Display options
Share it on

Postepy Kardiol Interwencyjnej. 2015;11(4):259-80. doi: 10.5114/pwki.2015.55596. Epub 2015 Jan 12.

Personalized antiplatelet therapy with P2Y12 receptor inhibitors: benefits and pitfalls.

Postepy w kardiologii interwencyjnej = Advances in interventional cardiology

Max-Paul Winter, Marek Koziński, Jacek Kubica, Daniel Aradi, Jolanta M Siller-Matula

Affiliations

  1. Department of Cardiology, Medical University of Vienna, Vienna, Austria.
  2. Department of Cardiology and Internal Medicine, Collegium Medicum of the Nicolaus Copernicus University, Bydgoszcz, Poland.
  3. Department of Cardiology, Heart Center Balatonfüred and Semmelweis University, Heart and Vascular Center, Budapest, Hungary.

PMID: 26677375 PMCID: PMC4679793 DOI: 10.5114/pwki.2015.55596

Abstract

Antiplatelet therapy with P2Y12 receptor inhibitors has become the cornerstone of medical treatment in patients with acute coronary syndrome, after percutaneous coronary intervention and in secondary prevention of atherothrombotic events. Clopidogrel used to be the most broadly prescribed P2Y12 receptor inhibitor with undisputable benefits especially in combination with aspirin, but a considerable number of clopidogrel-treated patients experience adverse thrombotic events in whom insufficient P2Y12-inhibition and a consequential high on-treatment platelet reactivity is a common finding. This clinically relevant limitation of clopidogrel has driven the increased use of new antiplatelet agents. Prasugrel (a third generation thienopyridine) and ticagrelor (a cyclopentyl-triazolo-pyrimidine) feature more potent and predictable P2Y12-inhibition compared to clopidogrel, which translates into improved ischemic outcomes. However, excessive platelet inhibition and consequential low on-treatment platelet reactivity comes at the price of increased risk of major bleeding. The majority of randomized clinical trials failed to demonstrate improved clinical outcomes with platelet function testing and tailored antiplatelet therapy, but results of all recent trials of potent antiplatelets and prolonged antiplatelet durations point towards a need for individualized antiplatelet approach in order to decrease thrombotic events without increasing bleeding. This review focuses on potential strategies for personalizing antiplatelet treatment.

Keywords: P2Y12 receptor inhibitors; acute coronary syndromes; antiplatelet therapy; platelet reactivity

