The New Dual Antiplatelet Therapy Agents And Their Role in Acute Coronary Syndrome
Keywords:
clopidogrel, prasugrel, ticagrelor, humans, drug resistance
Abstract
Background: Prasugrel and ticagrelor are two novel antiplatelet agents, which have been subject to large randomized trials to compare their efficacy with clopidogrel for patients with acute coronary syndrome (ACS).
Aim: To conduct a systematic review of prasugrel and ticagrelor as alternative therapy to clopidogrel in patients who present with ACS undergoing PCI.
Methods: The articles cited in this paper were searched on PubMed, MEDLINE, and Plymouth University’s Metalib database. The search terms used included “dual antiplatelet therapy”, “prasugrel”, “ticagrelor”, and “clopidogrel resistance”.
Discussion: The main indications for the use of prasugrel based on current understanding are patients presenting with acute STEMI referred for primary PCI, ACS patients with DM, or those who have a high risk of stent thrombosis. Ticagrelor, on the other hand, may provide optimal benefit for patients with NSTEMI treated with conservative or invasive therapy, those with previous TIA or stroke, advanced age, or small body surface.
Conclusion: Prasugrel and ticagrelor have been shown to be adequate P2Y12 antiplatelet therapy alternatives to clopidogrel in the management of patients with ACS. While prasugrel and ticagrelor have both been shown to clinically improve platelet inhibition and significantly reduce the incidence of stent thrombosis compared with clopidogrel therapy, both increase the risk of a significant bleeding incident. Both ticagrelor and prasugrel have been shown to be appropriate and effective treatment alternatives for ACS patients who display clopidogrel treatment resistance or failure.
References
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4. Serebruany VL, Steinhubl SR, Berger PB, Malinin AI, Bhatt DL, Topol EJ. Variability in platelet responsiveness to clopidogrel among 544 individuals. J Am Coll Cardiol. 2005 Jan 18;45(2):246-51. DOI: 10.1016/j.jacc.2004.09.067.
5. Simon T, Verstuyft C, Mary-Krause M, Quteineh L, Drouet E, Méneveau N, et al. Genetic deter¬minants of response to clopidogrel and cardiovascular events. N Engl J Med. 2009 Jan 22;360(4):363-75. DOI: 10.1056/NEJMoa0808227.
6. Tentzeris I, Siller-Matula J, Farhan S, Jarai R, Wojta J, Huber K. Platelet function variability and non-genetic causes. Thromb Haemost. 2011 May;105 Suppl 1:S60-6. DOI: 10.1160/THS11-01-0025.
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8. Angiolillo DJ, Capranzano P. Pharmacology of emerging novel platelet inhibitors. Am Heart J. 2008 Aug;156(2 Suppl):S10-5. DOI: 10.1016/j.ahj.2008.06.004.
9. Wiviott SD, Braunwald E, McCabe CH, Montalescot G, Ruzyllo W, Gottlieb S, et al. Prasugrel ver¬sus clopidogrel in patients with acute coronary syndromes. N Engl J Med. 2007 Nov 15;357(20):2001-15. DOI: 10.1056/NEJMoa0706482.
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11. Angiolillo DJ, Guzman LA. Clinical overview of promising nonthienopyridine antiplatelet agents. Am Heart J. 2008 Aug;156(2 Suppl):S23-8. DOI: 10.1016/j.ahj.2008.06.006.
12. Wallentin L, James S, Storey RF, Armstrong M, Barratt BJ, Horrow J, 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 Oct 16;376(9749):1320-8. DOI: 10.1016/S0140-6736(10)61274-3.
13. 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 Sep 10;361(11):1045-57. DOI: 10.1056/NEJMoa0904327.
14. James SK, Roe MT, Cannon CP, Cornel JH, Horrow J, Husted S, et al. Ticagrelor versus clopidogrel in patients with acute coronary syndromes intended for non-invasive management: Substudy from prospective randomised PLATelet inhibition and patient Outcomes (PLATO) trial. BMJ. 2011 Jun 17;342:d3527. DOI: 10.1136/bmj.d3527.
15. Held C, Asenblad N, Bassand JP, Becker RC, Cannon CP, Claeys MJ, 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 Feb 8;57(6):672-84. DOI: 10.1016/j.jacc.2010.10.029.
16. 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 Jul 13;56(3):185-93. DOI: 10.1016/j.jacc.2010.01.062.
