Korean Circulation Journal

The Korean Society of Cardiology (대한심장학회)
권호 표지
DOI QR코드

DOI QR Code

Prasugrel-based De-Escalation of Dual Antiplatelet Therapy After Percutaneous Coronary Intervention in Patients With STEMI

  • You-Jeong Ki (Cardiovascular Center, Department of Internal Medicine, Seoul National University Hospital) ;
  • Bong Ki Lee (Division of Cardiology, Department of Internal Medicine, Kangwon National University) ;
  • Kyung Woo Park (Cardiovascular Center, Department of Internal Medicine, Seoul National University Hospital) ;
  • Jang-Whan Bae (Division of Cardiology, Department of Internal Medicine, Chungbuk National University Hospital) ;
  • Doyeon Hwang (Cardiovascular Center, Department of Internal Medicine, Seoul National University Hospital) ;
  • Jeehoon Kang (Cardiovascular Center, Department of Internal Medicine, Seoul National University Hospital) ;
  • Jung-Kyu Han (Cardiovascular Center, Department of Internal Medicine, Seoul National University Hospital) ;
  • Han-Mo Yang (Cardiovascular Center, Department of Internal Medicine, Seoul National University Hospital) ;
  • Hyun-Jae Kang (Cardiovascular Center, Department of Internal Medicine, Seoul National University Hospital) ;
  • Bon-Kwon Koo (Cardiovascular Center, Department of Internal Medicine, Seoul National University Hospital) ;
  • Dong-Bin Kim (Division of Cardiology, Department of Internal Medicine, Bucheon St. Mary's Hospital) ;
  • In-Ho Chae (Division of Cardiology, Department of Internal Medicine, Seoul National University Bundang Hospital) ;
  • Keon-Woong Moon (Division of Cardiology, Department of Internal Medicine, St. Vincent's Hospital) ;
  • Hyun Woong Park (Division of Cardiology, Department of Internal Medicine, Gyeongsang National University Hospital) ;
  • Ki-Bum Won (Division of Cardiology, Department of Internal Medicine, Ulsan University Hospital) ;
  • Dong Woon Jeon (Division of Cardiology, Department of Internal Medicine, National Health Insurance Service Ilsan Hospital) ;
  • Kyoo-Rok Han (Division of Cardiology, Department of Internal Medicine, Kangdong Sacred Heart Hospital) ;
  • Si Wan Choi (Division of Cardiology, Department of Internal Medicine, Chungnam National University Hospital) ;
  • Jae Kean Ryu (Division of Cardiology, Department of Internal Medicine, Daegu Catholic University Medical Center) ;
  • Myung Ho Jeong (Division of Cardiology, Department of Internal Medicine, Chonnam National University Hospital) ;
  • Kwang Soo Cha (Division of Cardiology, Department of Internal Medicine, Pusan National University Hospital) ;
  • Hyo-Soo Kim (Cardiovascular Center, Department of Internal Medicine, Seoul National University Hospital) ;
  • HOST-RP-ACS investigators (HOST-RP-ACS)
  • Received : 2021.08.30
  • Accepted : 2021.12.01
  • Published : 2022.04.01
Download PDF
⟨ Previous Next ⟩

Abstract

Background and Objectives: De-escalation of dual-antiplatelet therapy through dose reduction of prasugrel improved net adverse clinical events (NACEs) after acute coronary syndrome (ACS), mainly through the reduction of bleeding without an increase in ischemic outcomes. Whether the benefits of de-escalation are sustained in highly thrombotic conditions such as ST-elevation myocardial infarction (STEMI) is unknown. We aimed to assess the efficacy and safety of de-escalation therapy in patients with STEMI or non-ST-segment elevation ACS (NSTE-ACS). Methods: This is a pre-specified subgroup analysis of the HOST-REDUCE-POLYTECH-ACS trial. ACS patients were randomized to prasugrel de-escalation (5 mg daily) or conventional dose (10 mg daily) at 1-month post-percutaneous coronary intervention. The primary endpoint was a NACE, defined as a composite of all-cause death, non-fatal myocardial infarction, stent thrombosis, clinically driven revascularization, stroke, and bleeding events of grade ≥2 Bleeding Academic Research Consortium (BARC) criteria at 1 year. Results: Among 2,338 patients included in the randomization, 326 patients were diagnosed with STEMI. In patients with NSTE-ACS, the risk of the primary endpoint was significantly reduced with de-escalation (hazard ratio [HR], 0.65; 95% confidence interval [CI], 0.48-0.89; p=0.006 for de-escalation vs. conventional), mainly driven by a reduced bleeding. However, in those with STEMI, there was no difference in the occurrence of the primary outcome (HR, 1.04; 95% CI, 0.48-2.26; p=0.915; p for interaction=0.271). Conclusions: Prasugrel dose de-escalation reduced the rate of NACE and bleeding, without increasing the rate of ischemic events in NSTE-ACS patients but not in STEMI patients.