References

  1. Circ Cardiovasc Genet. 2011 Aug 1;4(4):429-36 - PubMed
  2. Cardiol Res Pract. 2013;2013:195456 - PubMed
  3. Eur Heart J. 2015 Jul 14;36(27):1762-71 - PubMed
  4. Transfusion. 2007 Jan;47(1):103-6 - PubMed
  5. J Thromb Haemost. 2014 Jan;12(1):2-13 - PubMed
  6. J Thromb Haemost. 2010 Feb;8(2):351-9 - PubMed
  7. Thromb Haemost. 2013 Oct;110(4):628-31 - PubMed
  8. Blood Coagul Fibrinolysis. 1996 Jun;7(4):459-64 - PubMed
  9. J Am Coll Cardiol. 2008 Sep 30;52(14):1128-33 - PubMed
  10. Thromb Haemost. 2001 Jul;86(1):222-32 - PubMed
  11. Thromb Haemost. 2003 Nov;90(5):863-71 - PubMed
  12. J Am Coll Cardiol. 2010 Jul 20;56(4):317-8 - PubMed
  13. J Thromb Haemost. 2009 Aug;7(8):1409-11 - PubMed
  14. J Am Coll Cardiol. 2012 Jul 17;60(3):193-9 - PubMed
  15. Thromb Res. 2013 Jul;132(1):e36-41 - PubMed
  16. Fundam Clin Pharmacol. 2012 Feb;26(1):39-46 - PubMed
  17. Diabetologia. 2001 Feb;44(2):188-95 - PubMed
  18. J Thromb Haemost. 2008 Oct;6(10):1824-6 - PubMed
  19. Biomark Med. 2011 Feb;5(1):31-42 - PubMed
  20. Thromb Haemost. 2013 Oct;110(4):769-76 - PubMed
  21. Pharmacogenet Genomics. 2012 Mar;22(3):169-75 - PubMed
  22. J Lab Clin Med. 2004 May;143(5):301-9 - PubMed
  23. J Thromb Haemost. 2010 Dec;8(12):2624-41 - PubMed
  24. Lancet. 2009 Jan 24;373(9660):309-17 - PubMed
  25. JACC Cardiovasc Interv. 2013 Aug;6(8):854-63 - PubMed
  26. J Am Coll Cardiol. 2005 Jun 7;45(11):1748-52 - PubMed
  27. J Thromb Haemost. 2007 Jul;5 Suppl 1:230-7 - PubMed
  28. Platelets. 2009 Mar;20(2):125-30 - PubMed
  29. Circulation. 2010 Feb 2;121(4):512-8 - PubMed
  30. J Am Coll Cardiol. 2014 Feb 25;63(7):630-5 - PubMed
  31. Eur Heart J. 2010 Dec;31(24):2974-6 - PubMed
  32. Circulation. 2004 Jun 29;109 (25):3171-5 - PubMed
  33. J Thromb Haemost. 2007 Aug;5(8):1630-6 - PubMed
  34. J Am Coll Cardiol. 2007 Apr 10;49(14):1505-16 - PubMed
  35. J Cardiovasc Pharmacol Ther. 2012 Jun;17(2):164-72 - PubMed
  36. Eur Heart J. 2010 Jan;31(1):59-66 - PubMed
  37. Eur Heart J. 2012 Sep;33(17 ):2143-50 - PubMed
  38. Thromb Haemost. 2015 Jan;113(1):37-52 - PubMed
  39. JAMA. 2011 Oct 26;306(16):1765-74 - PubMed
  40. Diabetes. 2007 Feb;56(2):462-7 - PubMed
  41. Thromb Haemost. 1993 Dec 20;70(6):1030-6 - PubMed
  42. Int J Cardiol. 2013 Jul 31;167(2):430-5 - PubMed
  43. J Thromb Haemost. 2010 Feb;8(2):250-6 - PubMed
  44. QJM. 2011 Jul;104(7):561-9 - PubMed
  45. Nature. 2014 May 1;509(7498):115-8 - PubMed
  46. Circulation. 2003 Aug 26;108(8):989-95 - PubMed
  47. Am J Cardiol. 2008 Jun 15;101(12):1700-3 - PubMed
  48. JAMA. 2009 Aug 26;302(8):849-57 - PubMed
  49. J Thromb Haemost. 2011 Dec;9(12):2379-85 - PubMed
  50. Thromb Haemost. 2013 May;109(5):792-8 - PubMed
  51. JACC Cardiovasc Interv. 2008 Dec;1(6):649-53 - PubMed
  52. J Thromb Haemost. 2008 Jan;6(1):54-61 - PubMed
  53. Eur Heart J. 2016 Jan 14;37(3):245-52 - PubMed
