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Medicina & Laboratorio

2017, Number 01-02

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Medicina & Laboratorio 2017; 23 (01-02)

Platelet P2Y12 receptor inhibitors. Part 1 of 2: Scenario of action, pharmacology, clinical application, and limitations of its use

Campuzano-Maya G

Language: Spanish
References: 168
Page: 13-44
PDF size: 1712.62 Kb.


ABSTRACT

Cardiovascular diseases, including in general heart diseases, brain, and blood vessels are the leading cause of death worldwide with 17.000.000 of deaths each year. Primary and secondary prevention of atherothrombotic diseases, as acute myocardial infarction, stroke, and thrombotic disorders, besides to the general measures for risk factors control such as obesity, sedentary lifestyle, smoke, high blood pressure, and diabetes, have focused on platelet aggregation control. The antiplatelet agent par excellence or universal, especially in primary prevention, is aspirin, and dual therapy with the combination of aspirin and a platelet receptor inhibitor P2Y12, with clopidogrel as the most used, for secondary prevention and in cases of aspirin resistance. Currently, six P2Y12 platelet receptor inhibitors are available for clinical use: ticlopidine, clopidogrel, prasugrel, ticagrelor, cangrelor, and elinogrel. In this first of two modules, the use of P2Y12 receptor inhibitors in daily practice in the primary and secondary prevention of atherothrombotic diseases will be addressed focused on the analysis of the platelets role in atherothrombotic disease pathophysiology and description of the six P2Y12 platelet receptor inhibitors available now and in the future. In a second module, we will approach the concept of resistance to platelet P2Y12 receptor inhibitors, its diagnosis from the laboratory point of view and the different management alternatives when resistance to one of these drugs is present.


REFERENCES

  1. Word Health Organitation, World Heart Federation, World Stroke Organization. Global atlas on cardiovascular disease prevention and control. Policies, strategies and interventions. Ginebra, Suiza: 2011.

  2. Yusuf S, Reddy S, Ounpuu S, Anand S. Global burden of cardiovascular diseases: part I: general considerations, the epidemiologic transition, risk factors, and impact of urbanization. Circulation 2001;104:2746-2753.

  3. Yusuf S, Reddy S, Ounpuu S, Anand S. Global burden of cardiovascular diseases: Part II: variations in cardiovascular disease by specific ethnic groups and geographic regions and prevention strategies. Circulation 2001;104:2855- 2864.

  4. World Health Organization. Disease and injury country estimates: Burden of Disease. Ginebra, Suiza: WHO, 2008.

  5. García G, Ronald G, López-Jaramillo P. Uso de aspirina en la prevención de enfermedades cardiovasculares. Rev Colomb Cardiol 2008;15:223-230.

  6. López-Jaramillo P, Casas JP, Bautista L, Serrano NC, Morillo CA. An integrated proposal to explain the epidemic of cardiovascular disease in a developing country. From socioeconomic factors to free radicals. Cardiology 2001;96:1-6.

  7. Machado-Alba J, García S, Calvo-Torres LF, Bañol-Giraldo AM. Patrones de prescripción del ácido salicílico. Rev Colomb Cardiol 2015;22:127-135.

  8. Weisman SM, Graham DY. Evaluation of the benefits and risks of low-dose aspirin in the secondary prevention of cardiovascular and cerebrovascular events. Arch Intern Med 2002;162:2197-2202.

  9. Srinath Reddy K, Katan MB. Diet, nutrition and the prevention of hypertension and cardiovascular diseases. Public Health Nutr 2004;7:167-186.

  10. Thompson PD, Buchner D, Pina IL, Balady GJ, Williams MA, Marcus BH, et al. Exercise and physical activity in the prevention and treatment of atherosclerotic cardiovascular disease: a statement from the Council on Clinical Cardiology (Subcommittee on Exercise, Rehabilitation, and Prevention) and the Council on Nutrition, Physical Activity, and Metabolism (Subcommittee on Physical Activity). Circulation 2003;107:3109-3116.

  11. Rigotti NA, Pasternak RC. Cigarette smoking and coronary heart disease: risks and management. Cardiol Clin 1996;14:51-68.

  12. Stratton IM, Adler AI, Neil HA, Matthews DR, Manley SE, Cull CA, et al. Association of glycaemia with macrovascular and microvascular complications of type 2 diabetes (UKPDS 35): prospective observational study. BMJ 2000;321:405-412.

  13. Chobanian AV, Bakris GL, Black HR, Cushman WC, Green LA, Izzo JL, Jr., et al. Seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. Hypertension 2003;42:1206-1252.

  14. Miner SE, Nield LE. Obesity cardiovascular disease and the failure of public health education. J Am Coll Cardiol 2016;67:2315-2316.

  15. National Cholesterol Education Program Expert Panel on Detection E, Treatment of High Blood Cholesterol in A. Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) final report. Circulation 2002;106:3143- 3421.

