharmacokinetics and pharmacodynamics of prasugrel and clopidogrel in aspirin-treated patients with stable coronary artery disease. J Pharmacokinet Pharmacodyn. 2008;35(6):593-618.
62. von Beckerath N, Taubert D, Pogatsa-Murray G, et al. Absorption, metabolization, and antiplatelet effects of 300-, 600-, and 900-mg loading doses of clopidogrel: results of the ISAR-CHOICE (Intracoronary Stenting and Antithrombotic Regimen: Choose between 3 High Oral Doses for Immediate Clopidogrel Effect) Trial. Circulation. 2005;112(19):2946-50. (Pubitemid 41612296)
63. Taubert D, von Beckerath N, Grimberg G, et al. Impact of P-glycoprotein on clopidogrel absorption. Clin Pharmacol Ther. 2006;80(5):486-501. (Pubitemid 44767878)
64. Cairns JA, Eikelboom J. Clopidogrel resistance: more grist for the mill. J Am Coll Cardiol. 2008;51(20):1935-7.
65. 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):1312-9.
66. 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):357-74. (Pubitemid 350233359)
67. 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(2):126-42.
68. 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):600-7.
69. 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):2553-60.
70. Wallentin L. P2Y(12) inhibitors: differences in properties and mechanisms of action and potential consequences for clinical use. Eur Heart J. 2009;30(16):1964-77.
71. Teng R, Oliver S, Hayes MA, et al. Absorption, distribution, metabolism, and excretion of ticagrelor in healthy subjects. Drug Metab Dispos. 2010;38(9):1514-21.
72. Teng R. Pharmacokinetic, pharmacodynamic and pharmacogenetic profile of the oral antiplatelet agent ticagrelor. Clin Pharmacokinet. 2012;51(5):305-18.
73. Storey RF. Melissa Thornton S, Lawrance R, et al. Ticagrelor yields consistent dose-dependent inhibition of ADP-induced platelet aggregation in patients with atherosclerotic disease regardless of genotypic variations in P2RY12, P2RY1, and ITGB3. Platelets. 2009;20(5):341-8.
74. 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):1320-8.
75. Angiolillo DJ, Bhatt DL, Gurbel PA, et al. Advances in antiplatelet therapy: agents in clinical development. Am J Cardiol. 2009;103(3 Suppl):40A-51A.
76. Akers WS, Oh JJ, Oestreich JH, et al. Pharmacokinetics and pharmacodynamics of a bolus and infusion of cangrelor: a direct, parenteral P2Y12 receptor antagonist. J Clin Pharmacol. 2010;50(1):27-35.
77. Frelinger AL 3rd, Bhatt DL, Lee RD, et al. Clopidogrel pharmacokinetics and pharmacodynamics vary widely despite exclusion or control of polymorphisms (CYP2C19, ABCB1, PON1), noncompliance, diet, smoking, co-medications (including proton pump inhibitors), and pre-existent variability in platelet function. J Am Coll Cardiol. 2013;61(8):872-9.
78. 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(12):919-33.
79. Bellemain-Appaix A, O'Connor SA, Silvain J, et al. Association of clopidogrel pretreatment with mortality, cardiovascular events, and major bleeding among patients undergoing percutaneous coronary intervention: a systematic review and meta-analysis. JAMA. 2012;308(23):2507-16.
80. Hochholzer W, Trenk D, Mega JL, et al. Impact of smoking on antiplatelet effect of clopidogrel and prasugrel after loading dose and on maintenance therapy. Am Heart J. 2011;162(3):518-26.e5.
81. Gurbel PA, Bliden KP, Logan DK, et al. The influence of smoking status on the pharmacokinetics and pharmacodynamics of clopidogrel and prasugrel: the PARADOX study. J Am Coll Cardiol. 2013;62(6):505-12.
82. 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(1):66.e9-16.
83. 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):2923-32. (Pubitemid 350291199)
84. Cheng JW. Ticagrelor: oral reversible P2Y(12) receptor antagonist for the management of acute coronary syndromes. Clin Ther. 2012;34(6):1209-20.
85. 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(12):777-98.