  54. J Thromb Haemost. 2006 Dec;4(12):2547-52 - PubMed
  55. J Am Coll Cardiol. 2011 Jul 26;58(5):467-73 - PubMed
  56. Med Sci Monit. 2009 Dec;15(12):MS24-30 - PubMed
  57. Resuscitation. 2014 May;85(5):649-56 - PubMed
  58. Platelets. 2015;26(1):53-8 - PubMed
  59. J Am Coll Cardiol. 2009 Feb 24;53(8):648-57 - PubMed
  60. CMAJ. 2006 Jun 6;174(12):1715-22 - PubMed
  61. Acta Anaesthesiol Scand. 2009 Feb;53(2):168-75 - PubMed
  62. Nat Med. 2011 Jan;17(1):110-6 - PubMed
  63. Stroke. 2005 Jul;36(7):1394-9 - PubMed
  64. J Am Coll Cardiol. 2005 Nov 15;46(10):1820-6 - PubMed
  65. J Cardiol. 2011 Mar;57(2):194-201 - PubMed
  66. J Am Coll Cardiol. 2011 Dec 13;58(25):2630-9 - PubMed
  67. J Am Coll Cardiol. 2013 Dec 17;62(24):2261-73 - PubMed
  68. AJNR Am J Neuroradiol. 2008 Apr;29(4):786-91 - PubMed
  69. Eur Heart J. 2010 Dec;31(24):3046-53 - PubMed
  70. Thromb Haemost. 2011 Aug;106(2):230-9 - PubMed
  71. Am J Hematol. 1991 Aug;37(4):239-42 - PubMed
  72. Thromb Res. 2012 Jul;130(1):65-9 - PubMed
  73. Thromb Haemost. 2007 Dec;98 (6):1329-34 - PubMed
  74. Am Heart J. 2009 Jan;157(1):148.e1-5 - PubMed
  75. Arterioscler Thromb Vasc Biol. 2006 Feb;26(2):417-22 - PubMed
  76. Br J Pharmacol. 2010 Feb 1;159(3):502-17 - PubMed
  77. Am Heart J. 2011 Oct;162(4):733-9 - PubMed
  78. J Am Coll Cardiol. 2010 Jun 1;55(22):2427-34 - PubMed
  79. Am Heart J. 2010 May;159(5):891-898.e1 - PubMed
  80. Cardiovasc Ther. 2012 Aug;30(4):e174-82 - PubMed
  81. Circulation. 2009 Dec 1;120(22):2214-21 - PubMed
  82. J Am Coll Cardiol. 2008 May 20;51(20):1925-34 - PubMed
  83. Am J Physiol Heart Circ Physiol. 2001 Apr;280(4):H1480-9 - PubMed
  84. Eur Heart J. 2011 Jul;32(13):1605-13 - PubMed
  85. J Am Coll Cardiol. 2006 Jul 18;48(2):298-304 - PubMed
  86. Thromb Haemost. 2008 Feb;99(2):409-15 - PubMed
  87. Catheter Cardiovasc Interv. 2003 Jul;59(3):295-302 - PubMed
  88. Am J Cardiol. 2009 Oct 15;104(8):1078-82 - PubMed
  89. J Am Coll Cardiol. 2009 Sep 22;54(13):1149-53 - PubMed
  90. Curr Med Res Opin. 2014 May;30(5):813-28 - PubMed
  91. J Am Coll Cardiol. 2012 Jun 12;59(24):2159-64 - PubMed
  92. N Engl J Med. 2007 Dec 13;357(24):2482-94 - PubMed
  93. N Engl J Med. 2009 Jan 22;360(4):354-62 - PubMed
  94. Am J Cardiol. 2009 Mar 15;103(6):806-11 - PubMed
  95. Cardiol J. 2014;21(5):458-64 - PubMed
  96. J Am Coll Cardiol. 2009 Mar 10;53(10):849-56 - PubMed
  97. J Am Coll Cardiol. 2007 Oct 16;50(16):1541-7 - PubMed
  98. J Am Coll Cardiol. 2007 Feb 13;49(6):657-66 - PubMed
  99. Lancet. 2010 Oct 16;376(9749):1320-8 - PubMed
  100. Eur Heart J. 2007 Aug;28(15):1814-9 - PubMed
  101. Lancet. 2010 Oct 16;376(9749):1312-9 - PubMed
  102. Circ Cardiovasc Interv. 2011 Oct 1;4(5):422-8 - PubMed
  103. EuroIntervention. 2009 Aug;5(3):325-9 - PubMed
  104. Platelets. 2008 Dec;19(8):595-604 - PubMed
  105. Int J Cardiol. 2013 Sep 1;167(5):2018-23 - PubMed
  106. Thromb Haemost. 2008 Jan;99(1):161-8 - PubMed