17. Gresele P, Arnout J, Deckmyn H, Vermylen J. Mechanism of the antiplatelet action of dipyridamole in whole blood: modulation of adenosine concentration and activity. Thromb Haemost.1986 Feb 28;55(1):12-8.
18. Björkman JA, Kirk I, van Giezen JJ. AZD6140 inhibits adenosine uptake into erythrocytes and enhances coronary blood flow after local ischemia or intracoronary adenosine infusion (abstr). Circulation. 2007;116:II28.
19. Burki NK, Dale WJ, Lee LY. Intravenous adenosine and dyspnea in humans. J Appl Physiol. 2005 Jan;98(1):180-85.
20. DiMarco JP, Sellers TD, Berne RM, West GA, Berladinelli L. Adenosine: electrophysiologic effects and therapeutic use for terminating paroxysmal supraventricular yachycardia. Circulation. 1983 Dec;68(6):1254-63. DOI: 10.1161/01.CIR.68.6.1254.
21. James S, Budaj A, Aylward P, Buck KK, Cannon CP, Cornel JH, et al. Ticagrelor versus clopi¬dogrel in acute coronary syndromes in relation to renal func¬tion: results from the Platelet Inhibition and Patient Outcomes (PLATO) trial. Circulation. 2010 Sep 14;122(11):1056-67. DOI: 10.1161/CIRCULATIONAHA.109.933796.
22. Wijns W, Kolh P, Danchin N, Di Mario C, Falk V, Folliguet T, et al. Guidelines on myocardial revascularization: the task force on myocardial revascularization of the European Society of Cardiology (ESC) and the European Association for Cardio-Thoracic Surgery (EACTS). Eur Heart J. 2010 Oct;31(20):2501-55. DOI: 10.1093/eurheartj/ehq277.
23. National Institute for Health and Care Excellence. Prasugrel for the Treatment of Acute Coronary Syndromes with Percutaneous Coronary Intervention (TA182). London, UK: National Institute for Health and Care Excellence; October 2009.
24. Curzen, N. Antiplatelet therapy in acute coronary syndromes: beyond aspirin and clopidogrel. Heart. 2012 Nov;98(22):1617-9. DOI: 10.1136/heartjnl-2012-302299.
25. National Institute for Health and Care Excellence. Ticagrelor for the Treatment of Acute Coronary Syndromes (TA236). London, UK: National Institute for Health and Care Excellence; October 2011.
26. Steg PG, James S, Harrington RA, Ardissino D, Becker RC, Cannon CP, et al. Ticagrelor versus clopidogrel in patients with ST-elevation acute coronary syndromes intended for reperfusion with primary percutaenous coronary intervention. A Platelet Inhibition and Patient Outcomes (PLATO) trial subgroup analysis. Circulation. 2010 Nov 23;122(21):2131-41. DOI: 10.1161/CIRCULATIONAHA.109.927582.
27. Mahaffey KW, Wojdyla DM, Caroll K, Becker RC, Storey RF, Angiolillo DJ, et al. Ticagrelor compared with clopidogrel by geographic region in the platelet inhibition and patient outcomes (PLATO) trial. Circulation. 2011 Aug 2;124(5):544-54. DOI: 10.1161/CIRCULATIONAHA.111.047498.
28. Kohli P, Udell JA, Murphy SA, Cannon CP, Antman EM, Braunwald E, et al. Discharge aspirin dose and clinical outcomes in patients with acute coronary syndromes treated with prasugrel versus clopidogrel: an analysis from the TRITON-TIMI 38 Study (Trial to Assess Improvememnt in Therapeutic Outcomes by Optimizing Platelet Inhibition With Prasugrel-Thrombolysis In Myocardial Infarction 38). J Am Coll Cardiol. 2014 Jan 28;63(3):225-32. DOI: 10.1016/j.jacc.2013.09.023.
29. FitzGerald GA, Oates JA, Hawiger J, Maas RL, Roberts LJ 2nd, Lawson JA, et al. Endogenous biosynthesis of prostacyclin and thromboxane and platelet function during chronic administration of aspirin in man. J Clin Invest. 1983 Mar;71(3):676-88. DOI: 10.1172/JCI110814.
30. Cattaneo M, Lecchi A. Inhibition of the platelet P2Y12 receptor for adenosine diphosphate potentiates the antiplatelet effect of prostacyclin. J Thromb Haemost. 2007 Mar;5(3):577-82.
31. Floyd JS, Serebruany VL. Prasugrel as a potential cancer promoter: review of the unpublished data. Arch Intern Med. 2010 Jun 28;170(12):1078-80. DOI: 10.1001/archinternmed.2010.154.