Keywords

Acknowledgement

This study was funded by Daiichi Sankyo, Boston Scientific, Terumo, Biotronik, Qualitech Korea, and Dio. This research was partially supported by a grant from Seoul National University Hospital (Research ID: 03-2021-0030). The funders of this study had no role in study design, collection of data and data analysis, or writing of the manuscript.

References

  1. Neumann FJ, Sousa-Uva M, Ahlsson A, et al. 2018 ESC/EACTS guidelines on myocardial revascularization. Eur Heart J 2019;40:87-165. https://doi.org/10.1093/eurheartj/ehy394
  2. Wallentin L, Becker RC, Budaj A, et al. Ticagrelor versus clopidogrel in patients with acute coronary syndromes. N Engl J Med 2009;361:1045-57. https://doi.org/10.1056/NEJMoa0904327
  3. Wiviott SD, Braunwald E, McCabe CH, et al. Prasugrel versus clopidogrel in patients with acute coronary syndromes. N Engl J Med 2007;357:2001-15. https://doi.org/10.1056/NEJMoa0706482
  4. Kang J, Park KW, Ki YJ, et al. Development and validation of an ischemic and bleeding risk evaluation tool in East Asian patients receiving percutaneous coronary intervention. Thromb Haemost 2019;119:1182-93. https://doi.org/10.1055/s-0039-1688792
  5. Kang J, Park KW, Palmerini T, et al. Racial differences in ischaemia/bleeding risk trade-off during anti-platelet therapy: individual patient level landmark meta-analysis from seven RCTs. Thromb Haemost 2019;119:149-62. https://doi.org/10.1055/s-0038-1676545
  6. Ki YJ, Kang J, Park J, et al. Efficacy and safety of long-term and short-term dual antiplatelet therapy: a meta-analysis of comparison between Asians and non-Asians. J Clin Med 2020;9:652.
  7. Valgimigli M, Costa F, Lokhnygina Y, et al. Trade-off of myocardial infarction vs. bleeding types on mortality after acute coronary syndrome: lessons from the Thrombin Receptor Antagonist for Clinical Event Reduction in Acute Coronary Syndrome (TRACER) randomized trial. Eur Heart J 2017;38:804-10.
  8. Costa F, van Klaveren D, James S, et al. Derivation and validation of the predicting bleeding complications in patients undergoing stent implantation and subsequent dual antiplatelet therapy (PRECISE-DAPT) score: a pooled analysis of individual-patient datasets from clinical trials. Lancet 2017;389:1025-34. https://doi.org/10.1016/S0140-6736(17)30397-5
  9. Kim HS, Kang J, Hwang D, et al. Prasugrel-based de-escalation of dual antiplatelet therapy after percutaneous coronary intervention in patients with acute coronary syndrome (HOST-REDUCEPOLYTECH-ACS): an open-label, multicentre, non-inferiority randomised trial. Lancet 2020;396:1079-89. https://doi.org/10.1016/S0140-6736(20)31791-8
  10. Franchi F, Rollini F, Angiolillo DJ. Antithrombotic therapy for patients with STEMI undergoing primary PCI. Nat Rev Cardiol 2017;14:361-79. https://doi.org/10.1038/nrcardio.2017.18
  11. Lee JM, Jung JH, Park KW, et al. Harmonizing Optimal Strategy for Treatment of coronary artery diseases--comparison of REDUCtion of prasugrEl dose or POLYmer TECHnology in ACS patients (HOST-REDUCE-POLYTECH-ACS RCT): study protocol for a randomized controlled trial. Trials 2015;16:409.
  12. Kim HS, Kang J, Hwang D, et al. Durable polymer versus biodegradable polymer drug-eluting stents after percutaneous coronary intervention in patients with acute coronary syndrome: the HOST-REDUCE-POLYTECH-ACS trial. Circulation 2021;143:1081-91. https://doi.org/10.1161/CIRCULATIONAHA.120.051700
