Int J Angiol 2023; 32(01): 056-065
DOI: 10.1055/s-0042-1746417
Original Article

Infarct Size and Long-Term Clinical Outcomes of Prasugrel versus Clopidogrel in Patients with Acute Coronary Syndrome Undergoing Coronary Artery Stenting: A Prospective Randomized Study

Takayuki Yabe
1   Department of Cardiovascular Medicine, Toho University Faculty of Medicine, Tokyo, Japan
,
Ryota Noike
1   Department of Cardiovascular Medicine, Toho University Faculty of Medicine, Tokyo, Japan
,
Ryo Okubo
1   Department of Cardiovascular Medicine, Toho University Faculty of Medicine, Tokyo, Japan
,
Hideo Amano
1   Department of Cardiovascular Medicine, Toho University Faculty of Medicine, Tokyo, Japan
,
Takanori Ikeda
1   Department of Cardiovascular Medicine, Toho University Faculty of Medicine, Tokyo, Japan
› Author Affiliations

Abstract

The antiplatelet drug prasugrel inhibits platelet aggregation early after oral administration. This study examined whether prasugrel is effective in inhibiting infarct size and can reduce the incidence of major adverse cardiovascular events (MACE) in patients with acute coronary syndrome (ACS). This study was a single-center, prospective, randomized pilot study. Among 80 ACS patients treated at our institution between August 2014 and September 2015, 76 ACS patients who underwent stenting and achieved thrombolysis in myocardial infarction flow grade 3 were assigned to receive aspirin plus prasugrel (prasugrel group; n = 37) or aspirin plus clopidogrel (clopidogrel group; n = 39). The primary endpoint was survival free of MACE. The secondary endpoint was the evaluation of infarct size defined as the area under the curve (AUC) of troponin I, calculated using the linear trapezoidal method. During follow-up (mean, 1262.4 ± 599.6 days), 14 patients showed MACE. No significant differences in CYP2C19 genotype were seen between groups. AUC of troponin I up to 72 hours after intervention tended to be smaller in the prasugrel group (1,927.1 ± 2,189.3 ng/mL) than in the clopidogrel group (3,186.0 ± 3,760.1 ng/mL, p = 0.08). Cumulative incidence of MACE was significantly higher in the clopidogrel group (log-rank test; p = 0.02). Compared with clopidogrel, prasugrel was associated with reduced infarct size and lower frequency of long-term outcomes among ACS patients undergoing stenting.



Publication History

Article published online:
19 July 2022

© 2022. International College of Angiology. This article is published by Thieme.

