Background. Acute Coronary Syndrome (ACS) is a clinical condition encompassing ST Segment Elevation Myocardial Infarction (STEMI), Non-ST Segment Elevation Myocardial Infarction (NSTEMI), and Unstable Angina (UA) and is characterized by ruptured coronary plaque, ischemic stress, and/or myocardial injury. Emergency department (ED) physicians are on the front lines of ACS management. The role of new antiplatelet agents ticagrelor and prasugrel in acute ED management of ACS has not yet been defined. Objective. To critically review clinical trials using ticagrelor and prasugrel in the treatment of ACS and inform practitioners of their potential utility in treating ACS in the ED. Results. Trials on the efficacy of ticagrelor and prasugrel achieve statistical significance in decreasing composite endpoints in select patient populations. Conclusion. The use of ticagrelor and prasugrel as first line ED treatment of ACS is not well established. Current evidence supports the use of several agents with the final decision based on treatment protocols conjointly developed between cardiology and emergency medicine (EM). Further clinical trials involving head-to-head trials or comparisons of drug-based strategies are required to show superiority in reducing cardiac endpoints with regard to ED initiation of treatment. 1. Introduction Acute Coronary Syndrome (ACS) is a clinical syndrome comprising ST Segment Elevation Myocardial Infarction (STEMI), Non-ST Segment Elevation Myocardial Infarction (NSTEMI), and Unstable Angina (UA). ACS is a common and important diagnosis that is often made in the emergency department by front-line physicians and rapid recognition and diagnosis of ACS, risk stratification, and appropriate treatment have been shown to decrease morbidity and mortality [1]. In the context of ACS treatment, dual antiplatelet therapy with ASA and clopidogrel (a P2Y12 receptor inhibitor) reduces rates of harmful cardiac events such as cardiovascular causes of death, myocardial infarction, and stroke [2]. However, with new agents undergoing evaluation in large clinical trials, acute care providers need to know if the new P2Y12 receptor inhibitor antiplatelet agents ticagrelor and prasugrel are clinically superior to the current standard clopidogrel. It has been established that a defined percentage of the population exhibits high platelet activity despite the use of clopidogrel. This phenomenon occurs anywhere from 5% to 44% of patients studied depending on the clopidogrel dose and patient population [3]. It is uncertain what level of platelet activity during ACS
References
[1]
R. R. Arora and F. Rai, “Antiplatelet intervention in acute coronary syndrome,” American Journal of Therapeutics, vol. 16, no. 5, pp. e29–e40, 2009.
[2]
K. A. A. Fox, S. R. Mehta, R. Peters et al., “Benefits and risks of the combination of clopidogrel and aspirin in patients undergoing surgical revascularization for non- ST-elevation acute coronary syndrome: the clopidogrel in unstable angina to prevent recurrent ischemic events (CURE) trial,” Circulation, vol. 110, no. 10, pp. 1202–1208, 2004.
[3]
P. A. Gurbel and U. S. Tantry, “Clopidogrel resistance?” Thrombosis Research, vol. 120, no. 3, pp. 311–321, 2007.
[4]
P. M. Vila, M. U. Zafar, and J. J. Badimon, “Platelet reactivity and nonresponse to dual antiplatelet therapy: a review,” Platelets, vol. 20, no. 8, pp. 531–538, 2009.
[5]
S. D. Wiviott, D. Trenk, A. L. Frelinger 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, vol. 116, no. 25, pp. 2923–2932, 2007.
[6]
P. A. Gurbel, K. P. Bliden, K. Butler et al., “Response to ticagrelor in clopidogrel nonresponders and responders and effect of switching therapies: The RESPOND Study,” Circulation, vol. 121, no. 10, pp. 1188–1199, 2010.
[7]
M. Valgimigli, M. Tebaldi, G. Campo, et al., “Prasugrel versus tirofiban bolus with or without short post-bolus infusion with or without concomitant prasugreladministration in patients with myocardial infarction undergoing coronary stenting: the FABOLUS PRO, (Facilitation through Aggrastat by dropping or shortening Infusion Line in patients with ST-segment elevation myocardial infarction compared to or on top of PRasugrel given at loading dose) trial,” Journal of the American College of Cardiology, vol. 5, no. 3, pp. 268–277, 2012.
[8]
“Clopidogrel,” in UpToDate, D. S. Basow, Ed., UpToDate, Waltham, Mass, USA, 2012.
[9]
D. W. Marion, “Ticagrelor,” in UpToDate, D. S. Basow, Ed., UpToDate, Waltham, Mass, USA, 2012.
[10]
D. W. Marion, “Prasugrel,” in UpToDate, D. S. Basow, Ed., UpToDate, Waltham, Mass, USA, 2012.
[11]
S. D. Wiviott, E. Braunwald, C. H. McCabe et al., “Prasugrel versus clopidogrel in patients with acute coronary syndromes,” The New England Journal of Medicine, vol. 357, no. 20, pp. 2001–2015, 2007.
[12]
M. T. Roe, P. W. Armstrong, K. A. Fox, et al., “Prasugrel versus clopidogrel for acute coronary syndromes without revascularization,” The New England Journal of Medicine, vol. 367, no. 14, pp. 1297–1309, 2012.