  16. World Health Organization. 19th WHO Model List of Essential Medicines. Ginebra, Suiza: 2015.

  17. Antithrombotic Trialists Collaboration. Collaborative meta-analysis of randomised trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high risk patients. BMJ 2002;324:71-86.

  18. Becker RC, Meade TW, Berger PB, Ezekowitz M, O’Connor CM, Vorchheimer DA, et al. The primary and secondary prevention of coronary artery disease: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest 2008;133:776S-814S.

  19. Gurbel PA, Tantry US. Combination antithrombotic therapies. Circulation 2010;121:569-583.

  20. Klonaris C, Patelis N, Drebes A, Matheiken S, Liakakos T. Antiplatelet treatment in peripheral arterial disease: The role of novel antiplatelet agents. Curr Pharm Des 2016.

  21. Hirsh J, Fuster V, Ansell J, Halperin JL, American Heart A, American College of Cardiology F. American Heart Association/ American College of Cardiology Foundation guide to warfarin therapy. Circulation 2003;107:1692-1711.

  22. Tantry US, Etherington A, Bliden KP, Gurbel PA. Antiplatelet therapy: current strategies and future trends. Future Cardiol 2006;2:343-366.

  23. Gurbel PA, Antonino MJ, Tantry US. Antiplatelet treatment of cardiovascular disease: a translational research perspective. Pol Arch Med Wewn 2008;118:289-297.

  24. Gurbel PA, Tantry US. Selecting optimal antiplatelet therapy based on platelet function monitoring in patients with coronary artery disease. Curr Treat Options Cardiovasc Med 2009;11:22-32.

  25. Hulot JS, Fuster V. Antiplatelet therapy: Personalized medicine for clopidogrel resistance? Nat Rev Cardiol 2009;6:334-336.

  26. Geisler T, Gawaz M, Steinhubl SR, Bhatt DL, Storey RF, Flather M. Current strategies in antiplatelet therapy--does identification of risk and adjustment of therapy contribute to more effective, personalized medicine in cardiovascular disease? Pharmacol Ther 2010;127:95-107.

  27. Collet JP, Cayla G, Cuisset T, Elhadad S, Range G, Vicaut E, et al. Randomized comparison of platelet function monitoring to adjust antiplatelet therapy versus standard of care: rationale and design of the assessment with a double randomization of (1) a fixed dose versus a monitoring-guided dose of aspirin and clopidogrel after DES implantation, and (2) treatment interruption versus continuation, 1 year after stenting (ARCTIC) study. Am Heart J 2011;161:5-12 e15.

  28. de Labriolle A, Doazan JP, Lemesle G, Bonello L. Genotypic and phenotypic assessment of platelet function and response to P2Y12 antagonists. Curr Cardiol Rep 2011;13:439-450.

  29. Lassar TA, Simon DI, Croce K. Optimizing antiplatelet therapy following percutaneous coronary intervention: clinical pathways for platelet function testing. Rev Cardiovasc Med 2011;12 Suppl 1:S23-33.

  30. Müller KA, Geisler T, Gawaz M. Elinogrel, an orally and intravenously available ADP-receptor antagonist. How does elinogrel affect a personalized antiplatelet therapy? Hamostaseologie 2012;32:191-194.

  31. Sambu N, Radhakrishnan A, Dent H, Calver AL, Corbett S, Gray H, et al. Personalised antiplatelet therapy in stent thrombosis: observations from the Clopidogrel Resistance in Stent Thrombosis (CREST) registry. Heart 2012;98:706-711.

  32. Uhry S, Bessereau J, Camoin-Jau L, Paganelli F, Bonello L. Latest evidence in personalized antiplatelet therapy in patients with acute coronary syndromes undergoing percutaneous coronary intervention. Hosp Pract (1995) 2012;40:104-117.

  33. Tantry US, Bonello L, Aradi D, Price MJ, Jeong YH, Angiolillo DJ, et al. Consensus and update on the definition of on-treatment platelet reactivity to adenosine diphosphate associated with ischemia and bleeding. J Am Coll Cardiol 2013;62:2261-2273.

  34. Lenk E, Spannagl M. Platelet function testing-guided antiplatelet therapy. EJIFCC 2013;24:90-96.

  35. Xie X, Ma YT, Yang YN, Li XM, Zheng YY, Ma X, et al. Personalized antiplatelet therapy according to CYP2C19 genotype after percutaneous coronary intervention: a randomized control trial. Int J Cardiol 2013;168:3736-3740.

  36. Straub N, Beivers A, Lenk E, Aradi D, Sibbing D. A model- based analysis of the clinical and economic impact of personalising P2Y12-receptor inhibition with platelet function testing in acute coronary syndrome patients. Thromb Haemost 2014;111:290-299.

  37. Malhotra N, Abunassar J, Wells GA, McPherson R, Fu A, Hibbert B, et al. A pharmacodynamic comparison of a personalized strategy for anti-platelet therapy versus ticagrelor in achieving a therapeutic window. Int J Cardiol 2015;197:318-325.