86. Teng R, Butler K. Pharmacokinetics, pharmacodynamics, tolerability and safety of single ascending doses of ticagrelor, a reversibly binding oral P2Y(12) receptor antagonist, in healthy subjects. Eur J Clin Pharmacol. 2010;66(5):487-96.
87. Parodi G, Valenti R, Bellandi B, et al. Comparison of prasugrel and ticagrelor loading doses in ST-segment elevation myocardial infarction patients. J Am Coll Cardiol. 2013;61(15):1601-6.
88. Alexopoulos D, Xanthopoulou I, Gkizas V, et al. Randomized assessment of ticagrelor versus prasugrel antiplatelet effects in patients with ST-segment-elevation myocardial infarction. Circ Cardiovasc Interv. 2012;5(6):797-804.
89. 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):363-75.
90. Cornel JH, Becker RC, Goodman SG, et al. Prior smoking status, clinical outcomes, and the comparison of ticagrelor with clopidogrel in acute coronary syndromes-insights from the PLATelet inhibition and patient Outcomes (PLATO) trial. Am Heart J. 2012;164(3):334-42.e1.
91. 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(3):265-74.
92. Bhatt DL, Stone GW, Mahaffey KW, et al. Effect of platelet inhibition with cangrelor during PCI on ischemic events. N Engl J Med. 2013;368(14):1303- 13.
93. Steinhubl SR, Oh JJ, Oestreich JH, et al. Transitioning patients from cangrelor to clopidogrel: pharmacodynamic evidence of a competitive effect. Thromb Res. 2008;121(4):527-34. (Pubitemid 351174272)
94. 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(7):407-13. (Pubitemid 35346941)
95. Donahoe SM, Stewart GC, McCabe CH, et al. Diabetes and mortality following acute coronary syndromes. JAMA. 2007;298(7):765-75. (Pubitemid 47263159)
96. Basra SS, Tsai P, Lakkis NM. Safety and efficacy of antiplatelet and antithrombotic therapy in acute coronary syndrome patients with chronic kidney disease. J Am Coll Cardiol. 2011;58(22):2263-9.
97. Mehran R, Pocock S, Nikolsky E, et al. Impact of bleeding on mortality after percutaneous coronary intervention results from a patient-level pooled analysis of the REPLACE-2 (randomized evaluation of PCI linking angiomax to reduced clinical events), ACUITY (acute catheterization and urgent intervention triage strategy), and HORIZONS-AMI (harmonizing outcomes with revascularization and stents in acute myocardial infarction) trials. JACC Cardiovasc Interv. 2011;4(6):654-64.
98. Fuster V, Farkouh ME. Acute coronary syndromes and diabetes mellitus: a winning ticket for prasugrel. Circulation. 2008;118(16):1607-8.
99. 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(16):1626-36.
100. Angiolillo DJ, Bates ER, Bass TA. Clinical profile of prasugrel, a novel thienopyridine. Am Heart J. 2008;156(2 Suppl):S16-22.
101. 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 (PLATO) trial. Eur Heart J. 2010;31(24):3006-16.
102. Alber HF, Huber K, Pachinger O, et al. Prasugrel vs. ticagrelor in acute coronary syndromes: which one to choose? Wien Klin Wochenschr. 2011;123(15-16):468-76.
103. Alexopoulos D, Xanthopoulou I, Mavronasiou E, et al. Randomized assessment of ticagrelor versus prasugrel antiplatelet effects in patients with diabetes. Diabetes Care. 2013;36(8):2211-6.
104. Rydén L, Grant PJ, Anker SD, et al. ESC Guidelines on diabetes, pre-diabetes, and cardiovascular diseases developed in collaboration with the EASD: the Task Force on diabetes, pre-diabetes, and cardiovascular diseases of the European Society of Cardiology (ESC) and developed in collaboration with the European Association for the Study of Diabetes (EASD). Eur Heart J. Epub 2013 Aug 30.
105. Ferreiro JL, Ueno M, Tello-Montoliu A, et al. Effects of cangrelor in coronary artery disease patients with and without diabetes mellitus: an in vitro pharmacodynamic investigation. J Thromb Thrombolysis. 2013;35(2):155-64.