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  • References

  • 1 Amsterdam EA, Wenger NK, Brindis RG. et al. 2014 AHA/ACC Guideline for the Management of Patients with Non-ST-Elevation Acute Coronary Syndromes: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol 2014; 64 (24) e139-e228
  • 2 Roffi M, Patrono C, Collet JP. et al; ESC Scientific Document Group. 2015 ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation: Task Force for the Management of Acute Coronary Syndromes in Patients Presenting without Persistent ST-Segment Elevation of the European Society of Cardiology (ESC). Eur Heart J 2016; 37 (03) 267-315
  • 3 Levine GN, Bates ER, Bittl JA. 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. J Am Coll Cardiol 2016; 68 (10) 1082-1115
  • 4 Cuisset T, Loosveld M, Morange PE. et al. CYP2C19*2 and *17 alleles have a significant impact on platelet response and bleeding risk in patients treated with prasugrel after acute coronary syndrome. JACC Cardiovasc Interv 2012; 5 (12) 1280-1287
  • 5 Frere C, Cuisset T, Morange PE. et al. Effect of cytochrome p450 polymorphisms on platelet reactivity after treatment with clopidogrel in acute coronary syndrome. Am J Cardiol 2008; 101 (08) 1088-1093
  • 6 Hulot JS, Bura A, Villard E. et al. Cytochrome P450 2C19 loss-of-function polymorphism is a major determinant of clopidogrel responsiveness in healthy subjects. Blood 2006; 108 (07) 2244-2247
  • 7 Nagashima Z, Tsukahara K, Morita S. et al. Platelet reactivity in the early and late phases of acute coronary syndromes according to cytochrome P450 2C19 phenotypes. J Cardiol 2013; 62 (03) 158-164
  • 8 Paré G, Mehta SR, Yusuf S. et al. Effects of CYP2C19 genotype on outcomes of clopidogrel treatment. N Engl J Med 2010; 363 (18) 1704-1714
  • 9 Saito S, Isshiki T, Kimura T. et al. Efficacy and safety of adjusted-dose prasugrel compared with clopidogrel in Japanese patients with acute coronary syndrome: the PRASFIT-ACS study. Circ J 2014; 78 (07) 1684-1692
  • 10 Isshiki T, Kimura T, Ogawa H. et al; PRASFIT-Elective Investigators. Prasugrel, a third-generation P2Y12 receptor antagonist, in patients with coronary artery disease undergoing elective percutaneous coronary intervention. Circ J 2014; 78 (12) 2926-2934
  • 11 Katus HA, Remppis A, Neumann FJ. et al. Diagnostic efficiency of troponin T measurements in acute myocardial infarction. Circulation 1991; 83 (03) 902-912
  • 12 Lindahl B, Diderholm E, Lagerqvist B, Venge P, Wallentin L. FRISC II(Fast Revascularization during InStability in CAD) Investigators. Mechanisms behind the prognostic value of troponin T in unstable coronary artery disease: a FRISC II substudy. J Am Coll Cardiol 2001; 38 (04) 979-986
  • 13 Chapman AR, Lee KK, McAllister DA. et al. Association of high-sensitivity cardiac troponin I concentration with cardiac outcomes in patients with suspected acute coronary syndrome. JAMA 2017; 318 (19) 1913-1924
  • 14 Campbell AR, Rodriguez AJ, Larson DM. et al. Resource utilization and outcome among patients with selective versus nonselective troponin testing. Am Heart J 2018; 199: 68-74
  • 15 Antman EM, Tanasijevic MJ, Thompson B. et al. Cardiac-specific troponin I levels to predict the risk of mortality in patients with acute coronary syndromes. N Engl J Med 1996; 335 (18) 1342-1349
  • 16 Licka M, Zimmermann R, Zehelein J, Dengler TJ, Katus HA, Kübler W. Troponin T concentrations 72 hours after myocardial infarction as a serological estimate of infarct size. Heart 2002; 87 (06) 520-524
  • 17 Thygesen K, Alpert JS, Jaffe AS. et al; Joint ESC/ACCF/AHA/WHF Task Force for the Universal Definition of Myocardial Infarction. Third universal definition of myocardial infarction. Circulation 2012; 126 (16) 2020-2035
  • 18 Ishii H, Ichimiya S, Kanashiro M. et al. Impact of a single intravenous administration of nicorandil before reperfusion in patients with ST-segment-elevation myocardial infarction. Circulation 2005; 112 (09) 1284-1288
  • 19 Segev A, Strauss BH, Witztum JL, Lau HK, Tsimikas S. Relationship of a comprehensive panel of plasma oxidized low-density lipoprotein markers to angiographic restenosis in patients undergoing percutaneous coronary intervention for stable angina. Am Heart J 2005; 150 (05) 1007-1014
  • 20 Martis S, Peter I, Hulot JS, Kornreich R, Desnick RJ, Scott SA. Multi-ethnic distribution of clinically relevant CYP2C genotypes and haplotypes. Pharmacogenomics J 2013; 13 (04) 369-377
  • 21 Cutlip DE, Windecker S, Mehran R. et al; Academic Research Consortium. Clinical end points in coronary stent trials: a case for standardized definitions. Circulation 2007; 115 (17) 2344-2351
  • 22 Vollmer RT, Christenson RH, Reimer K, Ohman EM. Temporal creatine kinase curves in acute myocardial infarction. Implications of a good empiric fit with the log-normal function. Am J Clin Pathol 1993; 100 (03) 293-298
  • 23 Ogawa H, Isshiki T, Kimura T. et al. Effects of CYP2C19 allelic variants on inhibition of platelet aggregation and major adverse cardiovascular events in Japanese patients with acute coronary syndrome: the PRASFIT-ACS study. J Cardiol 2016; 68 (01) 29-36
  • 24 Jurima M, Inaba T, Kadar D, Kalow W. Genetic polymorphism of mephenytoin p(4′)-hydroxylation: difference between Orientals and Caucasians. Br J Clin Pharmacol 1985; 19 (04) 483-487
  • 25 Nakamura K, Goto F, Ray WA. et al. Interethnic differences in genetic polymorphism of debrisoquin and mephenytoin hydroxylation between Japanese and Caucasian populations. Clin Pharmacol Ther 1985; 38 (04) 402-408
  • 26 Furuta T, Shirai N, Sugimoto M, Nakamura A, Hishida A, Ishizaki T. Influence of CYP2C19 pharmacogenetic polymorphism on proton pump inhibitor-based therapies. Drug Metab Pharmacokinet 2005; 20 (03) 153-167
  • 27 Umemura K, Iwaki T. The pharmacokinetics and pharmacodynamics of prasugrel and clopidogrel in healthy Japanese volunteers. Clin Pharmacol Drug Dev 2016; 5 (06) 480-487
  • 28 Kitano D, Takayama T, Fukamachi D. et al. Impact of low-dose prasugrel on platelet reactivity and cardiac dysfunction in acute coronary syndrome patients requiring primary drug-eluting stent implantation: a randomized comparative study. Catheter Cardiovasc Interv 2020; 95 (01) E8-E16
  • 29 Tsukahara K, Kimura K, Morita S. et al. Impact of high-responsiveness to dual antiplatelet therapy on bleeding complications in patients receiving drug-eluting stents. Circ J 2010; 74 (04) 679-685
  • 30 Parodi G, Marcucci R, Valenti R. et al. High residual platelet reactivity after clopidogrel loading and long-term cardiovascular events among patients with acute coronary syndromes undergoing PCI. JAMA 2011; 306 (11) 1215-1223
  • 31 Byrne RA, Ndrepepa G, Braun S. et al. Peak cardiac troponin-T level, scintigraphic myocardial infarct size and one-year prognosis in patients undergoing primary percutaneous coronary intervention for acute myocardial infarction. Am J Cardiol 2010; 106 (09) 1212-1217
  • 32 Tzivoni D, Koukoui D, Guetta V, Novack L, Cowing G. CASTEMI Study Investigators. Comparison of Troponin T to creatine kinase and to radionuclide cardiac imaging infarct size in patients with ST-elevation myocardial infarction undergoing primary angioplasty. Am J Cardiol 2008; 101 (06) 753-757
  • 33 Ziegler-Heitbrock L, Ancuta P, Crowe S. et al. Nomenclature of monocytes and dendritic cells in blood. Blood 2010; 116 (16) e74-e80
  • 34 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 (03) 329-334