  107. Ann Thorac Surg. 2011 Jan;91(1):123-9 - PubMed
  108. Stroke. 2014 Feb;45(2):492-503 - PubMed
  109. N Engl J Med. 2012 Nov 29;367(22):2100-9 - PubMed
  110. Circulation. 2009 Jun 30;119(25):3215-22 - PubMed
  111. N Engl J Med. 2009 Sep 10;361(11):1045-57 - PubMed
  112. Eur J Intern Med. 2011 Oct;22(5):471-7 - PubMed
  113. Thromb Res. 2006;118(4):487-93 - PubMed
  114. Heart. 2011 Jun;97(12):983-90 - PubMed
  115. J Thromb Haemost. 2012 Oct;10(10):1999-2005 - PubMed
  116. Drugs. 2012 Nov 12;72(16):2087-116 - PubMed
  117. Nat Rev Cardiol. 2016 Jan;13(1):11-27 - PubMed
  118. J Am Coll Cardiol. 2013 Apr 16;61(15):1601-6 - PubMed
  119. Platelets. 2015;26(1):43-7 - PubMed
  120. N Engl J Med. 2010 Oct 28;363(18):1704-14 - PubMed
  121. Kardiol Pol. 2009 Aug;67(8):827-34 - PubMed
  122. JAMA. 2010 Feb 24;303(8):754-62 - PubMed
  123. J Am Soc Nephrol. 2011 Apr;22(4):627-33 - PubMed
  124. JAMA. 2011 Mar 16;305(11):1097-105 - PubMed
  125. J Thromb Haemost. 2011 Oct;9(10):2106-8 - PubMed
  126. Eur Heart J. 2009 Jul;30(14):1753-63 - PubMed
  127. Thromb Res. 2010 Aug;126(2):e147-9 - PubMed
  128. J Am Coll Cardiol. 2008 Jan 22;51(3):256-60 - PubMed
  129. Circulation. 2009 Jan 20;119(2):237-42 - PubMed
  130. Thromb Haemost. 2013 Nov;110(5):876-87 - PubMed
  131. Eur Heart J Acute Cardiovasc Care. 2015 May 5;:null - PubMed
  132. Circulation. 2001 Dec 4;104(23):2767-71 - PubMed
  133. Thromb Haemost. 2013 Mar;109(3):550-5 - PubMed
  134. Eur J Clin Invest. 1982 Oct;12(5):395-8 - PubMed
  135. Nat Clin Pract Cardiovasc Med. 2008 Dec;5(12):766-80 - PubMed
  136. Eur Heart J. 2005 Apr;26(7):650-61 - PubMed
  137. Thromb Haemost. 2014 Aug;112(2):224-42 - PubMed
  138. Clin Pharmacol Ther. 2011 Oct;90(4):561-7 - PubMed
  139. Thromb Res. 2009 May;124(1):46-51 - PubMed
  140. Thromb Haemost. 2007 Feb;97(2):282-7 - PubMed
  141. Platelets. 2008 Aug;19(5):335-41 - PubMed
  142. J Am Coll Cardiol. 2011 Jun 28;58(1):30-9 - PubMed
  143. Circulation. 2005 Mar 8;111(9):1153-9 - PubMed
  144. Br J Clin Pharmacol. 2007 Apr;63(4):421-30 - PubMed
  145. Thromb Haemost. 2010 Jun;103(6):1245-53 - PubMed
  146. Circ J. 2011;75(1):99-105 - PubMed
  147. Circulation. 2003 Jun 17;107(23):2908-13 - PubMed
  148. Hypertension. 1996 Aug;28(2):209-12 - PubMed
  149. Eur J Pharmacol. 2014 Nov 5;742:47-54 - PubMed
  150. Eur Heart J. 2006 Oct;27(20):2420-5 - PubMed
  151. PLoS One. 2015 Mar 23;10(3):e0121620 - PubMed
  152. JAMA. 2012 Nov 7;308(17):1785-94 - PubMed
  153. Arterioscler Thromb Vasc Biol. 2008 Mar;28(3):403-12 - PubMed
  154. PLoS One. 2014 Jul 22;9(7):e102701 - PubMed
  155. Nat Rev Cardiol. 2015 Jan;12(1):30-47 - PubMed
  156. Blood. 2007 Dec 15;110(13):4243-52 - PubMed
  157. Clin Pharmacokinet. 2012 May 1;51(5):305-18 - PubMed
  158. Thromb Haemost. 2008 Jan;99(1):121-6 - PubMed
  159. Platelets. 2011;22(8):579-87 - PubMed
