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Impact of dual antiplatelet therapy with adjusted-dose prasugrel on mid-term vascular response in patients undergoing elective percutaneous coronary intervention with everolimus-eluting stents

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Abstract

The impact of dual antiplatelet therapy (DAPT) with adjusted-dose (3.75 mg/day) prasugrel for Japanese patients has not been fully investigated in terms of local arterial healing following the elective percutaneous coronary intervention (PCI). The ROUTE-01 elective study was a prospective, 12-center and single-arm registry that enrolled 123 patients who underwent elective PCI with everolimus-eluting stents (EESs) under DAPT with a combination of adjusted-dose prasugrel and aspirin. Serial optical coherence tomography (OCT) was performed at the index PCI and 9-month follow-up to assess the relationship between in-stent thorombus (IST) and residual platelet reactivity measuring platelet reactivity unit (PRU). The patients were classified as extensive, intermediate, and poor metabolizers by cytochrome P450 2C19 (CYP2C19) loss-of-function polymorphisms. The prevalence of IST was 9.0% by 9-month OCT, with no difference amongst the three groups (p = 0.886). The incidences of malapposed and uncovered struts were not different among the groups. PRU was not statistically different among the groups. In multivariate logistic regression analysis, the independent predictor for IST on 9-month OCT was irregular protrusion (odds ratio = 8.952, p = 0.037) on post-PCI OCT, not CYP2C19 loss-of-function polymorphisms. An adequate anti-thrombotic effect with an acceptable incidence of IST was observed irrespective of CYP2C19 loss-of-function polymorphisms. Our data suggests that adjusted-dose prasugrel and aspirin is a feasible treatment option in Japanese patients treated with EESs in elective PCI.

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References

  1. Valgimigli M, Bueno H, Byrne RA, Collet JP, Costa F, Jeppsson A, Jüni P, Kastrati A, Kolh P, Mauri L, Montalescot G, Neumann FJ, Petricevic M, Roffi M, Steg PG, Windecker S, Zamorano JL, Levine GN, ESC Scientific Document Group (2018) 2017 ESC focused update on dual antiplatelet therapy in coronary artery disease developed in collaboration with EACTS. Eur J Cardiothorac Surg 53:34–78

    Article  PubMed  Google Scholar 

  2. Levine GN, Bates ER, Bittl JA, Brindis RG, Fihn SD, Fleisher LA, Granger CB, Lange RA, Mack MJ, Mauri L, Mehran R, Mukherjee D, Newby LK, O'Gara PT, Sabatine MS, Smith PK, Smith SC Jr, Halperin JL, Levine GN, Al-Khatib SM, Birtcher KK, Bozkurt B, Brindis RG, Cigarroa JE, Curtis LH, Fleisher LA, Gentile F, Gidding S, Hlatky MA, Ikonomidis JS, Joglar JA, Pressler SJ, Wijeysundera DN (2016) 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 68:1082–1115

    Article  Google Scholar 

  3. Collet JP, Hulot JS, Pena A, Villard E, Esteve JB, Silvain J, Payot L, Brugier D, Cayla G, Beygui F, Bensimon G, Funck-Brentano C, Montalescot G (2009) Cytochrome P450 2C19 polymorphism in young patients treated with clopidogrel after myocardial infarction: a cohort study. Lancet 373:309–317

    Article  CAS  PubMed  Google Scholar 

  4. Mega JL, Close SL, Wiviott SD, Shen L, Hockett RD, Brandt JT, Walker JR, Antman EM, Macias W, Braunwald E, Sabatine MS (2009) Cytochrome p-450 polymorphisms and response to clopidogrel. N Engl J Med 360:354–362

    Article  CAS  PubMed  Google Scholar 

  5. Rehmel JL, Eckstein JA, Farid NA, Heim JB, Kasper SC, Kurihara A, Wrighton SA, Ring BJ (2006) Interactions of two major metabolites of prasugrel, a thienopyridine antiplatelet agent, with the cytochromes P450. Drug Metab Dispos 34:600–607

    Article  CAS  PubMed  Google Scholar 

  6. Farid NA, Payne CD, Small DS, Winters KJ, Ernest CS 2nd, Brandt JT, Darstein C, Jakubowski JA, Salazar DE (2007) Cytochrome P450 3A inhibition by ketoconazole affects prasugrel and clopidogrel pharmacokinetics and pharmacodynamics differently. Clin Pharmacol Ther 81:735–741

    Article  CAS  PubMed  Google Scholar 

  7. Isshiki T, Kimura T, Ogawa H, Yokoi H, Nanto S, Takayama M, Kitagawa K, Nishikawa M, Miyazaki S, Ikeda Y, Nakamura M, Saito S, PRASFIT-ElectiveInvestigators (2014) Prasugrel, a third-generation P2Y12 receptor antagonist, in patients with coronary artery disease undergoing elective percutaneous coronary intervention. Circ J 78:2926–2934