  13. Garcia-Garcia HM, McFadden EP, Farb A, et al. Standardized end point definitions for coronary intervention trials: the Academic Research Consortium-2 consensus document. Circulation 2018;137:2635-50. https://doi.org/10.1161/CIRCULATIONAHA.117.029289
  14. Montalescot G, Wiviott SD, Braunwald E, et al. Prasugrel compared with clopidogrel in patients undergoing percutaneous coronary intervention for ST-elevation myocardial infarction (TRITON-TIMI 38): double-blind, randomised controlled trial. Lancet 2009;373:723-31. https://doi.org/10.1016/S0140-6736(09)60441-4
  15. Steg PG, James S, Harrington RA, et al. Ticagrelor versus clopidogrel in patients with ST-elevation acute coronary syndromes intended for reperfusion with primary percutaneous coronary intervention: a Platelet Inhibition and Patient Outcomes (PLATO) trial subgroup analysis. Circulation 2010;122:2131-41. https://doi.org/10.1161/CIRCULATIONAHA.109.927582
  16. Udell JA, Braunwald E, Antman EM, Murphy SA, Montalescot G, Wiviott SD. Prasugrel versus clopidogrel in patients with ST-segment elevation myocardial infarction according to timing of percutaneous coronary intervention: a TRITON-TIMI 38 subgroup analysis (Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition with Prasugrel-Thrombolysis In Myocardial Infarction 38). JACC Cardiovasc Interv 2014;7:604-12. https://doi.org/10.1016/j.jcin.2014.01.160
  17. Velders MA, Abtan J, Angiolillo DJ, et al. Safety and efficacy of ticagrelor and clopidogrel in primary percutaneous coronary intervention. Heart 2016;102:617-25. https://doi.org/10.1136/heartjnl-2015-308963
  18. Kim BK, Hong SJ, Cho YH, et al. Effect of ticagrelor monotherapy vs ticagrelor with aspirin on major bleeding and cardiovascular events in patients with acute coronary syndrome: the TICO randomized clinical trial. JAMA 2020;323:2407-16. https://doi.org/10.1001/jama.2020.7580
  19. Lee SJ, Cho JY, Kim BK, et al. Ticagrelor monotherapy versus ticagrelor with aspirin in patients with ST-segment elevation myocardial infarction. JACC Cardiovasc Interv 2021;14:431-40. https://doi.org/10.1016/j.jcin.2020.11.036
  20. Kupka D, Sibbing D. De-escalation of P2Y12 receptor inhibitor therapy after acute coronary syndromes in patients undergoing percutaneous coronary intervention. Korean Circ J 2018;48:863-72. https://doi.org/10.4070/kcj.2018.0255
  21. Lee HS, Park KW, Kang J, Han JK, Kim HS. De-escalation of prasugrel results in higher percentage of patients within optimal range of platelet reactivity. Thromb Haemost. 2021 [Epub ahead of print].
  22. Mehran R, Baber U, Sharma SK, et al. Ticagrelor with or without aspirin in high-risk patients after PCI. N Engl J Med 2019;381:2032-42. https://doi.org/10.1056/NEJMoa1908419
  23. Hahn JY, Song YB, Oh JH, et al. 6-month versus 12-month or longer dual antiplatelet therapy after percutaneous coronary intervention in patients with acute coronary syndrome (SMART-DATE): a randomised, open-label, non-inferiority trial. Lancet 2018;391:1274-84. https://doi.org/10.1016/S0140-6736(18)30493-8
  24. Bonaca MP, Bhatt DL, Cohen M, et al. Long-term use of ticagrelor in patients with prior myocardial infarction. N Engl J Med 2015;372:1791-800. https://doi.org/10.1056/NEJMoa1500857