  38. Stimpfle F, Geisler T. Impact of tailored anti-P2Y12 therapies in acute coronary syndromes. Pharmacogenomics 2015;16:493-499.

  39. Naimo PS, McGiffin D, Konstantinov IE. Aspirin resistance in the era of personalized medicine: Should we not take it personally? J Thorac Cardiovasc Surg 2015;150:e99- e100.

  40. Winter MP, Kozinski M, Kubica J, Aradi D, Siller-Matula JM. Personalized antiplatelet therapy with P2Y12 receptor inhibitors: benefits and pitfalls. Postepy Kardiol Interwencyjnej 2015;11:259-280.

  41. Sridharan K, Kataria R, Tolani D, Bendkhale S, Gogtay NJ, Thatte UM. Evaluation of CYP2C19, P2Y12, and ABCB1 polymorphisms and phenotypic response to clopidogrel in healthy Indian adults. Indian J Pharmacol 2016;48:350-354.

  42. Campuzano-Maya G. Editorial. Resistencia a la aspirina: llegó el momento de detectarla y de personalizar cada trtatamiento. . Medicina & Laboratorio 2016;22:9-12.

  43. Barilla F, Pelliccia F, Borzi M, Camici P, Cas LD, Di Biase M, et al. Optimal duration of dual anti-platelet therapy after percutaneous coronary intervention: 2016 consensus position of the Italian Society of Cardiology. J Cardiovasc Med (Hagerstown) 2017;18:1-9.

  44. Hamm CW, Bassand JP, Agewall S, Bax J, Boersma E, Bueno H, et al. ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation: The Task Force for the management of acute coronary syndromes (ACS) in patients presenting without persistent ST-segment elevation of the European Society of Cardiology (ESC). Eur Heart J 2011;32:2999-3054.

  45. Jneid H, Anderson JL, Wright RS, Adams CD, Bridges CR, Casey DE, Jr., et al. 2012 ACCF/AHA focused update of the guideline for the management of patients with unstable angina/ non-ST-elevation myocardial infarction (updating the 2007 guideline and replacing the 2011 focused update): a report of the American College of Cardiology Foundation/ American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol 2012;60:645-681.

  46. Levine GN, Bates ER, Blankenship JC, Bailey SR, Bittl JA, Cercek B, et al. 2011 ACCF/AHA/SCAI guideline for percutaneous coronary intervention: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines and the Society for Cardiovascular Angiography and Interventions. Catheter Cardiovasc Interv 2013;82:E266-355.

  47. Levine GN, Bates ER, Blankenship JC, Bailey SR, Bittl JA, Cercek B, et al. 2015 ACC/AHA/SCAI focused update on primary percutaneous coronary intervention for patients with ST-elevation myocardial infarction: An update of the 2011 ACCF/AHA/SCAI guideline for percutaneous coronary intervention and the 2013 ACCF/AHA guideline for the management of ST-elevation myocardial infarction: A report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Society for Cardiovascular Angiography and Interventions. Circulation 2016;133:1135-1147.

  48. Levine GN, Bates ER, Bittl JA, Brindis RG, Fihn SD, Fleisher LA, et al. 2016 ACC/AHA guideline focused update on duration of dual antiplatelet therapy in patients with coronary artery disease: A Report of the American College of Cardiology/ American Heart Association Task Force on Clinical Practice Guidelines: An update of the 2011 ACCF/AHA/SCAI guideline for percutaneous coronary intervention, 2011 ACCF/AHA guideline for coronary artery bypass graft surgery, 2012 ACC/AHA/ACP/AATS/PCNA/SCAI/STS guideline for the diagnosis and management of patients with stable ischemic heart disease, 2013 ACCF/AHA guideline for the management of ST-elevation myocardial infarction, 2014 AHA/ACC guideline for the management of patients with non-ST-elevation acute coronary syndromes, and 2014 ACC/ AHA guideline on perioperative cardiovascular evaluation and management of patients undergoing noncardiac surgery. Circulation 2016;134:e123-155.

  49. Gurbel PA, Tantry US. Monitoring of antiplatelet therapy. In: Platelets, edited by Michelson AD. Philadelphia, USA: Academic Press, 2013, p. 603-634.

  50. Campuzano-Maya G. Resistencia a la aspirina: un problema letante de alto riesgo. . Medicina & Laboratorio 2016;22:411-448.

  51. Harrison P, Briggs C. Platelet counting. In: Platelets, edited by Michelson AD. Philadelphia, USA: Academic Press, 2013, p. 547-557.

  52. Leeksma CH, Cohen JA. Determination of the life span of human blood platelets using labelled diisopropylfluorophosphonate. J Clin Invest 1956;35:964-969.

  53. Josefsson EC, Dowling MR, Lebois M, Kile BT. The regulation of platelet life span. In: Platelets, edited by Michelson AD. Philadelphia, USA: Academic Press, 2013, p. 51-66.