    Article  CAS  PubMed  Google Scholar 

  8. Tearney GJ, Regar E, Akasaka T, Adriaenssens T, Barlis P, Bezerra HG, Bouma B, Bruining N, Cho JM, Chowdhary S, Costa MA, de Silva R, Dijkstra J, Di Mario C, Dudek D, Falk E, Feldman MD, Fitzgerald P, Garcia-Garcia HM, Gonzalo N, Granada JF, Guagliumi G, Holm NR, Honda Y, Ikeno F, Kawasaki M, Kochman J, Koltowski L, Kubo T, Kume T, Kyono H, Lam CC, Lamouche G, Lee DP, Leon MB, Maehara A, Manfrini O, Mintz GS, Mizuno K, Morel MA, Nadkarni S, Okura H, Otake H, Pietrasik A, Prati F, Räber L, Radu MD, Rieber J, Riga M, Rollins A, Rosenberg M, Sirbu V, Serruys PW, Shimada K, Shinke T, Shite J, Siegel E, Sonoda S, Suter M, Takarada S, Tanaka A, Terashima M, Thim T, Uemura S, Ughi GJ, van Beusekom HM, van der Steen AF, van Es GA, van Soest G, Virmani R, Waxman S, Weissman J, Weisz, International Working Group for Intravascular Optical Coherence Tomography (IWG-IVOCT) (2012) Consensus standards for acquisition, measurement, and reporting of intravascular optical coherence tomography studies: a report from the International Working Group for Intravascular Optical Coherence Tomography Standardization and Validation. J Am Coll Cardiol 59:1058–1072

    Article  PubMed  Google Scholar 

  9. Nishio R, Shinke T, Otake H, Sawada T, Haraguchi Y, Shinohara M, Toh R, Ishida T, Nakagawa M, Nagoshi R, Kozuki A, Inoue T, Hariki H, Osue T, Taniguchi Y, Iwasaki M, Hiranuma N, Konishi A, Kinutani H, Shite J, Hirata K (2012) Effect of cytochrome P450 2C19 polymorphism on target lesion outcome after drug-eluting stent implantation in Japanese patients receiving clopidogrel. Circ J 76:2348–2355

    Article  CAS  PubMed  Google Scholar 

  10. Konishi A, Shinke T, Otake H, Nishio R, Sawada T, Takaya T, Nakagawa M, Osue T, Taniguchi Y, Iwasaki M, Kinutani H, Masaru K, Takahashi H, Terashita D, Shite J, Hirata K (2015) Impact of cytochrome P450 2C19 loss-of-function polymorphism on intra-stent thrombi and lesion outcome after everolimus-eluting stent implantation compared to that after first-generation drug-eluting stent implantation. Int J Cardiol 179:476–483

    Article  PubMed  Google Scholar 

  11. Patil SB, Jackman LE, Francis SE, Judge HM, Nylander S, Storey RF (2010) Ticagrelor effectively and reversibly blocks murine platelet P2Y12-mediated thrombosis and demonstrates a requirement for sustained P2Y12 inhibition to prevent subsequent neointima. Arterioscler Thromb Vasc Biol 30:2385–2391

    Article  CAS  PubMed  Google Scholar 

  12. Soeda T, Uemura S, Park SJ, Jang Y, Lee S, Cho JM, Kim SJ, Vergallo R, Minami Y, Ong DS, Gao L, Lee H, Zhang S, Yu B, Saito Y, Jang IK (2015) Incidence and clinical significance of poststent optical coherence tomography findings: one-year follow-up study from a multicenter registry. Circulation 132:1020–1029

    Article  PubMed  Google Scholar 

  13. Gonzalo N, Serruys PW, Okamura T, Shen ZJ, Onuma Y, Garcia-Garcia HM, Sarno G, Schultz C, van Geuns RJ, Ligthart J, Regar E (2009) Optical coherence tomography assessment of the acute effects of stent implantation on the vessel wall: a systematic quantitative approach. Heart 95:1913–1919

    Article  CAS  PubMed  Google Scholar 

  14. Inoue T, Shite J, Yoon J, Shinke T, Otake H, Sawada T, Kawamori H, Katoh H, Miyoshi N, Yoshino N, Kozuki A, Hariki H, Hirata K (2011) Optical coherence evaluation of everolimus-eluting stents 8 months after implantation. Heart 97:1379–1384

    Article  CAS  PubMed  Google Scholar 

  15. Nakamura M, Isshiki T, Kimura T, Ogawa H, Yokoi H, Nanto S, Takayama M, Kitagawa K, Ikeda Y, Saito S (2015) Optimal cutoff value of P2Y12 reaction units to prevent major adverse cardiovascular events in the acute periprocedural period: post-hoc analysis of the randomized PRASFIT-ACS study. Int J Cardiol 182:541–548

