Skip to main content
SpringerLink
Log in

Cilostazol-based triple versus potent P2Y12 inhibitor-based dual antiplatelet therapy in patients with acute myocardial infarction undergoing percutaneous coronary intervention

  • Original Article
  • Published:
Heart and Vessels Aims and scope Submit manuscript

Abstract

Although potent P2Y12 inhibitor-based dual antiplatelet therapy (DAPT) has replaced clopidogrel-based therapy as the standard treatment in patients with acute myocardial infarction (AMI), there is a concern about the risk of bleeding in East Asian patients. We compared the efficacy and safety of cilostazol-based triple antiplatelet therapy (TAT) with potent P2Y12 inhibitor-based DAPT in Korean patients. A total of 4152 AMI patients who underwent percutaneous coronary intervention (PCI) in the Korea Acute Myocardial Infarction Registry were analyzed retrospectively. Patients were divided into two groups: the TAT group (aspirin + clopidogrel + cilostazol, n = 3161) and the potent DAPT group (aspirin + potent P2Y12 inhibitors [ticagrelor or prasugrel], n = 991). Major clinical outcomes at 30 days and 2 years were compared between the two groups using propensity score matching (PSM) analysis. After PSM (869 pairs), there were no significant differences between the two groups in the incidence of total death, cardiac death, myocardial infarction (MI), target vessel revascularization, stent thrombosis, and stroke at 30 days and 2 years. However, the Thrombolysis in Myocardial Infarction (TIMI) major or minor bleeding rates were significantly lower in the TAT group compared with the potent DAPT group at 2 years (6.4% vs. 3.6%, p = 0.006). In Korean AMI patients undergoing PCI, TAT with cilostazol was associated with lower bleeding than the potent P2Y12 inhibitor-based DAPT without increased ischemic risk. These results could provide a rationale for the use of TAT in East Asian AMI patients.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Levine GN, Jeong YH, Goto S, Anderson JL, Huo Y, Mega JL, Taubert K, Smith SC Jr (2014) Expert consensus document: World Heart Federation expert consensus statement on antiplatelet therapy in East Asian patients with ACS or undergoing PCI. Nat Rev Cardiol 11:597–606

    Article  Google Scholar 

  2. Mak KH, Bhatt DL, Shao M, Hankey GJ, Easton JD, Fox KA, Topol EJ (2009) Ethnic variation in adverse cardiovascular outcomes and bleeding complications in the clopidogrel for high atherothrombotic risk and ischemic stabilization, management, and avoidance (CHARISMA) study. Am Heart J 157:658–665

    Article  CAS  Google Scholar 

  3. Shen AY, Yao JF, Brar SS, Jorgensen MB, Chen W (2007) Racial/ethnic differences in the risk of intracranial hemorrhage among patients with atrial fibrillation. J Am Coll Cardiol 50:309–315

    Article  Google Scholar 

  4. Chen KY, Rha SW, Li YJ, Poddar KL, Jin Z, Minami Y, Wang L, Kim EJ, Park CG, Seo HS, Oh DJ, Jeong MH, Ahn YK, Hong TJ, Kim YJ, Hur SH, Seong IW, Chae JK, Cho MC, Bae JH, Choi DH, Jang YS, Chae IH, Kim CJ, Yoon JH, Chung WS, Seung KB, Park SJ (2009) Triple versus dual antiplatelet therapy in patients with acute ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention. Circulation 119:3207–3214

    Article  CAS  Google Scholar 

  5. Lee S-W, Park S-W, Kim Y-H, Yun S-C, Park D-W, Lee CW, Hong M-K, Kim H-S, Ko J-K, Park J-H (2007) Comparison of triple versus dual antiplatelet therapy after drug-eluting stent implantation (from the DECLARE–Long Trial). Am J Cardiol 100:1103–1108

    Article  CAS  Google Scholar 

  6. Lee S-W, Park S-W, Kim Y-H, Yun S-C, Park D-W, Lee CW, Hong M-K, Kim H-S, Ko J-K, Park J-H (2008) Drug-eluting stenting followed by cilostazol treatment reduces late restenosis in patients with diabetes mellitus: the DECLARE-DIABETES Trial (a randomized comparison of triple antiplatelet therapy with dual antiplatelet therapy after drug-eluting stent implantation in diabetic patients). J Am Coll Cardiol 51:1181–1187