  54. Campuzano-Maya G. Del hemograma manual al hemograma de cuarta generación. Medicina & Laboratorio 2007;13:551-550.

  55. Cesari F, Marcucci R, Caporale R, Paniccia R, Romano E, Gensini GF, et al. Relationship between high platelet turnover and platelet function in high-risk patients with coronary artery disease on dual antiplatelet therapy. Thromb Haemost 2008;99:930-935.

  56. Guthikonda S, Alviar CL, Vaduganathan M, Arikan M, Tellez A, DeLao T, et al. Role of reticulated platelets and platelet size heterogeneity on platelet activity after dual antiplatelet therapy with aspirin and clopidogrel in patients with stable coronary artery disease. J Am Coll Cardiol 2008;52:743-749.

  57. Sociedad Colombiana de Patología Clínica. Manual de Codificación, Nomenclatura, Nivelación y Valores de Exámenes de laboratorio Clínico. Medellín, Colombia: Edimeco S.A., 2016, p. 1-100.

  58. Ali SA, Shaikh MS. Clinical utility of immature platelet fraction. An advanced parameter in laboratory hematology. J Coll Physicians Surg Pak 2016;26:798-799.

  59. Badimon L, Padro T, Vilahur G. Atherosclerosis, platelets and thrombosis in acute ischaemic heart disease. Eur Heart J Acute Cardiovasc Care 2012;1:60-74.

  60. Badimon L, Vilahur G. Coronary atherothrombotic disease: progress in antiplatelet therapy. Rev Esp Cardiol 2008;61:501-513.

  61. Michelson AD. Antiplatelet therapies for the treatment of cardiovascular disease. Nat Rev Drug Discov 2010;9:154-169.

  62. Franchi F, Angiolillo DJ. Novel antiplatelet agents in acute coronary syndrome. Nat Rev Cardiol 2015;12:30-47.

  63. Angiolillo DJ, Fernandez-Ortiz A, Bernardo E, Alfonso F, Macaya C, Bass TA, et al. Variability in individual responsiveness to clopidogrel: clinical implications, management, and future perspectives. J Am Coll Cardiol 2007;49:1505-1516.

  64. Angiolillo DJ, Ferreiro JL. Platelet adenosine diphosphate P2Y12 receptor antagonism: benefits and limitations of current treatment strategies and future directions. Rev Esp Cardiol 2010;63:60-76.

  65. Gachet C. P2 receptors, platelet function and pharmacological implications. Thromb Haemost 2008;99:466-472.

  66. Roth GJ, Calverley DC. Aspirin, platelets, and thrombosis: theory and practice. Blood 1994;83:885-898.

  67. McNicol A, Israels SJ. Platelets and anti-platelet therapy. J Pharmacol Sci 2003;93:381-396.

  68. Patrono C, Coller B, FitzGerald GA, Hirsh J, Roth G. Platelet-active drugs: the relationships among dose, effectiveness, and side effects: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest 2004;126:234S-264S.

  69. Franchi F, Rollini F, Park Y, Angiolillo DJ. Novel antiplatelet agents: The current state and what is coming down the pike. Prog Cardiovasc Dis 2015;58:267-277.

  70. De Marco L, Mazzucato M, Masotti A, Ruggeri ZM. Localization and characterization of an alpha-thrombin-binding site on platelet glycoprotein Ib alpha. J Biol Chem 1994;269:6478-6484.

  71. De Candia E, Hall SW, Rutella S, Landolfi R, Andrews RK, De Cristofaro R. Binding of thrombin to glycoprotein Ib accelerates the hydrolysis of Par-1 on intact platelets. J Biol Chem 2001;276:4692-4698.

  72. Jackson SP, Schoenwaelder SM. Antiplatelet therapy: in search of the ‘magic bullet’. Nat Rev Drug Discov 2003;2:775-789.

  73. 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.

  74. Alexopoulos D. P2Y12 inhibitors adjunctive to primary PCI therapy in STEMI: fighting against the activated platelets. Int J Cardiol 2013;163:249-255.

  75. Giossi A, Pezzini A, Del Zotto E, Volonghi I, Costa P, Ferrari D, et al. Advances in antiplatelet therapy for stroke prevention: the new P2Y12 antagonists. Curr Drug Targets 2010;11:380-391.

  76. Maffrand JP, Eloy F. Synthesis of thioenopyridines and furopyridines of therapeutic interest. Eur J Med Chem 1974;9:483-486.

  77. U.S. Food & Drug Administration, Center for Drug Evaluation and Research. Approval Package for: Aplication number 19-979/S-018, Final Printed Labeling: Ticlid®(ticlopidine hydrochloride) tablets. Maryland, Estados Unidos: 2001.

  78. Schomig A, Neumann FJ, Kastrati A, Schuhlen H, Blasini R, Hadamitzky M, 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.

  79. Yoneda K, Iwamura R, Kishi H, Mizukami Y, Mogami K, Kobayashi S. Identification of the active metabolite of ticlopidine from rat in vitro metabolites. Br J Pharmacol 2004;142:551-557.