    Article  PubMed  Google Scholar 

  16. Cutlip DE, Windecker S, Mehran R, Boam A, Cohen DJ, van Es GA, Steg PG, Morel MA, Mauri L, Vranckx P, McFadden E, Lansky A, Hamon M, Krucoff MW, Serruys PW, Academic Research Consortium (2007) Clinical end points in coronary stent trials: a case for standardized definitions. Circulation 115:2344–2351

    Article  Google Scholar 

  17. Saito S, Isshiki T, Kimura T, Ogawa H, Yokoi H, Nanto S, Takayama M, Kitagawa K, Nishikawa M, Miyazaki S, Nakamura M (2014) Efficacy and safety of adjusted-dose prasugrel compared with clopidogrel in Japanese patients with acute coronary syndrome: the PRASFIT-ACS study. Circ J 78:1684–1692

    Article  CAS  PubMed  Google Scholar 

  18. Mehran R, Rao SV, Bhatt DL, Gibson CM, Caixeta A, Eikelboom J, Kaul S, Wiviott SD, Menon V, Nikolsky E, Serebruany V, Valgimigli M, Vranckx P, Taggart D, Sabik JF, Cutlip DE, Krucoff MW, Ohman EM, Steg PG, White H (2011) Standardized bleeding definitions for cardiovascular clinical trials: a consensus report from the Bleeding Academic Research Consortium. Circulation 123:2736–2747

    Article  PubMed  Google Scholar 

  19. Sugiyama T, Kimura S, Akiyama D, Hishikari K, Kawaguchi N, Kamiishi T, Hikita H, Takahashi A, Isobe M (2014) Quantitative assessment of tissue prolapse on optical coherence tomography and its relation to underlying plaque morphologies and clinical outcome in patients with elective stent implantation. Int J Cardiol 176:182–190

    Article  PubMed  Google Scholar 

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Acknowledgments

We acknowledge the support of the institutions that took part in the current study and appreciate the contributions of all the investigators and staff involved in this study.

Funding

The current study was sponsored by Daiichi Sankyo Co., Ltd. (Tokyo, Japan).

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Authors and Affiliations

  1. Division of Cardiovascular Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine, 7-5-2, Kusunoki-cho, Chuo-ku, Kobe, 6500017, Japan

    Takayoshi Toba, Toshiro Shinke, Hiromasa Otake, Yoichiro Sugizaki, Ryo Takeshige, Hiroyuki Onishi, Akira Nagasawa, Yoshiro Tsukiyama, Kenichi Yanaka, Yuichiro Nagano, Hiroyuki Yamamoto, Hiroyuki Kawamori & Ken-ichi Hirata

  2. Showa University School of Medicine, Tokyo, Japan

    Toshiro Shinke

  3. Akashi Medical Center, Akashi, Japan

    Akira Matsuura

  4. Kansai Rosai Hospital, Amagasaki, Japan

    Takayuki Ishihara

  5. Yodogawa Christian Hospital, Osaka, Japan

    Daisuke Matsumoto

  6. Japanese Red Cross Kobe Hospital, Kobe, Japan

    Nobuaki Igarashi

  7. Hyogo Prefectural Awaji Medical Center, Sumoto, Japan

    Takatoshi Hayashi

  8. Hyogo Brain and Heart Center, Himeji, Japan

    Yoshinori Yasaka

  9. Kakogawa Central City Hospital, Kakogawa, Japan

    Makoto Kadotani

  10. Ako City Hospital, Ako, Japan

    Takashi Fujii

  11. Saiseikai Nakatsu Hospital, Osaka, Japan

    Junya Shite

  12. Shiga General Hospital, Moriyama, Japan

    Masaharu Okada

  13. Nagoya Kyoritsu Hospital, Nagoya, Japan

    Takashi Sakakibara

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  1. Takayoshi Toba
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Corresponding author

Correspondence to Toshiro Shinke.

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Conflict of interest

The current study was sponsored by Daiichi Sankyo Co., Ltd. (Tokyo, Japan). The authors declare the following interests: Toshiro Shinke, Hiromasa Otake and Junya Shite are medical advisors for Abbott Vascular Japan Co., Ltd. (Nagoya, Japan). Other authors have nothing to disclose regarding the current study.

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Toba, T., Shinke, T., Otake, H. et al. Impact of dual antiplatelet therapy with adjusted-dose prasugrel on mid-term vascular response in patients undergoing elective percutaneous coronary intervention with everolimus-eluting stents. Heart Vessels 34, 936–947 (2019). https://doi.org/10.1007/s00380-018-1322-2

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  • DOI: https://doi.org/10.1007/s00380-018-1322-2

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