    Article  CAS  Google Scholar 

  7. Suh J-W, Lee S-P, Park K-W, Lee H-Y, Kang H-J, Koo B-K, Cho Y-S, Youn T-J, Chae I-H, Choi D-J (2011) Multicenter randomized trial evaluating the efficacy of cilostazol on ischemic vascular complications after drug-eluting stent implantation for coronary heart disease: results of the CILON-T (influence of CILostazol-based triple antiplatelet therapy ON ischemic complication after drug-eluting stenT implantation) trial. J Am Coll Cardiol 57:280–289

    Article  CAS  Google Scholar 

  8. Lee S-W, Park S-W, Kim Y-H, Yun S-C, Park D-W, Lee CW, Kang S-J, Park S-J, Lee J-H, Choi SW (2011) A randomized, double-blind, multicenter comparison study of triple antiplatelet therapy with dual antiplatelet therapy to reduce restenosis after drug-eluting stent implantation in long coronary lesions: results from the DECLARE-LONG II (drug-eluting stenting followed by cilostazol treatment reduces late restenosis in patients with long coronary lesions) trial. J Am Coll Cardiol 57:1264–1270

    Article  CAS  Google Scholar 

  9. Gao W, Zhang Q, Ge H, Guo Y, Zhou Z (2013) Efficacy and safety of triple antiplatelet therapy in obese patients undergoing stent implantation. Angiology 64:554–558

    Article  Google Scholar 

  10. Youn YJ, Lee J-W, Ahn SG, Lee S-H, Choi H, Yu CW, Hong YJ, Kwon HM, Hong M-K, Jang Y (2014) Multicenter randomized trial of 3-month cilostazol use in addition to dual antiplatelet therapy after biolimus-eluting stent implantation for long or multivessel coronary artery disease. Am Heart J 167(241–248):e1

    Google Scholar 

  11. Wallentin L, Becker RC, Budaj A, Cannon CP, Emanuelsson H, Held C, Horrow J, Husted S, James S, Katus H, Mahaffey KW, Scirica BM, Skene A, Steg PG, Storey RF, Harrington RA, Freij A, Thorsen M (2009) Ticagrelor versus clopidogrel in patients with acute coronary syndromes. N Engl J Med 361:1045–1057

    Article  CAS  Google Scholar 

  12. Wiviott SD, Braunwald E, McCabe CH, Montalescot G, Ruzyllo W, Gottlieb S, Neumann F-J, Ardissino D, De Servi S, Murphy SA (2007) Prasugrel versus clopidogrel in patients with acute coronary syndromes. N Engl J Med 357:2001–2015

    Article  CAS  Google Scholar 

  13. 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; ESC Committee for Practice Guidelines (CPG); ESC National Cardiac Societies (2018) 2017 ESC focused update on dual antiplatelet therapy in coronary artery disease developed in collaboration with EACTS: The Task Force for dual antiplatelet therapy in coronary artery disease of the European Society of Cardiology (ESC) and of the European Association for Cardio-Thoracic Surgery (EACTS). Eur Heart J 39:213–260

    Article  Google Scholar 

  14. Levine GN, Bates ER, Bittl JA, Brindis RG, Fihn SD, Fleisher LA, Granger CB, Lange RA, Mack MJ, Mauri L (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: an update of the 2011 ACCF/AHA/SCAI guideline for percutaneous coronary intervention, 2011 ACCF/AHA guideline for coronary artery bypass graft surgery, 2012 ACC/AHA/ACP/AATS/PCNA/SCAI/STS guideline for the diagnosis and management of patients with stable ischemic heart disease, 2013 ACCF/AHA guideline for the management of ST-elevation myocardial infarction, 2014 AHA/ACC guideline for the management of patients with non–ST-elevation acute coronary syndromes, and 2014 ACC/AHA guideline on perioperative cardiovascular evaluation and management of patients undergoing noncardiac surgery. Circulation 134:e123–e155

    Article  Google Scholar 

  15. Ahn KT, Seong SW, Choi UL, Jin SA, Kim JH, Lee JH, Choi SW, Jeong MH, Chae SC, Kim YJ, Kim CJ, Kim HS, Cho MC, Gwon HC, Jeong JO, Seong IW (2019) Comparison of 1-year clinical outcomes between prasugrel and ticagrelor versus clopidogrel in type 2 diabetes patients with acute myocardial infarction underwent successful percutaneous coronary intervention. Medicine 98:e14833