  80. Kam PC, Nethery CM. The thienopyridine derivatives (platelet adenosine diphosphate receptor antagonists), pharmacology and clinical developments. Anaesthesia 2003;58:28-35.

  81. Kuzniar J, Splawinska B, Malinga K, Mazurek AP, Splawinski J. Pharmacodynamics of ticlopidine: relation between dose and time of administration to platelet inhibition. Int J Clin Pharmacol Ther 1996;34:357-361.

  82. Belanger P, Palisaitis DA, Diodati JG, Pharand C. Effects of high ticlopidine doses on platelet function in acute coronary syndrome patients. J Cardiovasc Pharmacol 2004;43:128-132.

  83. Carlson JA, Maesner JE. Fatal neutropenia and thrombocytopenia associated with ticlopidine. Ann Pharmacother 1994;28:1236-1238.

  84. 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.

  85. Bennett CL, Davidson CJ, Raisch DW, Weinberg PD, Bennett RH, Feldman MD. Thrombotic thrombocytopenic purpura associated with ticlopidine in the setting of coronary artery stents and stroke prevention. Arch Intern Med 1999;159:2524-2528.

  86. Farver DK, Hansen LA. Delayed neutropenia with ticlopidine. Ann Pharmacother 1994;28:1344-1346.

  87. Haushofer A, Halbmayer WM, Prachar H. Neutropenia with ticlopidine plus aspirin. Lancet 1997;349:474-475.

  88. Yeh SP, Hsueh EJ, Wu H, Wang YC. Ticlopidine-associated aplastic anemia. A case report and review of literature. Ann Hematol 1998;76:87-90.

  89. U.S. Food & Drug Administration, Center for Drug Evaluation and Research. Approval Package for Aplication number 20-839/SE1-019, Final Printed Labeling: Plavix® clopidogrel bisulfate tablets. Maryland, Estados Unidos: 2002.

  90. Zhang Y, Zhang S, Ding Z. Role of P2Y12 receptor in thrombosis. Adv Exp Med Biol 2017;906:307-324.

  91. Siller-Matula JM, Trenk D, Krahenbuhl S, Michelson AD, Delle-Karth G. Clinical implications of drug-drug interactions with P2Y12 receptor inhibitors. J Thromb Haemost 2014;12:2-13.

  92. Patti G, Pasceri V, Mangiacapra F, Colonna G, Vizzi V, Ricottini E, et al. Efficacy of clopidogrel reloading in patients with acute coronary syndrome undergoing percutaneous coronary intervention during chronic clopidogrel therapy (from the Antiplatelet therapy for Reduction of MYocardial Damage during Angioplasty [ARMYDA-8 RELOAD- ACS] trial). Am J Cardiol 2013;112:162-168.

  93. O’Gara PT, Kushner FG, Ascheim DD, Casey DE, Jr., Chung MK, de Lemos JA, et al. 2013 ACCF/AHA guideline for the management of ST-elevation myocardial infarction: a report of the American College of Cardiology Foundation/ American Heart Association Task Force on Practice Guidelines. Circulation 2013;127:e362-425.

  94. Bhatt DL, Bertrand ME, Berger PB, L’Allier PL, Moussa I, Moses JW, et al. Meta-analysis of randomized and registry comparisons of ticlopidine with clopidogrel after stenting. J Am Coll Cardiol 2002;39:9-14.

  95. Shah R, Keough LA, Belalcazar-Portacio A, Ramanathan KB. Ticagrelor as an alternative in clopidogrel-associated neutropenia. Platelets 2015;26:80-82.

  96. Lokhandwala JO, Best PJ, Butterfield JH, Skelding KA, Scott T, Blankenship JC, et al. Frequency of allergic or hematologic adverse reactions to ticlopidine among patients with allergic or hematologic adverse reactions to clopidogrel. Circ Cardiovasc Interv 2009;2:348-351.

  97. Wallentin L, Becker RC, Budaj A, Cannon CP, Emanuelsson H, Held C, et al. Ticagrelor versus clopidogrel in patients with acute coronary syndromes. N Engl J Med 2009;361:1045-1057.

  98. Jarvis B, Simpson K. Clopidogrel: a review of its use in the prevention of atherothrombosis. Drugs 2000;60:347- 377.

  99. Angiolillo DJ, Capranzano P. Pharmacology of emerging novel platelet inhibitors. Am Heart J 2008;156:S10-15.

  100. U.S. Food & Drug Administration. Highlights of prescribing information: Effient (prasugrel) tablets. Maryland, Estados Unidos: 2010.

  101. Coons JC, Schwier N, Harris J, Seybert AL. Pharmacokinetic evaluation of prasugrel for the treatment of myocardial infarction. Expert Opin Drug Metab Toxicol 2014;10:609-620.

  102. Wiviott SD, Braunwald E, McCabe CH, Montalescot G, Ruzyllo W, Gottlieb S, et al. Prasugrel versus clopidogrel in patients with acute coronary syndromes. N Engl J Med 2007;357:2001-2015.