  160. Circ Cardiovasc Interv. 2011 Dec 1;4(6):585-94 - PubMed
  161. J Thromb Haemost. 2006 Mar;4(3):542-9 - PubMed
  162. Am J Cardiol. 2009 Jan 1;103(1):5-10 - PubMed
  163. Thromb Haemost. 2007 Mar;97(3):385-93 - PubMed
  164. Platelets. 2014;25(7):506-12 - PubMed
  165. J Thromb Haemost. 2012 Apr;10 (4):529-42 - PubMed
  166. Int J Cardiol. 2013 Sep 1;167(5):2140-8 - PubMed
  167. Atherosclerosis. 2010 Nov;213(1):256-62 - PubMed
  168. J Am Coll Cardiol. 2005 Nov 15;46(10):1827-32 - PubMed
  169. BMC Med. 2011 Jan 12;9:3 - PubMed
  170. J Thorac Cardiovasc Surg. 2004 Sep;128(3):425-31 - PubMed
  171. Int J Cardiol. 2013 Dec 10;170(2):e21-2 - PubMed
  172. Eur Heart J. 2009 Apr;30(8):916-22 - PubMed
  173. J Am Coll Cardiol. 2008 Apr 8;51(14):1404-11 - PubMed
  174. Am Heart J. 2010 Sep;160(3):506-12 - PubMed
  175. J Thromb Haemost. 2011 Oct;9(10 ):1892-901 - PubMed
  176. J Am Coll Cardiol. 2007 Jun 19;49(24):2312-7 - PubMed
  177. J Am Coll Cardiol. 2011 Jun 21;57(25):2474-83 - PubMed
  178. J Am Coll Cardiol. 2006 Nov 7;48(9):1742-50 - PubMed
  179. J Am Coll Cardiol. 2006 Jan 3;47(1):27-33 - PubMed
  180. Rev Esp Cardiol (Engl Ed). 2012 Mar;65(3):219-26 - PubMed
  181. JAMA. 2011 Nov 23;306(20):2221-8 - PubMed
  182. J Am Coll Cardiol. 2014 Apr 22;63(15):1500-9 - PubMed
  183. J Thromb Haemost. 2007 Jul;5(7):1545-51 - PubMed
  184. Thromb Haemost. 2010 May;103(5):920-5 - PubMed
  185. Diabetes Care. 2009 Apr;32(4):531-40 - PubMed
  186. Eur Heart J. 2008 Apr;29(8):992-1000 - PubMed
  187. Heart. 2012 Jan;98 (2):139-44 - PubMed
  188. BMJ Open. 2014 Oct 31;4(10):e005781 - PubMed
  189. Cardiol J. 2014;21(5):547-56 - PubMed
  190. BMJ. 1997 May 24;314(7093):1512-5 - PubMed
  191. Ann Intern Med. 1998 Sep 1;129(5):394-405 - PubMed
  192. Diabetes Care. 2001 Aug;24(8):1476-85 - PubMed
  193. QJM. 2013 Feb;106(2):105-15 - PubMed
  194. JACC Cardiovasc Interv. 2013 Nov;6(11):1111-28 - PubMed
  195. N Engl J Med. 2007 Nov 15;357(20):2001-15 - PubMed
  196. Cardiology. 2010;117(2):81-7 - PubMed
  197. Circ Cardiovasc Interv. 2012 Dec;5(6):797-804 - PubMed
  198. J Lab Clin Med. 2001 Sep;138(3):152-63 - PubMed
  199. J Am Coll Cardiol. 2014 Sep 9;64(10):1005-14 - PubMed
  200. Circulation. 2011 Feb 22;123(7):798-813 - PubMed
  201. J Am Coll Cardiol. 2012 Aug 14;60(7):645-81 - PubMed
  202. J Am Coll Cardiol. 2008 Nov 4;52(19):1557-63 - PubMed
  203. Biochem Biophys Res Commun. 2012 Feb 24;418(4):754-8 - PubMed
  204. Thromb Haemost. 2007 Oct;98(4):838-43 - PubMed
  205. Circ Cardiovasc Interv. 2012 Feb 1;5(1):82-8, S1-2 - PubMed
  206. Cardiol J. 2009;16(6):535-44 - PubMed
  207. N Engl J Med. 2009 Jan 22;360(4):363-75 - PubMed
  208. Clin Sci (Lond). 2015 Jan;128(2):121-30 - PubMed
  209. Am J Cardiol. 2012 Jan 15;109(2):214-8 - PubMed
  210. J Clin Invest. 2004 Feb;113(3):340-5 - PubMed
  211. J Am Coll Cardiol. 2008 Aug 26;52(9):734-9 - PubMed

Publication Types