    Article  CAS  Google Scholar 

  16. Kang J, Han JK, Ahn Y, Chae SC, Kim YJ, Chae IH, Hur SH, Seong IW, Chae JK, Cho MC, Seung KB, Jeong MH, Yang HM, Park KW, Kang HJ, Koo BK, Kim HS (2018) Third-generation P2Y12 inhibitors in East Asian acute myocardial infarction patients: a nationwide prospective multicentre study. Thromb Haemost 118:591–600

    Article  Google Scholar 

  17. Park KH, Jeong MH, Ahn Y, Ahn TH, Seung KB, Oh DJ, Choi DJ, Kim HS, Gwon HC, Seong IW, Hwang KK, Chae SC, Kim KB, Kim YJ, Cha KS, Oh SK, Chae JK (2016) Comparison of short-term clinical outcomes between ticagrelor versus clopidogrel in patients with acute myocardial infarction undergoing successful revascularization; from Korea Acute Myocardial Infarction Registry-National Institute of Health. Int J Cardiol 215:193–200

    Article  Google Scholar 

  18. Kimura K, Kimura T, Ishihara M, Nakagawa Y, Nakao K, Miyauchi K, Sakamoto T, Tsujita K, Hagiwara N, Miyazaki S, Ako J, Arai H, Ishii H, Origuchi H, Shimizu W, Takemura H, Tahara Y, Morino Y, Iino K, Itoh T, Iwanaga Y, Uchida K, Endo H, Kongoji K, Sakamoto K, Shiomi H, Shimohama T, Suzuki A, Takahashi J, Takeuchi I, Tanaka A, Tamura T, Nakashima T, Noguchi T, Fukamachi D, Mizuno T, Yamaguchi J, Yodogawa K, Kosuge M, Kohsaka S, Yoshino H, Yasuda S, Shimokawa H, Hirayama A, Akasaka T, Haze K, Ogawa H, Tsutsui H, Yamazaki T (2019) JCS 2018 guideline on diagnosis and treatment of acute coronary syndrome. Circ J 83:1085–1196

    Article  CAS  Google Scholar 

  19. Kang J, Kim H-S (2018) The evolving concept of dual antiplatelet therapy after percutaneous coronary intervention: focus on unique feature of East Asian and “Asian Paradox”. Korean Circ J 48:537–551

    Article  CAS  Google Scholar 

  20. Kim JH, Chae SC, Oh DJ, Kim HS, Kim YJ, Ahn Y, Cho MC, Kim CJ, Yoon JH, Park HY, Jeong MH, Korea Acute Myocardial Infarction-National Institutes of Health Registry Investigators (2016) Multicenter cohort study of acute myocardial infarction in Korea- interim analysis of the Korea acute myocardial infarction registry-national institutes of health registry. Circ J 80:1427–1436

    Article  Google Scholar 

  21. Jeong YH (2014) “East Asian paradox”: challenge for the current antiplatelet strategy of “one-guideline-fits-all races” in acute coronary syndrome. Curr Cardiol Rep 16:485

    Article  Google Scholar 

  22. Han S, Park G-M, Kim Y-G, Park M-W, Her SH, Lee S-W, Kim Y-H (2018) Trends, characteristics, and clinical outcomes of patients undergoing percutaneous coronary intervention in Korea between 2011 and 2015. Korean Circ J 48:310–321

    Article  Google Scholar 

  23. Schrör K (2002) The pharmacology of cilostazol. Diabetes Obes Metab 4(Suppl 2):S14–19

    Article  Google Scholar 

  24. Gresele P, Momi S, Falcinelli E (2011) Anti-platelet therapy: phosphodiesterase inhibitors. Br J Clin Pharmacol 72:634–646

    Article  CAS  Google Scholar 

  25. Guerra E, Byrne RA, Kastrati A (2014) Pharmacological inhibition of coronary restenosis: systemic and local approaches. Expert Opin Pharmacother 15:2155–2171