  103. Almendro-Delia M, Blanco Ponce E, Gomez- Dominguez R, Gonzalez-Matos C, Lobo-Gonzalez M, Caballero- Garcia A, et al. Safety and efficacy of in-hospital clopidogrel-to-prasugrel switching in patients with acute coronary syndrome. An analysis from the ‘real world’. J Thromb Thrombolysis 2015;39:499-507.

  104. Olson WH, Ma YW, Laliberte F, Lefebvre P, Crivera C, Schein JR, et al. Prasugrel vs. clopidogrel in acute coronary syndrome patients treated with prasugrel. J Clin Pharm Ther 2014;39:663-672.

  105. Kozinski M, Obonska K, Stankowska K, Navarese EP, Fabiszak T, Stolarek W, et al. Prasugrel overcomes high on-clopidogrel platelet reactivity in the acute phase of acute coronary syndrome and maintains its antiplatelet potency at 30-day follow-up. Cardiol J 2014;21:547-556.

  106. Brandt JT, Close SL, Iturria SJ, Payne CD, Farid NA, Ernest CS, 2nd, 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.

  107. Floyd JS, Serebruany VL. Prasugrel as a potential cancer promoter: review of the unpublished data. Arch Intern Med 2010;170:1078-1080.

  108. Antman EM, Wiviott SD, Murphy SA, Voitk J, Hasin Y, Widimsky P, 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.

  109. Wiviott SD, Braunwald E, McCabe CH, Horvath I, Keltai M, Herrman JP, 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.

  110. U.S. Food & Drug Administration, Center for Drug Evaluation and Research. Aplication number 022433Orig1s000, Labeling: Brilinta™ (ticagrelor) tablets, for oral use. Maryland, Estados Unidos: 2011.

  111. Angiolillo DJ, Guzman LA. Clinical overview of promising nonthienopyridine antiplatelet agents. Am Heart J 2008;156:S23-28.

  112. Husted S, van Giezen JJ. Ticagrelor: the first reversibly binding oral P2Y12 receptor antagonist. Cardiovasc Ther 2009;27:259-274.

  113. Springthorpe B, Bailey A, Barton P, Birkinshaw TN, Bonnert RV, Brown RC, 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;17:6013-6018.

  114. van Giezen JJ, Berntsson P, Zachrisson H, Bjorkman JA. Comparison of ticagrelor and thienopyridine P2Y12 binding characteristics and antithrombotic and bleeding effects in rat and dog models of thrombosis/hemostasis. Thromb Res 2009;124:565-571.

  115. JJ VANG, Nilsson L, Berntsson P, Wissing BM, Giordanetto F, Tomlinson W, et al. Ticagrelor binds to human P2Y12 independently from ADP but antagonizes ADP-induced receptor signaling and platelet aggregation. J Thromb Haemost 2009;7:1556-1565.

  116. Wang ZY, Chen M, Zhu LL, Yu LS, Zeng S, Xiang MX, et al. Pharmacokinetic drug interactions with clopidogrel: updated review and risk management in combination therapy. Ther Clin Risk Manag 2015;11:449-467.

  117. Kalantzi KI, Tsoumani ME, Goudevenos IA, Tselepis AD. Pharmacodynamic properties of antiplatelet agents: current knowledge and future perspectives. Expert Rev Clin Pharmacol 2012;5:319-336.

  118. Patel TV, Shah JS, Patel CN. Ticagrelor: A new antiplatelet drug for acute coronary syndromes. Annals of Tropical Medicine and Public Health 2013;6:14-19.

  119. 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.

  120. Dobesh PP, Oestreich JH. Ticagrelor: pharmacokinetics, pharmacodynamics, clinical efficacy, and safety. Pharmacotherapy 2014;34:1077-1090.

  121. Teng R, Butler K. Pharmacokinetics, pharmacodynamics, tolerability and safety of single ascending doses of ticagrelor, a reversibly binding oral P2Y12 receptor antagonist, in healthy subjects. Eur J Clin Pharmacol 2010;66:487-496.

  122. Butler K, Teng R. Pharmacokinetics, pharmacodynamics, safety and tolerability of multiple ascending doses of ticagrelor in healthy volunteers. Br J Clin Pharmacol 2010;70:65-77.

  123. Tantry US, Bliden KP, Wei C, Storey RF, Armstrong M, Butler K, 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.

  124. Storey RF, Husted S, Harrington RA, Heptinstall S, Wilcox RG, Peters G, 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.

  125. Patel MR, Becker RC, Wojdyla DM, Emanuelsson H, Hiatt WR, Horrow J, et al. Cardiovascular events in acute coronary syndrome patients with peripheral arterial disease treated with ticagrelor compared with clopidogrel: Data from the PLATO Trial. Eur J Prev Cardiol 2015;22:734-742.

  126. Bonaca MP, Braunwald E, Sabatine MS. Long-term use of ticagrelor in patients with prior myocardial infarction. N Engl J Med 2015;373:1274-1275.