106. Wattanakit K, Cushman M, Stehman-Breen C, et al. Chronic kidney disease increases risk for venous thromboembolism. J Am Soc Nephrol. 2008;19(1):135-40.
107. Mezzano D, Tagle R, Panes O, et al. Hemostatic disorder of uremia: the platelet defect, main determinant of the prolonged bleeding time, is correlated with indices of activation of coagulation and fibrinolysis. Thromb Haemost. 1996;76(3):312-21. (Pubitemid 26373520)
108. Castillo R, Lozano T, Escolar G, et al. Defective platelet adhesion on vessel subendothelium in uremic patients. Blood. 1986;68(2):337-42. (Pubitemid 16050650)
109. Anavekar NS, McMurray JJ, Velazquez EJ, et al. Relation between renal dysfunction and cardiovascular outcomes after myocardial infarction. N Engl J Med. 2004;351(13):1285-95. (Pubitemid 39258422)
110. Best PJ, Lennon R, Ting HH, et al. The impact of renal insufficiency on clinical outcomes in patients undergoing percutaneous coronary interventions. J Am Coll Cardiol. 2002;39(7):1113-9. (Pubitemid 34267412)
111. Olesen JB, Lip GY, Kamper AL, et al. Stroke and bleeding in atrial fibrillation with chronic kidney disease. N Engl J Med. 2012;367(7):625-35.
112. Best PJ, Steinhubl SR, Berger PB, et al. The efficacy and safety of short- and long-term dual antiplatelet therapy in patients with mild or moderate chronic kidney disease: results from the Clopidogrel for the Reduction of Events During Observation (CREDO) trial. Am Heart J. 2008;155(4):687-93.
113. Keltai M, Tonelli M, Mann JF, et al. Renal function and outcomes in acute coronary syndrome: impact of clopidogrel. Eur J Cardiovasc Prev Rehabil. 2007;14(2):312-8. (Pubitemid 46650089)
114. Wrishko RE, Ernest CS 2nd, Small DS, et al. Population pharmacokinetic analyses to evaluate the influence of intrinsic and extrinsic factors on exposure of prasugrel active metabolite in TRITON-TIMI 38. J Clin Pharmacol. 2009;49(8):984-98.
115. 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(12):2379-85.
116. Butler K, Teng R. Pharmacokinetics, pharmacodynamics, and safety of ticagrelor in volunteers with severe renal impairment. J Clin Pharmacol. 2012;52(9):1388-98.
117. Alexopoulos D, Xanthopoulou I, Plakomyti TE, et al. Ticagrelor in clopidogrel-resistant patients undergoing maintenance hemodialysis. Am J Kidney Dis. 2012;60(2):332-3.
118. 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(11):1056-67.
119. Serebruany VL, Atar D. The PLATO trial: do you believe in magic? Eur Heart J. 2010;31(7):764-7.
120. Rajan L, Moliterno DJ. Beyond aspirin and clopidogrel: is there a need for additional antiplatelet therapy in ACS? Curr Cardiol Rep. 2011;13(4):303-11.
121. Burki NK, Dale WJ, Lee LY. Intravenous adenosine and dyspnea in humans. J Appl Physiol. 2005;98(1):180-5. (Pubitemid 40041245)
122. Wittfeldt A, Emanuelsson H, Brandrup-Wognsen G, et al. Ticagrelor enhances adenosine-induced coronary vasodilatory responses in humans. J Am Coll Cardiol. 2013;61(7):723-7.
123. Mehran R, Pocock SJ, Nikolsky E, et al. A risk score to predict bleeding in patients with acute coronary syndromes. J Am Coll Cardiol. 2010;55(23):2556-66.
124. Wittfeldt A, Emanuelsson H, Brandrup-Wognsen G, et al. Ticagrelor enhances adenosine-induced coronary vasodilatory responses in humans. J Am Coll Cardiol. 2013;61(7):723-7.
