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Published in: Cardiovascular Intervention and Therapeutics 4/2017

01-10-2017 | Original Article

Changes in P2Y12 reaction units after switching treatments from prasugrel to clopidogrel in Japanese patients with acute coronary syndrome followed by elective coronary stenting

Authors: Takafumi Ueno, Hiroshi Koiwaya, Ken-ichiro Sasaki, Yoshio Katsuki, Yousuke Katsuda, Yoshinobu Murasato, Junichiro Shimamatsu, Kyoko Umeji, Yoritaka Otsuka, Tomohiro Kawasaki, Yoshisato Shibata, Yoshihiro Fukumoto

Published in: Cardiovascular Intervention and Therapeutics | Issue 4/2017

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Abstract

Patients with ischemic heart disease are administered a dual antiplatelet therapy after percutaneous coronary intervention. This consists of aspirin and thienopyridine, which can be switched from prasugrel to clopidogrel. However, the impact of switching is unknown. This study aimed to determine the efficacy and safety of switching from prasugrel to clopidogrel in Japanese patients. One-hundred and thirty-six patients with acute coronary syndrome scheduled to undergo percutaneous coronary intervention and patients with coronary artery disease requiring elective coronary stenting were enrolled. Patients were randomly assigned into the following groups: prasugrel for 6 weeks at loading/maintenance doses of 20/3.75 mg (Continued Group; n = 68) or prasugrel at 20/3.75 mg for 2 weeks followed by clopidogrel at 75 mg for 4 weeks (Switched Group; n = 68). Aspirin (loading dose/maintenance dose 324/81–100 mg/day) was coadministered in both groups. The primary endpoint was the mean P2Y12 reaction unit (PRU) at week 6 and the secondary endpoint was the PRU in groups subdivided based on the presence of CYP2C19 gene polymorphisms. At week 6, the PRU was significantly lower in the Continued Group relative to the Switched Group (140.7 and 183.0, respectively; P < 0.001), which was also evident after correction with the baseline values (144.1 vs. 176.6, respectively; P = 0.005). Extensive and poor metabolizers in the Switched Group, based on CYP2C19 gene polymorphisms, had significantly higher PRU values than those in the Continued Group. Thus, switching treatments from prasugrel to clopidogrel significantly increased the PRU in patients receiving antiplatelet therapy subsequent to percutaneous coronary intervention.
Clinical Trial Registration UMIN ID, UMIN000015122.
Literature
1.
go back to reference O’Gara PT, Kushner FG, Ascheim DD, Casey DE Jr, Chung MK, de Lemos JA, et al. 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. J Am Coll Cardiol. 2013;61(4):e78–140.CrossRefPubMed O’Gara PT, Kushner FG, Ascheim DD, Casey DE Jr, Chung MK, de Lemos JA, et al. 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. J Am Coll Cardiol. 2013;61(4):e78–140.CrossRefPubMed
2.
go back to reference Levine GN, Bates ER, Blankenship JC, Bailey SR, Bittl JA, Cercek B, et al. 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. J Am Coll Cardiol. 2011;58(24):e44–122.CrossRefPubMed Levine GN, Bates ER, Blankenship JC, Bailey SR, Bittl JA, Cercek B, et al. 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. J Am Coll Cardiol. 2011;58(24):e44–122.CrossRefPubMed
3.
go back to reference Windecker S, Kolh P, Alfonso F, Collet JP, Cremer J, Falk V, et al. ESC/EACTS Guidelines onmyocardial 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. 2014;35:2541–619.CrossRefPubMed Windecker S, Kolh P, Alfonso F, Collet JP, Cremer J, Falk V, et al. ESC/EACTS Guidelines onmyocardial 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. 2014;35:2541–619.CrossRefPubMed
5.
go back to reference Steinhubl SR, Berger PB, Mann JT 3rd, Fry ET, DeLago A, Wilmer C, et al. Early and sustained dual oral antiplatelet therapy following percutaneous coronary intervention. A randomized controlled trial. JAMA. 2002;288(19):2411–20.CrossRefPubMed Steinhubl SR, Berger PB, Mann JT 3rd, Fry ET, DeLago A, Wilmer C, et al. Early and sustained dual oral antiplatelet therapy following percutaneous coronary intervention. A randomized controlled trial. JAMA. 2002;288(19):2411–20.CrossRefPubMed
6.
go back to reference 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(3):153–67.CrossRefPubMed 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(3):153–67.CrossRefPubMed