2. 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 Dec;32(23):2999-3054. DOI: 10.1016/j.jpeds.2013.07.019.
3. Jneid H, Anderson JL, Wright RS, Adams CD, Bridges CR, Casey DE Jr, et al. 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). Circulation. 2012 Aug 14;126(7):875-910. DOI: 10.1161/CIR.0b013e318256f1e0.
4. Serebruany VL, Steinhubl SR, Berger PB, Malinin AI, Bhatt DL, Topol EJ. Variability in platelet responsiveness to clopidogrel among 544 individuals. J Am Coll Cardiol. 2005 Jan 18;45(2):246-51. DOI: 10.1016/j.jacc.2004.09.067.
5. Simon T, Verstuyft C, Mary-Krause M, Quteineh L, Drouet E, Méneveau N, et al. Genetic deter¬minants of response to clopidogrel and cardiovascular events. N Engl J Med. 2009 Jan 22;360(4):363-75. DOI: 10.1056/NEJMoa0808227.
6. Tentzeris I, Siller-Matula J, Farhan S, Jarai R, Wojta J, Huber K. Platelet function variability and non-genetic causes. Thromb Haemost. 2011 May;105 Suppl 1:S60-6. DOI: 10.1160/THS11-01-0025.
7. Mega JL, Hochholzer W, Frelinger AL 3rd, Kluk MJ, Angiolillo DJ, Kereiakes DJ, et al. Dosing clopidogrel based on CYP2C19 genotype and the effect on platelet reactivity in patients with stable cardiovascular dis¬ease. JAMA. 2011 Nov 23;306(20):2221-28. DOI: 10.1001/jama.2011.1703.
8. Angiolillo DJ, Capranzano P. Pharmacology of emerging novel platelet inhibitors. Am Heart J. 2008 Aug;156(2 Suppl):S10-5. DOI: 10.1016/j.ahj.2008.06.004.
9. Wiviott SD, Braunwald E, McCabe CH, Montalescot G, Ruzyllo W, Gottlieb S, et al. Prasugrel ver¬sus clopidogrel in patients with acute coronary syndromes. N Engl J Med. 2007 Nov 15;357(20):2001-15. DOI: 10.1056/NEJMoa0706482.
10. Wiviott SD, Braunwald E, Angiolillo DJ, Meisel S, Dalby AJ, Verggheut FW, et al. Greater clinical benefit of more intensive oral antiplatelet therapy with prasu¬grel in patients with diabetes mellitus in the trial to assess improvement in therapeutic outcomes by optimizing plate¬let inhibition with prasugrel − Thrombolysis in Myocardial Infarction 38. Circulation. 2008 Oct 14;118(16):1626-36. DOI: 10.1161/CIRCULATIONAHA.108.791061.
11. Angiolillo DJ, Guzman LA. Clinical overview of promising nonthienopyridine antiplatelet agents. Am Heart J. 2008 Aug;156(2 Suppl):S23-8. DOI: 10.1016/j.ahj.2008.06.006.
12. Wallentin L, James S, Storey RF, Armstrong M, Barratt BJ, Horrow J, 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 Oct 16;376(9749):1320-8. DOI: 10.1016/S0140-6736(10)61274-3.
13. 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 Sep 10;361(11):1045-57. DOI: 10.1056/NEJMoa0904327.
14. James SK, Roe MT, Cannon CP, Cornel JH, Horrow J, Husted S, et al. Ticagrelor versus clopidogrel in patients with acute coronary syndromes intended for non-invasive management: Substudy from prospective randomised PLATelet inhibition and patient Outcomes (PLATO) trial. BMJ. 2011 Jun 17;342:d3527. DOI: 10.1136/bmj.d3527.
15. Held C, Asenblad N, Bassand JP, Becker RC, Cannon CP, Claeys MJ, 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 Feb 8;57(6):672-84. DOI: 10.1016/j.jacc.2010.10.029.
16. 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 Jul 13;56(3):185-93. DOI: 10.1016/j.jacc.2010.01.062.
17. Gresele P, Arnout J, Deckmyn H, Vermylen J. Mechanism of the antiplatelet action of dipyridamole in whole blood: modulation of adenosine concentration and activity. Thromb Haemost.1986 Feb 28;55(1):12-8.
18. Björkman JA, Kirk I, van Giezen JJ. AZD6140 inhibits adenosine uptake into erythrocytes and enhances coronary blood flow after local ischemia or intracoronary adenosine infusion (abstr). Circulation. 2007;116:II28.