125. Cambou JP, Simon T, Mulak G, et al. The French registry of Acute ST elevation or non-ST-elevation Myocardial Infarction (FAST-MI): study design and baseline characteristics. Arch Mal Coeur Vaiss. 2007;100(6-7):524-34. (Pubitemid 47234424)
126. Kushner FG, Hand M, Smith SC Jr, et al. 2009 Focused Updates: ACC/AHA Guidelines for the Management of Patients With ST-Elevation Myocardial Infarction (updating the 2004 Guideline and 2007 Focused Update) and ACC/AHA/SCAI Guidelines on Percutaneous Coronary Intervention (updating the 2005 Guideline and 2007 Focused Update): a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation. 2009;120(22):2271-306.
127. Wiviott SD, Braunwald E, McCabe CH, et al. Prasugrel versus clopidogrel in patients with acute coronary syndromes. N Engl J Med. 2007;357(20):2001-15. (Pubitemid 350106708)
128. James SK, Storey RF, Khurmi NS, et al. Ticagrelor versus clopidogrel in patients with acute coronary syndromes and a history of stroke or transient ischemic attack. Circulation. 2012;125(23):2914-21.
129. 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):1821-30.
130. FDA. Safety alert. Plavix (clopidogrel): Reduced effectiveness in patients who are poor metabolizers of the drug. 2010. http://www.fda.gov/Safety/ MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm204256.htm. Last Accessed 5 Jan 2013.
131. 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):1409-11.
132. 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):512-8.
133. Grosdidier C, Quilici J, Loosveld M, et al. Effect of CYP2C19*2 and*17 genetic variants on platelet response to clopidogrel and prasugrel maintenance dose and relation to bleeding complications. Am J Cardiol. 2013;111(7):985-90.
134. Mega JL, Close SL, Wiviott SD, et al. Cytochrome p-450 polymorphisms and response to clopidogrel. N Engl J Med. 2009;360(4):354-62.
135. 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):849-57.
136. Varenhorst C, James S, Erlinge D, et al. Assessment of P2Y(12) inhibition with the point-of-care device VerifyNow P2Y12 in patients treated with prasugrel or clopidogrel coadministered with aspirin. Am Heart J. 2009;157(3):562.e1-9.
137. 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):2704-14.
138. Johnson JA, Roden DM, Lesko LJ, et al. Clopidogrel: a case for indication-specific pharmacogenetics. Clin Pharmacol Ther. 2012;91(5):774-6.
139. Hulot JS, Collet JP, Montalescot G. Thienopyridine-associated drug-drug interactions: pharmacologic mechanisms and clinical relevance. Curr Cardiol Rep. 2011;13(5):451-8.
140. Jeong YH, Hwang JY, Kim IS, et al. Adding cilostazol to dual antiplatelet therapy achieves greater platelet inhibition than high maintenance dose clopidogrel in patients with acute myocardial infarction: Results of the adjunctive cilostazol versus high maintenance dose clopidogrel in patients with AMI (ACCEL-AMI) study. Circ Cardiovasc Interv. 2010;3(1):17-26.
141. Kim JY. Strategy for the treatment of clopidogrel low responsiveness in diabetes mellitus and stent implantation. Korean Circ J. 2009;39(11):459-61.
142. Bhindi R, Ormerod O, Newton J, et al. Interaction between statins and clopidogrel: is there anything clinically relevant? QJM. 2008;101(12):915-25.
143. Rolan PE. Plasma protein binding displacement interactions-why are they still regarded as clinically important? Br J Clin Pharmacol. 1994;37(2):125-8. (Pubitemid 24213753)
144. Ganesan S, Williams C, Maslen CL, et al. Clopidogrel variability: role of plasma protein binding alterations. Br J Clin Pharmacol. 2013;75(6):1468-77.
145. Weber AA, Reimann S, Schror K. Specific inhibition of ADP-induced platelet aggregation by clopidogrel in vitro. Br J Pharmacol. 1999;126(2):415-20. (Pubitemid 29057591)
146. Silvain J, Cayla G, Hulot JS, et al. High on-thienopyridine platelet reactivity in elderly coronary patients: the SENIOR-PLATELET study. Eur Heart J. 2012;33(10):1241-9.