    Article  CAS  Google Scholar 

  26. Inoue T, Uchida T, Sakuma M, Imoto Y, Ozeki Y, Ozaki Y, Hikichi Y, Node K (2004) Cilostazol inhibits leukocyte integrin Mac-1, leading to a potential reduction in restenosis after coronary stent implantation. J Am Coll Cardiol 44:1408–1414

    Article  CAS  Google Scholar 

  27. Morishita R (2005) A scientific rationale for the CREST trial results: evidence for the mechanism of action of cilostazol in restenosis. Atheroscler Suppl 6:41–46

    Article  CAS  Google Scholar 

  28. Zou Y, Hu C, Ye W, Fan L, Xu L, Zhang A (2015) Long-term clinical efficacy and safety of adding cilostazol to dual antiplatelet therapy after drug-eluting stent implantation in coronary arteries: a meta-analysis of randomized controlled trials. Thromb Res 136:870–877

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This research was supported by a fund (#2016-ER6304-02) by the Research of Korea Centers for Disease Control and Prevention and Cardiovascular Intervention Research Institute Grant (#2019-CIRI001). This study was supported by the Korean Circulation Society (KCS) to commemorate the 50th Anniversary of KCS.

The KAMIR study group of the KSC was as follows: Myung Ho Jeong, Chonnam National University Hospital, Gwangju; Yong Hoon Kim, Kangwon National University School of Medicine, Chuncheon; Young Jo Kim, Yeungnam University Hospital, Daegu; Chong Jin Kim, East West Neo Medical Center, Seoul; Myeong Chan Cho, Chungbuk National University Hospital, Chungju; Youngkeun Ahn, Chonnam National University Hospital, Gwangju; Jong Hyun Kim, Hanseo Hospital, Busan; Shung Chull Chae, Kyungbook National University Hospital, Daegu; Seung Ho Hur, Keimyung University Dongsan Medical Center, Daegu; In Whan Seong, Chungnam National University Hospital, Daejeon; Taek Jong Hong, Pusan National University Hospital, Busan; Dong Hoon Choi, Yonsei Cardiovascular Center, Seoul; Jei Keon Chae, Chonbuk National University Hospital, Jeonju; Jae Young Rhew, Presbyterian Medical Center, Jeonju; Doo Il Kim, Inje University Busan Paik Hospital, Busan; In Ho Chae, Seoul National University Bundang Hospital, Seoul; Jung Han Yoon, Wonju Severance Christian Hospital, Wonju; Bon Kwon Koo, Seoul National University Hospital, Seoul; Byung Ok Kim, Inje University Sanggye Paik Hospital, Seoul; Myoung Yong Lee, Dankook University Hospital, Cheonan; Kee Sik Kim, Daegu Catholic University Medical Center, Daegu; Jin Yong Hwang, Gyeongsang National University Hospital, Jinju; Seok Kyu Oh, Wonkwang University Hospital, Iksan; Nae Hee Lee, Soon Chun Hyang University Hospital, Bucheon; Kyoung Tae Jeong, Eulji University Hospital, Daejeon; Seung Jea Tahk, Ajou University Hospital, Suwon; Jang Ho Bae, Konyang University Hospital, Daejeon; Seung-Woon Rha, Korea University Guro Hospital, Seoul; Keum Soo Park, Inha University Hospital, Incheon; Kyoo Rok Han, Hallym University Kangdong Medical Center, Seoul; Tae Hoon Ahn, Gachon University Gil Medical Center, Incheon; Moo Hyun Kim, Dong-A University Hospital, Busan; Joo Young Yang, National Health Insurance Service Ilsan Hospital, Goyang; Chong Yun Rhim, Hallym University Medical Center, Seoul; Hyeon Cheol Gwon, Samsung Medical Center, Seoul; Seong Wook Park, Asan Medical Center, Seoul; Young Youp Koh, Chosun University Hospital, Gwangju; Seung Jae Joo, Jeju National University Hospital, Jeju; Soo Joong Kim, Kyunghee University Medical Center, Seoul; Dong Kyu Jin, Soon Chun Hyang University Hospital, Cheonan; Jin Man Cho, Kyunghee University Hospital, Seoul; Wook Sung Chung, Catholic University Hospital, Seoul; Yang Soo Jang, Yonsei Cardiovascular Center, Seoul; Jeong Gwan Cho, Chonnam National University Hospital, Gwangju; Ki Bae Seung, Catholic University Hospital, Seoul; and Seung Jung Park, Asan Medical Center, Seoul.