19. Burki NK, Dale WJ, Lee LY. Intravenous adenosine and dyspnea in humans. J Appl Physiol. 2005 Jan;98(1):180-85.
20. DiMarco JP, Sellers TD, Berne RM, West GA, Berladinelli L. Adenosine: electrophysiologic effects and therapeutic use for terminating paroxysmal supraventricular yachycardia. Circulation. 1983 Dec;68(6):1254-63. DOI: 10.1161/01.CIR.68.6.1254.
21. James S, Budaj A, Aylward P, Buck KK, Cannon CP, Cornel JH, et al. Ticagrelor versus clopi¬dogrel in acute coronary syndromes in relation to renal func¬tion: results from the Platelet Inhibition and Patient Outcomes (PLATO) trial. Circulation. 2010 Sep 14;122(11):1056-67. DOI: 10.1161/CIRCULATIONAHA.109.933796.
22. Wijns W, Kolh P, Danchin N, Di Mario C, Falk V, Folliguet T, et al. Guidelines on myocardial revascularization: the task force on myocardial revascularization of the European Society of Cardiology (ESC) and the European Association for Cardio-Thoracic Surgery (EACTS). Eur Heart J. 2010 Oct;31(20):2501-55. DOI: 10.1093/eurheartj/ehq277.
23. National Institute for Health and Care Excellence. Prasugrel for the Treatment of Acute Coronary Syndromes with Percutaneous Coronary Intervention (TA182). London, UK: National Institute for Health and Care Excellence; October 2009.
24. Curzen, N. Antiplatelet therapy in acute coronary syndromes: beyond aspirin and clopidogrel. Heart. 2012 Nov;98(22):1617-9. DOI: 10.1136/heartjnl-2012-302299.
25. National Institute for Health and Care Excellence. Ticagrelor for the Treatment of Acute Coronary Syndromes (TA236). London, UK: National Institute for Health and Care Excellence; October 2011.
26. Steg PG, James S, Harrington RA, Ardissino D, Becker RC, Cannon CP, et al. Ticagrelor versus clopidogrel in patients with ST-elevation acute coronary syndromes intended for reperfusion with primary percutaenous coronary intervention. A Platelet Inhibition and Patient Outcomes (PLATO) trial subgroup analysis. Circulation. 2010 Nov 23;122(21):2131-41. DOI: 10.1161/CIRCULATIONAHA.109.927582.
27. Mahaffey KW, Wojdyla DM, Caroll K, Becker RC, Storey RF, Angiolillo DJ, et al. Ticagrelor compared with clopidogrel by geographic region in the platelet inhibition and patient outcomes (PLATO) trial. Circulation. 2011 Aug 2;124(5):544-54. DOI: 10.1161/CIRCULATIONAHA.111.047498.
28. Kohli P, Udell JA, Murphy SA, Cannon CP, Antman EM, Braunwald E, et al. Discharge aspirin dose and clinical outcomes in patients with acute coronary syndromes treated with prasugrel versus clopidogrel: an analysis from the TRITON-TIMI 38 Study (Trial to Assess Improvememnt in Therapeutic Outcomes by Optimizing Platelet Inhibition With Prasugrel-Thrombolysis In Myocardial Infarction 38). J Am Coll Cardiol. 2014 Jan 28;63(3):225-32. DOI: 10.1016/j.jacc.2013.09.023.
29. FitzGerald GA, Oates JA, Hawiger J, Maas RL, Roberts LJ 2nd, Lawson JA, et al. Endogenous biosynthesis of prostacyclin and thromboxane and platelet function during chronic administration of aspirin in man. J Clin Invest. 1983 Mar;71(3):676-88. DOI: 10.1172/JCI110814.
30. Cattaneo M, Lecchi A. Inhibition of the platelet P2Y12 receptor for adenosine diphosphate potentiates the antiplatelet effect of prostacyclin. J Thromb Haemost. 2007 Mar;5(3):577-82.
31. Floyd JS, Serebruany VL. Prasugrel as a potential cancer promoter: review of the unpublished data. Arch Intern Med. 2010 Jun 28;170(12):1078-80. DOI: 10.1001/archinternmed.2010.154.
Published
29-Nov-2014
How to Cite
Williams, G. (2014). The New Dual Antiplatelet Therapy Agents And Their Role in Acute Coronary Syndrome. Res Medica, 22(1), 51-63. https://doi.org/10.2218/resmedica.v22i1.811
Section
Clinical Review Article
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