147. Feit F, Voeltz MD, Attubato MJ, et al. Predictors and impact of major hemorrhage on mortality following percutaneous coronary intervention from the REPLACE-2 Trial. Am J Cardiol. 2007;100(9):1364-9. (Pubitemid 47576015)
148. MedicineComplete. Stockley's interaction alerts. 2013. http://www.medicinescomplete.com/mc/alerts/current/interactions.htm?q= clopidogrel&searchButton=Search. Last Accessed 6 Jan 2013.
149. Gibaldi M. Pharmacokinetic variability-drug interactions. 4th ed. Philadelphia: Lea & Febiger; 1991. p. 305-43.
150. 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):321-41.
151. Angiolillo DJ, Gibson CM, Cheng S, et al. Differential effects of omeprazole and pantoprazole on the pharmacodynamics and pharmacokinetics of clopidogrel in healthy subjects: randomized, placebo-controlled, crossover comparison studies. Clin Pharmacol Ther. 2011;89(1):65-74.
152. FDA. Safety alert. Clopidogrel (marketed as Plavix) and Omeprazole (marketed as Prilosec) - Drug Interaction. 2009. http://www.fda.gov/Safety/ MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm190848.htm. Last Accessed 5 Jan 2013.
153. Bhatt DL, Cryer BL, Contant CF, et al. Clopidogrel with or without omeprazole in coronary artery disease. N Engl J Med. 2010;363(20):1909-17.
154. Burkard T, Kaiser CA, Brunner-La Rocca H, et al. Combined clopidogrel and proton pump inhibitor therapy is associated with higher cardiovascular event rates after percutaneous coronary intervention: a report from the BASKET trial. J Intern Med. 2012;271(3):257-63.
155. Abraham NS, Hlatky MA, Antman EM, et al. 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(24):2051-66.
156. O'Donoghue M, Antman EM, Braunwald E, et al. The efficacy and safety of prasugrel with and without a glycoprotein IIb/IIIa inhibitor in patients with acute coronary syndromes undergoing percutaneous intervention: a TRITON-TIMI 38 (Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition With Prasugrel-Thrombolysis In Myocardial Infarction 38) analysis. J Am Coll Cardiol. 2009;54(8):678-85.
157. Hulot JS, Collet JP, Silvain J, 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(2):134-43.
158. Bellosta S, Corsini A. Statin drug interactions and related adverse reactions. Expert Opin Drug Saf. 2012;11(6):933-46.
159. Farid NA, Payne CD, Small DS, et al. Cytochrome P450 3A inhibition by ketoconazole affects prasugrel and clopidogrel pharmacokinetics and pharmacodynamics differently. Clin Pharmacol Ther. 2007;81(5):735-41. (Pubitemid 46625113)
160. Siller-Matula JM, Lang I, Christ G, et al. Calcium-channel blockers reduce the antiplatelet effect of clopidogrel. J Am Coll Cardiol. 2008;52(19):1557-63.
161. Jeong YH, Cho JH, Kang MK, et al. Smoking at least 10 cigarettes per day increases platelet inhibition by clopidogrel in patients with ST-segment-elevation myocardial infarction. Thromb Res. 2010;126(4):e334-8.
162. Lev EI, Arikan ME, Vaduganathan M, et al. Effect of caffeine on platelet inhibition by clopidogrel in healthy subjects and patients with coronary artery disease. Am Heart J. 2007;154(4):694.e1-7.
163. Small DS, Farid NA, Payne CD, et al. Effects of the proton pump inhibitor lansoprazole on the pharmacokinetics and pharmacodynamics of prasugrel and clopidogrel. J Clin Pharmacol. 2008;48(4):475-84. (Pubitemid 351389118)
164. O'Donoghue ML, Braunwald E, Antman EM, et al. 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(9694):989-97.
165. Schror K, Siller-Matula JM, Huber K. Pharmacokinetic basis of the antiplatelet action of prasugrel. Fundam Clin Pharmacol. 2012;26(1):39-46.
166. Dinicolantonio JJ, Serebruany VL. Exploring the ticagrelor-statin interplay in the PLATO trial. Cardiology. 2013;124(2):105-7.