7.
go back to reference Saito S, Isshiki T, Kimura T, Ogawa H, Yokoi H, Nanto S, 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(7):1684–92.CrossRefPubMed Saito S, Isshiki T, Kimura T, Ogawa H, Yokoi H, Nanto S, 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(7):1684–92.CrossRefPubMed
8.
go back to reference Yamamoto K, Hokimoto S, Chitose T, Morita K, Ono T, Kaikita K, et al. Impact of CYP2C19 gene polymorphism on residual platelet reactivity in patients with coronary heart disease during antiplatelet therapy. J Cardiol. 2011;57(2):194–201.CrossRefPubMed Yamamoto K, Hokimoto S, Chitose T, Morita K, Ono T, Kaikita K, et al. Impact of CYP2C19 gene polymorphism on residual platelet reactivity in patients with coronary heart disease during antiplatelet therapy. J Cardiol. 2011;57(2):194–201.CrossRefPubMed
9.
go back to reference 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(20):2001–15.CrossRefPubMed 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(20):2001–15.CrossRefPubMed
10.
go back to reference Sorich MJ, Vitry A, Ward MB, Horowitz JD, McKinnon RA. Prasugrel vs. clopidogrel for cytochrome P450 2C19-genotyped subgroups: integration of the TRITON-TIMI 38 trial data. J Thromb Haemost. 2010;8(8):1678–84.CrossRefPubMed Sorich MJ, Vitry A, Ward MB, Horowitz JD, McKinnon RA. Prasugrel vs. clopidogrel for cytochrome P450 2C19-genotyped subgroups: integration of the TRITON-TIMI 38 trial data. J Thromb Haemost. 2010;8(8):1678–84.CrossRefPubMed
11.
go back to reference Isshiki T, Kimura T, Ogawa H, Yokoi H, Nanto S, Takayama M, et al. Prasugrel, a third-generation P2Y12 receptor antagonist, in patients with coronary artery disease undergoing elective percutaneous coronary intervention. Circ J. 2014;78(12):2926–34.CrossRefPubMed Isshiki T, Kimura T, Ogawa H, Yokoi H, Nanto S, Takayama M, et al. Prasugrel, a third-generation P2Y12 receptor antagonist, in patients with coronary artery disease undergoing elective percutaneous coronary intervention. Circ J. 2014;78(12):2926–34.CrossRefPubMed
12.
go back to reference Angiolillo DJ, Saucedo JF, DeRaad R, Frelinger AL, Gurbel PA, Costigan TM, et al. Increased platelet inhibition after switching from maintenance clopidogrel to prasugrel in patients with acute coronary syndromes: results of the SWAP (SWitching Anti Platelet) study. J Am Coll Cardiol. 2010;56(13):1017–23.CrossRefPubMed Angiolillo DJ, Saucedo JF, DeRaad R, Frelinger AL, Gurbel PA, Costigan TM, et al. Increased platelet inhibition after switching from maintenance clopidogrel to prasugrel in patients with acute coronary syndromes: results of the SWAP (SWitching Anti Platelet) study. J Am Coll Cardiol. 2010;56(13):1017–23.CrossRefPubMed
13.
go back to reference The ethical guidelines for clinical studies (the Ministry of Health, Labour and Welfare, 30 July 2003, 31 July 2008 revised). The ethical guidelines for clinical studies (the Ministry of Health, Labour and Welfare, 30 July 2003, 31 July 2008 revised).
14.
go back to reference Ethical Guidelines for Human Genome/Gene Analysis Research (Ministry of Education, Culture, Sports, Science and Technology, Ministry of Health, Labour and Welfare and Ministry of Economy, Trade and Industry, 29 Mar 2001, 8 Feb 2013 revised). Ethical Guidelines for Human Genome/Gene Analysis Research (Ministry of Education, Culture, Sports, Science and Technology, Ministry of Health, Labour and Welfare and Ministry of Economy, Trade and Industry, 29 Mar 2001, 8 Feb 2013 revised).
15.
go back to reference Stone GW, Witzenbichler B, Weisz G, Rinaldi MJ, Neumann FJ, Metzger DC, et al. Platelet reactivity and clinical outcomes after coronary artery implantation of drug-eluting stents (ADAPT-DES): a prospective multicentre registry study. Lancet. 2013;382(9892):614–23.CrossRefPubMed Stone GW, Witzenbichler B, Weisz G, Rinaldi MJ, Neumann FJ, Metzger DC, et al. Platelet reactivity and clinical outcomes after coronary artery implantation of drug-eluting stents (ADAPT-DES): a prospective multicentre registry study. Lancet. 2013;382(9892):614–23.CrossRefPubMed
16.