  127. James S, Budaj A, Aylward P, Buck KK, Cannon CP, Cornel JH, 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.

  128. Butler K, Teng R. Pharmacokinetics, pharmacodynamics, and safety of ticagrelor in volunteers with severe renal impairment. J Clin Pharmacol 2012;52:1388-1398.

  129. Mejía A, Senior JM, Ceballos M, Atehotúa S, Toro JM, Saldarriaga C, et al. Cost-effectiveness analysis of ticagrelor compared to clopidogrel for the treatment of patients with acute coronary syndrome in Colombia. Biomédica 2015;35:531-540.

  130. Björkman J-A, Kirk I, van Giezen JJ. Abstract 245: AZD6140 Inhibits Adenosine Uptake Into Erythrocytes and Enhances Coronary Blood Flow After Local Ischemia or Intracoronary Adenosine Infusion. Circulation 2007;116:II_28-II_28.

  131. Wang K, Zhou X, Huang Y, Khalil M, Wiktor D, van Giezen JJ, 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.

  132. Held C, Asenblad N, Bassand JP, Becker RC, Cannon CP, Claeys MJ, et al. Ticagrelor versus clopidogrel in patients with acute coronary syndromes undergoing coro nary artery bypass surgery: results from the PLATO (Platelet Inhibition and Patient Outcomes) trial. J Am Coll Cardiol 2011;57:672-684.

  133. Capodanno D, Angiolillo DJ. Management of antiplatelet therapy in patients with coronary artery disease requiring cardiac and noncardiac surgery. Circulation 2013;128:2785-2798.

  134. Storey RF, Bliden KP, Patil SB, Karunakaran A, Ecob R, Butler K, 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.

  135. Storey RF, Becker RC, Harrington RA, Husted S, James SK, Cools F, et al. Characterization of dyspnoea in PLATO study patients treated with ticagrelor or clopidogrel and its association with clinical outcomes. Eur Heart J 2011;32:2945-2953.

  136. Husted S, Emanuelsson H, Heptinstall S, Sandset PM, Wickens M, Peters G. 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.

  137. Cannon CP, Husted S, Harrington RA, Scirica BM, Emanuelsson H, Peters G, 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.

  138. Cattaneo M, Faioni EM. Why does ticagrelor induce dyspnea? Thromb Haemost 2012;108:1031-1036.

  139. Unlu M, Demirkol S, Yildirim AO, Balta S, Ozturk C, Iyisoy A. Atrioventricular block associated with ticagrelor therapy may require permanent pacemaker. Int J Cardiol 2016;202:946-947.

  140. Sharma M, Mascarenhas DA. Ticagrelor Associated Heart Block: The Need for Close and Continued Monitoring. Case Rep Cardiol 2017;2017:5074891.

  141. Siller-Matula JM, Jilma B. Ticagrelor: from discovery to Phase III clinical trial. Future Cardiol 2010;6:753-764.

  142. Abergel E, Nikolsky E. Ticagrelor: an investigational oral antiplatelet treatment for reduction of major adverse cardiac events in patients with acute coronary syndrome. Vasc Health Risk Manag 2010;6:963-977.

  143. Butler K, Teng R. Evaluation and characterization of the effects of ticagrelor on serum and urinary uric acid in healthy volunteers. Clin Pharmacol Ther 2012;91:264-271.

  144. Nardin M, Verdoia M, Pergolini P, Rolla R, Barbieri L, Schaffer A, et al. Serum uric acid levels during dual antiplatelet therapy with ticagrelor or clopidogrel: Results from a single-centre study. Nutr Metab Cardiovasc Dis 2016;26:567-574.

  145. Kido K, Wheeler MB, Seratnahaei A, Bailey A, Bain JA. Rhabdomyolysis precipitated by possible interaction of ticagrelor with high-dose atorvastatin. J Am Pharm Assoc (2003) 2015;55:320-323.

  146. Serebruany VL, Dinicolantonio JJ, Can MM, Pershukov IV, Kuliczkowski W. Gastrointestinal adverse events after dual antiplatelet therapy: clopidogrel is safer than ticagrelor, but prasugrel data are lacking or inconclusive. Cardiology 2013;126:35-40.

  147. Krisai P, Haschke M, Buser PT, Mueller C. Ticagrelor induced systemic inflammatory response syndrome. BMC Cardiovasc Disord 2017;17:14.

  148. Dogan A, Ozdemir B, Bal H, Ozdemir E, Kurtoglu N. Ticagrelor-associated thrombotic thrombocytopenic purpura. Anatol J Cardiol 2017;17:73-74.

  149. FDA. Kengreal™ (cangrelor) for injection, for intravenous use Initial U.S. Approval: 2015. Consultado octubre 2016, disponible en https://www.accessdata.fda.gov/ drugsatfda_docs/label/2015/204958lbl.pdf. 2015.