167. Schneider DJ, Tracy PB, Mann KG, et al. Differential effects of anticoagulants on the activation of platelets ex vivo. Circulation. 1997;96(9):2877-83. (Pubitemid 27500085)
168. 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(6):672-84.
169. Biondi-Zoccai G, Lotrionte M, Agostoni P, et al. Adjusted indirect comparison meta-analysis of prasugrel versus ticagrelor for patients with acute coronary syndromes. Int J Cardiol. 2011;150(3):325-31.
170. Bhatt DL, Lincoff AM, Gibson CM, et al. Intravenous platelet blockade with cangrelor during PCI. N Engl J Med. 2009;361(24):2330-41.
171. Harrington RA, Stone GW, McNulty S, et al. Platelet inhibition with cangrelor in patients undergoing PCI. N Engl J Med. 2009;361(24):2318-29.
172. Leonardi S, Mahaffey KW, White HD, et al. Rationale and design of the Cangrelor versus standard therapy to acHieve optimal Management of Platelet InhibitiON PHOENIX trial. Am Heart J. 2012;163(5):768-76.e2.
173. Bhatt DL, Stone GW, Mahaffey KW, et al. Effect of platelet inhibition with cangrelor during PCI on ischemic events. N Engl J Med. 2013;368(14):1303- 13.
174. Di Virgilio F, Solini A. P2 receptors: new potential players in atherosclerosis. Br J Pharmacol. 2002;135(4):831-42. (Pubitemid 34214442)
175. Massberg S, Brand K, Gruner S, et al. A critical role of platelet adhesion in the initiation of atherosclerotic lesion formation. J Exp Med. 2002;196(7):887-96.
176. Massberg S, Schurzinger K, Lorenz M, et al. Platelet adhesion via glycoprotein IIb integrin is critical for atheroprogression and focal cerebral ischemia: an in vivo study in mice lacking glycoprotein IIb. Circulation. 2005;112(8):1180-8. (Pubitemid 41216125)
177. Frelinger AL 3rd, Jakubowski JA, Li Y, et al. The active metabolite of prasugrel inhibits ADP-stimulated thrombo-inflammatory markers of platelet activation: Influence of other blood cells, calcium, and aspirin. Thromb Haemost. 2007;98(1):192-200. (Pubitemid 47074196)
178. Klinkhardt U, Bauersachs R, Adams J, et al. Clopidogrel but not aspirin reduces P-selectin expression and formation of platelet-leukocyte aggregates in patients with atherosclerotic vascular disease. Clin Pharmacol Ther. 2003;73(3):232-41. (Pubitemid 36269674)
179. Hagiwara S, Iwasaka H, Hasegawa A, et al. Adenosine diphosphate receptor antagonist clopidogrel sulfate attenuates LPS-induced systemic inflammation in a rat model. Shock. 2011;35(3):289-92.
180. Liu Y, Gao XM, Fang L, et al. Novel role of platelets in mediating inflammatory responses and ventricular rupture or remodeling following myocardial infarction. Arterioscler Thromb Vasc Biol. 2011;31(4):834-41.
181. Totani L, Dell'Elba G, Martelli N, et al. Prasugrel inhibits platelet-leukocyte interaction and reduces inflammatory markers in a model of endotoxic shock in the mouse. Thromb Haemost. 2012;107(6):1130-40.
182. Evangelista V, Manarini S, Dell'Elba G, et al. Clopidogrel inhibits platelet-leukocyte adhesion and platelet-dependent leukocyte activation. Thromb Haemost. 2005;94(3):568-77. (Pubitemid 41300854)
183. Winning J, Reichel J, Eisenhut Y, et al. Anti-platelet drugs and outcome in severe infection: clinical impact and underlying mechanisms. Platelets. 2009;20(1):50-7.
184. Lee CW, Hwang I, Park CS, et al. Comparison of differential expression of P2Y(1)(2) receptor in culprit coronary plaques in patients with acute myocardial infarction versus stable angina pectoris. Am J Cardiol. 2011;108(6):799-803.
185. Rauch BH, Rosenkranz AC, Ermler S, et al. Regulation of functionally active P2Y12 ADP receptors by thrombin in human smooth muscle cells and the presence of P2Y12 in carotid artery lesions. Arterioscler Thromb Vasc Biol. 2010;30(12):2434-42.