go back to reference Wiviott SD, Antman EM, Gibson CM, Montalescot G, Riesmeyer J, Weerakkody G, 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). Am Heart J. 2006;152(4):627–35.CrossRefPubMed Wiviott SD, Antman EM, Gibson CM, Montalescot G, Riesmeyer J, Weerakkody G, 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). Am Heart J. 2006;152(4):627–35.CrossRefPubMed
17.
go back to reference Mehran R, Rao SV, Bhatt DL, Gibson CM, Caixeta A, Eikelboom J, et al. Standardized bleeding definitions for cardiovascular clinical trials a consensus report from the bleeding academic research consortium. Circulation. 2011;123(23):2736–47.CrossRefPubMed Mehran R, Rao SV, Bhatt DL, Gibson CM, Caixeta A, Eikelboom J, et al. Standardized bleeding definitions for cardiovascular clinical trials a consensus report from the bleeding academic research consortium. Circulation. 2011;123(23):2736–47.CrossRefPubMed
18.
go back to reference Levine GN, Jeong YH, Goto S, Anderson JL, Huo Y, Mega JL, et al. Expert consensus document: World Heart Federation expert consensus statement on antiplatelet therapy in East Asian patients with ACS or undergoing PCI. Nat Rev Cardiol. 2014;11(10):597–606.CrossRefPubMed Levine GN, Jeong YH, Goto S, Anderson JL, Huo Y, Mega JL, et al. Expert consensus document: World Heart Federation expert consensus statement on antiplatelet therapy in East Asian patients with ACS or undergoing PCI. Nat Rev Cardiol. 2014;11(10):597–606.CrossRefPubMed
19.
go back to reference 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(24):2261–73.CrossRefPubMed 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(24):2261–73.CrossRefPubMed
20.
go back to reference Brar SS, ten Berg J, Marcucci R, Marcucci R, Price MJ, Valgimigli M, et al. Impact of platelet reactivity on clinical outcomes after percutaneous coronary intervention: a collaborative meta-analysis of individual participant data. J Am Coll Cardiol. 2011;58(19):1945–54.CrossRefPubMed Brar SS, ten Berg J, Marcucci R, Marcucci R, Price MJ, Valgimigli M, et al. Impact of platelet reactivity on clinical outcomes after percutaneous coronary intervention: a collaborative meta-analysis of individual participant data. J Am Coll Cardiol. 2011;58(19):1945–54.CrossRefPubMed
21.
go back to reference Kimura T, Isshiki T, Ogawa H, Yokoi H, Yamaguchi T, Ikeda Y. Randomized, double-blind, dose-finding, phase ii study of prasugrel in Japanese patients undergoing elective percutaneous coronary intervention. J Atheroscler Thromb. 2015;22(6):557–69.CrossRefPubMed Kimura T, Isshiki T, Ogawa H, Yokoi H, Yamaguchi T, Ikeda Y. Randomized, double-blind, dose-finding, phase ii study of prasugrel in Japanese patients undergoing elective percutaneous coronary intervention. J Atheroscler Thromb. 2015;22(6):557–69.CrossRefPubMed
22.
go back to reference Mega JL, Close SL, Wiviott SD, Shen L, Hockett RD, Brandt JT, et al. Cytochrome p-450 polymorphisms and response to clopidogrel. N Engl J Med. 2009;360(4):354–62.CrossRefPubMed Mega JL, Close SL, Wiviott SD, Shen L, Hockett RD, Brandt JT, et al. Cytochrome p-450 polymorphisms and response to clopidogrel. N Engl J Med. 2009;360(4):354–62.CrossRefPubMed
23.
go back to reference Mega JL, Close SL, Wiviott SD, Shen L, Hockett RD, Brandt JT, et al. Cytochrome P450 genetic polymorphisms and the response to prasugrel: relationship to pharmacokinetic, pharmacodynamic, and clinical outcomes. Circulation. 2009;119(19):2553–60.CrossRefPubMed Mega JL, Close SL, Wiviott SD, Shen L, Hockett RD, Brandt JT, et al. Cytochrome P450 genetic polymorphisms and the response to prasugrel: relationship to pharmacokinetic, pharmacodynamic, and clinical outcomes. Circulation. 2009;119(19):2553–60.CrossRefPubMed
Metadata
Title
Changes in P2Y12 reaction units after switching treatments from prasugrel to clopidogrel in Japanese patients with acute coronary syndrome followed by elective coronary stenting
Authors
Takafumi Ueno
Hiroshi Koiwaya
Ken-ichiro Sasaki
Yoshio Katsuki
Yousuke Katsuda
Yoshinobu Murasato
Junichiro Shimamatsu
Kyoko Umeji
Yoritaka Otsuka
Tomohiro Kawasaki
Yoshisato Shibata
Yoshihiro Fukumoto
Publication date
01-10-2017
Publisher
Springer Japan
Published in
Cardiovascular Intervention and Therapeutics / Issue 4/2017
Print ISSN: 1868-4300
Electronic ISSN: 1868-4297
DOI
https://doi.org/10.1007/s12928-016-0417-x

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