Author information

Author notes

  1. Woohyeun Kim and Jin-Seok Kim contributed equally to this work.

Authors and Affiliations

  1. Cardiovascular Center, Korea University Guro Hospital, 148, Gurodong-ro, Guro-gu, Seoul, 08308, Republic of Korea

    Woohyeun Kim, Seung-Woon Rha, Won Young Jang, Dong Oh Kang, Yoonjee Park, Jah Yeon Choi, Seung-Young Roh, Jin Oh Na, Cheol Ung Choi, Eung Ju Kim, Chang Gyu Park, Hong Seog Seo, Se Yeon Choi, Jae Kyeong Byun & Jinah Cha

  2. Division of Cardiology, Department of Internal Medicine, Korea University Ansan Hospital, Ansan-si, Republic of Korea

    Jin-Seok Kim

  3. Cardiovascular Intervention Research Institute, Seoul, Republic of Korea

    Seung-Woon Rha & Dong Joo Oh

  4. College of Medicine, Institute of Health Science, Korea University, Seoul, Republic of Korea

    Byoung Geol Choi

  5. Heart Center of Chonnam, National University Hospital, Gwangju, Republic of Korea

    Myung Ho Jeong

Authors
  1. Woohyeun Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jin-Seok Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Seung-Woon Rha
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Byoung Geol Choi
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Won Young Jang
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Dong Oh Kang
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Yoonjee Park
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Jah Yeon Choi
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Seung-Young Roh
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Jin Oh Na
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Cheol Ung Choi
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Eung Ju Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Chang Gyu Park
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Hong Seog Seo
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Se Yeon Choi
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. Jae Kyeong Byun
    View author publications

    You can also search for this author in PubMed Google Scholar

  17. Jinah Cha
    View author publications

    You can also search for this author in PubMed Google Scholar

  18. Dong Joo Oh
    View author publications

    You can also search for this author in PubMed Google Scholar

  19. Myung Ho Jeong
    View author publications

    You can also search for this author in PubMed Google Scholar

Consortia

other Korea Acute Myocardial Infarction Registry (KAMIR) investigators

  • Myung Ho Jeong
  • , Yong Hoon Kim
  • , Young Jo Kim
  • , Chong Jin Kim
  • , Myeong Chan Cho
  • , Youngkeun Ahn
  • , Jong Hyun Kim
  • , Shung Chull Chae
  • , Seung Ho Hur
  • , In Whan Seong
  • , Taek Jong Hong
  • , Dong Hoon Choi
  • , Jei Keon Chae
  • , Jae Young Rhew
  • , Doo Il Kim
  • , In Ho Chae
  • , Jung Han Yoon
  • , Bon Kwon Koo
  • , Byung Ok Kim
  • , Myoung Yong Lee
  • , Kee Sik Kim
  • , Jin Yong Hwang
  • , Seok Kyu Oh
  • , Nae Hee Lee
  • , Kyoung Tae Jeong
  • , Seung Jea Tahk
  • , Jang Ho Bae
  • , Seung-Woon Rha
  • , Keum Soo Park
  • , Kyoo Rok Han
  • , Tae Hoon Ahn
  • , Moo Hyun Kim
  • , Joo Young Yang
  • , Chong Yun Rhim
  • , Hyeon Cheol Gwon
  • , Seong Wook Park
  • , Young Youp Koh
  • , Seung Jae Joo
  • , Soo Joong Kim
  • , Dong Kyu Jin
  • , Jin Man Cho
  • , Wook Sung Chung
  • , Yang Soo Jang
  • , Jeong Gwan Cho
  • , Ki Bae Seung
  •  & Seung Jung Park

Corresponding author

Correspondence to Seung-Woon Rha.

Ethics declarations

Conflict of interest

The authors have no financial conflicts of interest relevant to the manuscript to disclose.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

The members of the KAMIR study group are provided in the acknowledgements section.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kim, W., Kim, JS., Rha, SW. et al. Cilostazol-based triple versus potent P2Y12 inhibitor-based dual antiplatelet therapy in patients with acute myocardial infarction undergoing percutaneous coronary intervention. Heart Vessels 35, 1181–1192 (2020). https://doi.org/10.1007/s00380-020-01598-w

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00380-020-01598-w

Keywords

Search

Navigation