[13]
E. M. Antman, M. Cohen, P. J. L. M. Bernink et al., “The TIMI risk score for unstable angina/non-ST elevation MI: a method for prognostication and therapeutic decision making,” Journal of the American Medical Association, vol. 284, no. 7, pp. 835–842, 2000.
[14]
S. D. Wiviott, E. M. Antman, C. M. Gibson 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),” American Heart Journal, vol. 152, no. 4, pp. 627–635, 2006.
[15]
Y. B. Song, J. Y. Hahn, H. C. Gwon, et al., “A high loading dose of clopidogrel reduces myocardial infarct size in patients undergoing primary percutaneous coronary intervention: a magnetic resonance imaging study,” American Heart Journal, vol. 163, no. 3, pp. 500–507, 2012.
[16]
G. Patti, G. Bárczi, D. Orlic, et al., “Outcome comparison of 600- and 300-mg loading doses of clopidogrel in patients undergoing primary percutaneous coronary intervention for ST-segment elevation myocardial infarction: results from the ARMYDA-6 MI, (Antiplatelet therapy for Reduction of MYocardial Damage during Angioplasty-Myocardial Infarction) randomized study,” Journal of the American College of Cardiology, vol. 58, no. 15, pp. 1592–1599, 2011.
[17]
F. Mangiacapra, O. Muller, A. Ntalianis et al., “Comparison of 600 versus 300-mg clopidogrel loading dose in patients with St-segment elevation myocardial infarction undergoing primary coronary angioplasty,” American Journal of Cardiology, vol. 106, no. 9, pp. 1208–1211, 2010.
[18]
J. M. Siller-Matula, K. Huber, G. Christ et al., “Impact of clopidogrel loading dose on clinical outcome in patients undergoing percutaneous coronary intervention: a systematic review and meta-analysis,” Heart, vol. 97, no. 2, pp. 98–105, 2011.
[19]
G. Montalescot, L. Bolognese, D. Dudek et al., “A Comparison of prasugrel at the time of percutaneous Coronary intervention or as pretreatment at the time of diagnosis in patients with non-ST-segment elevation myocardial infarction: design and rationale for the ACCOAST study,” American Heart Journal, vol. 161, no. 4, pp. 650.e1–656.e1, 2011.
[20]
L. Wallentin, R. C. Becker, A. Budaj et al., “Ticagrelor versus clopidogrel in patients with acute coronary syndromes,” The New England Journal of Medicine, vol. 361, no. 11, pp. 1045–1057, 2009.
[21]
G. Biondi-Zoccai, M. Lotrionte, P. Agostoni et al., “Adjusted indirect comparison meta-analysis of prasugrel versus ticagrelor for patients with acute coronary syndromes,” International Journal of Cardiology, vol. 150, no. 3, pp. 325–331, 2011.
[22]
E. M. Antman, D. T. Anbe, P. W. Armstrong et al., “ACC/AHA guidelines for the management of patients with ST-elevation myocardial infarction—executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (writing committee to revise the 1999 guidelines for the management of patients with acute myocardial infarction),” Circulation, vol. 110, no. 5, pp. 588–636, 2004.
[23]
E. M. Antman, M. Hand, P. W. Armstrong, et al., “2007 focused update of the ACC/AHA, 2004 guidelines for the management of patients with ST-elevation myocardial infarction: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines,” Journal of the American College of Cardiology, vol. 51, no. 2, pp. 210–247, 2008.
[24]
F. G. Kushner, M. Hand, S. C. Smith 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),” Journal of the American College of Cardiology, vol. 54, no. 23, pp. 2205–2241, 2009.
[25]
J. L. Anderson, C. D. Adams, E. M. Antman et al., “ACC/AHA 2007 guidelines for the management of patients with unstable angina/non-ST-elevation myocardial infarction. A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (writing committee to revise the 2002 guidelines for the management of patients with unstable angina/non-ST-elevation myocardial infarction),” Journal of the American College of Cardiology, vol. 50, no. 7, pp. e1–e157, 2007.
[26]
R. S. Wright, J. L. Anderson, C. D. Adams et al., “2011 ACCF/AHA focused update of the Guidelines for the Management of Patients with Unstable Angina/Non-ST-Elevation Myocardial Infarction (updating the 2007 guideline): a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines developed in collaboration with the American College of Emergency Physicians, Society for Cardiovascular,” Journal of the American College of Cardiology, vol. 57, no. 19, pp. 1920–1959, 2011.
[27]
H. Jneid, J. L. Anderson, R. S. Wright, 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),” Journal of the American College of Cardiology, vol. 60, no. 7, pp. 645–681, 2012.
[28]
C. W. Hamm, J. P. Bassand, S. Agewall, 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),” European Heart Journal, vol. 32, no. 23, pp. 2999–3054, 2011.
[29]
P. G. Steg, S. K. James, D. Atar, et al., “ESC Guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation The Task Force on the management of ST-segment elevation acute myocardial infarction of the European Society of Cardiology (ESC),” European Heart Journal, vol. 33, no. 20, pp. 2569–2619, 2012.