  150. Ferreiro JL, Ueno M, Angiolillo DJ. Cangrelor: a review on its mechanism of action and clinical development. Expert Rev Cardiovasc Ther 2009;7:1195-1201.

  151. U.S. Food & Drug Administration. Highlights of prescribing information: Kengreal™ (cangrelor) for injection, for intravenous use. 2015.

  152. Keating GM. Cangrelor: A review in percutaneous coronary intervention. Drugs 2015;75:1425-1434.

  153. Tamborini Permunian E, Riva N, Guasti L, Squizzato A. Cangrelor for the treatment of arterial thrombosis: pharmacokinetics/pharmacodynamics and clinical data. Expert Opin Drug Metab Toxicol 2015;11:625-637.

  154. Kolandaivelu K, Bhatt DL. Antiplatelet therapy in coronary heart disease prevention. Cardiol Clin 2011;29:71-85.

  155. Akers WS, Oh JJ, Oestreich JH, Ferraris S, Wethington M, Steinhubl SR. Pharmacokinetics and pharmacodynamics of a bolus and infusion of cangrelor: a direct, parenteral P2Y12 receptor antagonist. J Clin Pharmacol 2010;50:27-35.

  156. Genereux P, Stone GW, Harrington RA, Gibson CM, Steg PG, Brener SJ, et al. Impact of intraprocedural stent thrombosis during percutaneous coronary intervention: insights from the CHAMPION PHOENIX Trial (Clinical Trial Comparing Cangrelor to Clopidogrel Standard of Care Therapy in Subjects Who Require Percutaneous Coronary Intervention). J Am Coll Cardiol 2014;63:619-629.

  157. Gutierrez JA, Harrington RA, Blankenship JC, Stone GW, Steg PG, Gibson CM, et al. The effect of cangrelor and access site on ischaemic and bleeding events: insights from CHAMPION PHOENIX. Eur Heart J 2016;37:1122-1130.

  158. Harrington RA, Stone GW, McNulty S, White HD, Lincoff AM, Gibson CM, et al. Platelet inhibition with cangrelor in patients undergoing PCI. N Engl J Med 2009;361:2318-2329.

  159. Bhatt DL, Lincoff AM, Gibson CM, Stone GW, McNulty S, Montalescot G, et al. Intravenous platelet blockade with cangrelor during PCI. N Engl J Med 2009;361:2330-2341.

  160. Bonadei I, Sciatti E, Vizzardi E, D’Aloia A, Raddino R, Metra M. New frontiers in the management of acute coronary syndromes: cangrelor and elinogrel. Recent Pat Cardiovasc Drug Discov 2014;9:22-27.

  161. Bhatt DL, Stone GW, Mahaffey KW, Gibson CM, Steg PG, Hamm CW, et al. Effect of platelet inhibition with cangrelor during PCI on ischemic events. N Engl J Med 2013;368:1303-1313.

  162. Ueno M, Rao SV, Angiolillo DJ. Elinogrel: pharmacological principles, preclinical and early phase clinical testing. Future Cardiol 2010;6:445-453.

  163. Gretler D, Conley P, Andre P, Jurek M, Pandey A, Romanko K. First in human experience with PRT060128, a new direct-acting, reversible, P2Y12 inhibitor for IV and oral use. J Am Coll Cardiol. 2007;49:326A.

  164. Berger JS, Roe MT, Gibson CM, Kilaru R, Green CL, Melton L, 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 e1001.

  165. Gurbel P, Conley P, Andre P, Stephens G, Gretler DD, Jurek M. Oral dosing of PRT060128, a novel directacting, reversible P2Y12 antagonist overcomes high platelet reactivity in patients non-responsive to clopidogrel therapy. Circulation 2008;118:S972.

  166. Leonardi S, Rao SV, Harrington RA, Bhatt DL, Gibson CM, Roe MT, et al. Rationale and design of the randomized, double-blind trial testing INtraveNous and Oral administration of elinogrel, a selective and reversible P2Y12-receptor inhibitor, versus clopidogrel to eVAluate Tolerability and Efficacy in nonurgent Percutaneous Coronary Interventions patients (INNOVATE-PCI). Am Heart J 2010;160:65-72.

  167. Welsh RC, Rao SV, Zeymer U, Thompson VP, Huber K, Kochman J, et al. A randomized, double-blind, activecontrolled phase 2 trial to evaluate a novel selective and reversible intravenous and oral P2Y12 inhibitor elinogrel versus clopidogrel in patients undergoing nonurgent percutaneous coronary intervention: the INNOVATE-PCI trial. Circ Cardiovasc Interv 2012;5:336-346.

  168. Angiolillo DJ, Welsh RC, Trenk D, Neumann FJ, Conley PB, McClure MW, et al. Pharmacokinetic and pharmacodynamic effects of elinogrel: results of the platelet function substudy from the intravenous and oral administration of elinogrel to evaluate tolerability and efficacy in nonurgent percutaneous coronary intervention patients (INNOVATE- PCI) trial. Circ Cardiovasc Interv 2012;5:347-356.




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