186. Harada K, Matsumoto Y, Umemura K. Adenosine diphosphate receptor P2Y12-mediated migration of host smooth muscle-like cells and leukocytes in the development of transplant arteriosclerosis. Transplantation. 2011;92(2):148-54.
187. Zeiffer U, Schober A, Lietz M, et al. Neointimal smooth muscle cells display a proinflammatory phenotype resulting in increased leukocyte recruitment mediated by P-selectin and chemokines. Circ Res. 2004;94(6):776-84. (Pubitemid 38451739)
188. Chew DP, Bhatt DL, Robbins MA, et al. Effect of clopidogrel added to aspirin before percutaneous coronary intervention on the risk associated with C-reactive protein. Am J Cardiol. 2001;88(6):672-4. (Pubitemid 32831103)
189. Xiao Z, Theroux P. Clopidogrel inhibits platelet-leukocyte interactions and thrombin receptor agonist peptide-induced platelet activation in patients with an acute coronary syndrome. J Am Coll Cardiol. 2004;43(11):1982-8. (Pubitemid 38686790)
190. Cha JK, Jeong MH, Lee KM, et al. Changes in platelet P-selectin and in plasma C-reactive protein in acute atherosclerotic ischemic stroke treated with a loading dose of clopidogrel. J Thromb Thrombolysis. 2002;14(2):145-50.
191. Hermann A, Rauch BH, Braun M, et al. Platelet CD40 ligand (CD40L) - subcellular localization, regulation of expression, and inhibition by clopidogrel. Platelets. 2001;12(2):74-82. (Pubitemid 32281113)
192. Husted S, Storey RF, Harrington RA, et al. Changes in inflammatory biomarkers in patients treated with ticagrelor or clopidogrel. Clin Cardiol. 2010;33(4):206-12.
193. Afek A, Kogan E, Maysel-Auslender S, et al. Clopidogrel attenuates atheroma formation and induces a stable plaque phenotype in apolipoprotein E knockout mice. Microvasc Res. 2009;77(3):364-9.
194. Schulz C, Konrad I, Sauer S, et al. Effect of chronic treatment with acetylsalicylic acid and clopidogrel on atheroprogression and atherothrombosis in ApoE-deficient mice in vivo. Thromb Haemost. 2008;99(1):190-5.
195. Li M, Zhang Y, Ren H, et al. Effect of clopidogrel on the inflammatory progression of early atherosclerosis in rabbits model. Atherosclerosis. 2007;194(2):348-56. (Pubitemid 47513098)
196. Li D, Wang Y, Zhang L, et al. Roles of purinergic receptor P2Y, G protein-coupled 12 in the development of atherosclerosis in apolipoprotein E-deficient mice. Arterioscler Thromb Vasc Biol. 2012;32(8):e81-9.
197. Sachais BS, Turrentine T, Dawicki McKenna JM, et al. Elimination of platelet factor 4 (PF4) from platelets reduces atherosclerosis in C57Bl/6 and apoE-/- mice. Thromb Haemost. 2007;98(5):1108-13. (Pubitemid 350091140)
198. Sugidachi A, Yamaguchi S, Jakubowski JA, et al. Selective blockade of P2Y12 receptors by prasugrel inhibits myocardial infarction induced by thrombotic coronary artery occlusion in rats. J Cardiovasc Pharmacol. 2011;58(3):329-34.
199. Siller-Matula JM, Krumphuber J, Jilma B. Pharmacokinetic, pharmacodynamic and clinical profile of novel antiplatelet drugs targeting vascular diseases. Br J Pharmacol. 2010;159(3):502-17.
200. Roe MT, Armstrong PW, Fox KA, et al. Prasugrel versus clopidogrel for acute coronary syndromes without revascularization. N Engl J Med. 2012;367(14):1297-309.
201. Wouter Jukema J, Collet JP, De Luca L. Antiplatelet therapy in patients with ST-elevation myocardial infarction undergoing myocardial revascularisation: beyond clopidogrel. Curr Med Res Opin. 2012;28(2):203-11.