Optimal Antithrombotic Therapy for Patients with STEMI Undergoing PCI at High Risk of Bleeding

  • Yan Tu
  • Lu Hu
  • Chanjuan Yang
  • Arash Nemat
  • Gaopeng Xian
  • Jierong Zhang
  • Qingchun ZengEmail author
Evidence-Based Medicine, Clinical Trials and Their Interpretations (L. Roever, Section Editor)
Part of the following topical collections:
  1. Topical Collection on Evidence-Based Medicine, Clinical Trials and Their Interpretations


Purpose of Review

In the review, we briefly describe antithrombotic drugs and the use evidence from evidence-based medicine to elucidate the optimal antithrombotic management for patients with ST-segment elevation myocardial infarction (STEMI) undergoing percutaneous coronary stenting (PCI) at high risk of bleeding.

Recent Findings

Mandatory use of intravenous anticoagulants and dual antiplatelet agents is the cornerstone strategy in acute and long-term antithrombotic management to optimize the clinical benefit of patients with STEMI undergoing PCI. Nevertheless, with the increasing occurrence of STEMI in old population with high risk of bleeding and renal insufficiency, as well as the specificity of high bleeding risk groups, the optimization of antithrombotic therapy still remains uncertain.


Bivalirudin is the optimized intravenous anticoagulant agent for these patients based on the guideline recommendations and clinic data. Timely and potent ticagrelor and prasugrel with aspirin usage can increase the clinical benefit for the patients without increasing the clinical bleeding risk. At present, the multi-center, prospective clinical studies of EVOLVE short DAPT, MASTER DAPT, and POEM trials, targeting patients with high risk of bleeding, are in experimental stage. These clinical trials will provide more objective and optimal antithrombotic management strategy for the patients.


Antithrombotic therapy Acute ST-segment elevation myocardial infarction (STEMI) Percutaneous coronary intervention (PCI) High risk of bleeding Bivalirudin 


Funding Information

The authors are funded by the National Natural Science Foundation Program of China (81700388, 81770386, and 399281570352), the Major Scientific Research Foundation of Colleges and Universities of Guangdong Province (2016KZDXM016), Frontier Research Program of Guangzhou Regenerative Medicine and Health Guangdong Laboratory (2018GZR110105001), and the Clinical Training Project Foundation of Southern Medical University (No. LC2016PY002).

Compliance with Ethical Standards

Conflict of Interest

Yan Tu, Lu Hu, Chanjuan Yang, Arash Nemat, Gaopeng Xian, Jierong Zhang, and Qingchun Zeng declare no conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.


Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. 1.
    O’Gara PT, Kushner FG, Ascheim DD, Casey DE Jr, Chung MK, de Lemos JA, et al. 2013 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.CrossRefGoogle Scholar
  2. 2.
    • Ibanez B, James S, Agewall S, Antunes MJ, Bucciarelli-Ducci C, Bueno H, et al. 2017 ESC guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation: the Task Force for the management of acute myocardial infarction in patients presenting with ST-segment elevation of the European Society of Cardiology (ESC). Eur Heart J. 2018;39(2):119–77. An important latest guideline for the management of acute myocardial infarction in patients presenting with ST-segment elevation. CrossRefGoogle Scholar
  3. 3.
    Windecker S, Kolh P, Alfonso F, Collet JP, Cremer J, Falk V, et al. 2014 ESC/EACTS guidelines on myocardial revascularization: the task force on myocardial revascularization of the European Society of Cardiology (ESC) and the European Association for Cardio-Thoracic Surgery (EACTS) developed with the special contribution of the European Association of Percutaneous Cardiovascular Interventions (EAPCI). Eur Heart J. 2014;35(37):2541–619.CrossRefGoogle Scholar
  4. 4.
    Falk E, Nakano M, Bentzon JF, Finn AV, Virmani R. Update on acute coronary syndromes: the pathologists’ view. Eur Heart J. 2013;34(10):719–28.CrossRefGoogle Scholar
  5. 5.
    Libby P. Mechanisms of acute coronary syndromes and their implications for therapy. N Engl J Med. 2013;368(21):2004–13.CrossRefGoogle Scholar
  6. 6.
    Davi G, Patrono C. Platelet activation and atherothrombosis. N Engl J Med. 2007;357(24):2482–94.CrossRefGoogle Scholar
  7. 7.
    Alexander KP, Newby LK, Cannon CP, Armstrong PW, Gibler WB, Rich MW, et al. Acute coronary care in the elderly, part I: non-ST-segment-elevation acute coronary syndromes: a scientific statement for healthcare professionals from the American Heart Association Council on Clinical Cardiology: in collaboration with the Society of Geriatric Cardiology. Circulation. 2007;115(19):2549–69.CrossRefGoogle Scholar
  8. 8.
    Michaels AD, Spinler SA, Leeper B, Ohman EM, Alexander KP, Newby LK, et al. Medication errors in acute cardiovascular and stroke patients: a scientific statement from the American Heart Association. Circulation. 2010;121(14):1664–82.CrossRefGoogle Scholar
  9. 9.
    Angiolillo DJ, Ueno M, Goto S. Basic principles of platelet biology and clinical implications. Circ J. 2010;74(4):597–607.CrossRefGoogle Scholar
  10. 10.
    Franchi F, Angiolillo DJ. Novel antiplatelet agents in acute coronary syndrome. Nat Rev Cardiol. 2015;12(1):30–47.CrossRefGoogle Scholar
  11. 11.
    Brummel KE, Paradis SG, Butenas S, Mann KG. Thrombin functions during tissue factor-induced blood coagulation. Blood. 2002;100(1):148–52.CrossRefGoogle Scholar
  12. 12.
    Angiolillo DJ, Capodanno D, Goto S. Platelet thrombin receptor antagonism and atherothrombosis. Eur Heart J. 2010;31(1):17–28.CrossRefGoogle Scholar
  13. 13.
    Nikolsky E, Mehran R, Dangas G, Fahy M, Na Y, Pocock SJ, et al. Development and validation of a prognostic risk score for major bleeding in patients undergoing percutaneous coronary intervention via the femoral approach. Eur Heart J. 2007;28(16):1936–45.CrossRefGoogle Scholar
  14. 14.
    •• Urban P, Meredith IT, Abizaid A, Pocock SJ, Carrie D, Naber C, et al. Polymer-free drug-coated coronary stents in patients at high bleeding risk. N Engl J Med. 2015;373(21):2038–47. An important randomized controlled study showing the definition of patient with STEMI at high risk of bleeding. CrossRefGoogle Scholar
  15. 15.
    Boneu B, Caranobe C, Cadroy Y, Dol F, Gabaig AM, Dupouy D, et al. Pharmacokinetic studies of standard unfractionated heparin, and low molecular weight heparins in the rabbit. Semin Thromb Hemost. 1988;14(1):18–27.CrossRefGoogle Scholar
  16. 16.
    Palm M, Mattsson C. Pharmacokinetics of heparin and low molecular weight heparin fragment (Fragmin) in rabbits with impaired renal or metabolic clearance. Thromb Haemost. 1987;58(3):932–5.CrossRefGoogle Scholar
  17. 17.
    Sousa-Uva M, Neumann FJ, Ahlsson A, Alfonso F, Banning AP, Benedetto U, et al. 2018 ESC/EACTS guidelines on myocardial revascularization. Eur J Cardiothorac Surg 2019 Jan 1;55(1):4–90.Google Scholar
  18. 18.
    Franchi F, Rollini F, Angiolillo DJ. Antithrombotic therapy for patients with STEMI undergoing primary PCI. Nat Rev Cardiol. 2017;14(6):361–79.CrossRefGoogle Scholar
  19. 19.
    Fahrni G, Wolfrum M, De Maria GL, Banning AP, Benedetto U, Kharbanda RK. Prolonged high-dose bivalirudin infusion reduces major bleeding without increasing stent thrombosis in patients undergoing primary percutaneous coronary intervention: novel insights from an updated meta-analysis. J Am Heart Assoc. 2016;5(7).Google Scholar
  20. 20.
    •• Leonardi S, Frigoli E, Rothenbuhler M, Navarese E, Calabro P, Bellotti P, et al. Bivalirudin or unfractionated heparin in patients with acute coronary syndromes managed invasively with and without ST elevation (MATRIX): randomised controlled trial. BMJ. 2016;354:i4935. An important randomized clinical trial confirming that the bivalirudin is the optimal intravenous anticoagulant therapy for patients with STEMI at high risk of bleeding based on the subgroup analysis. CrossRefGoogle Scholar
  21. 21.
    Lopes RD, Alexander KP, Manoukian SV, Bertrand ME, Feit F, White HD, et al. Advanced age, antithrombotic strategy, and bleeding in non-ST-segment elevation acute coronary syndromes: results from the ACUITY (Acute Catheterization and Urgent Intervention Triage Strategy) trial. J Am Coll Cardiol. 2009;53(12):1021–30.CrossRefGoogle Scholar
  22. 22.
    Erlinge D, Omerovic E, Frobert O, Linder R, Danielewicz M, Hamid M, et al. Bivalirudin versus heparin monotherapy in myocardial infarction. N Engl J Med. 2017;377(12):1132–42.CrossRefGoogle Scholar
  23. 23.
    Shahzad A, Kemp I, Mars C, Wilson K, Roome C, Cooper R, et al. Unfractionated heparin versus bivalirudin in primary percutaneous coronary intervention (HEAT-PPCI): an open-label, single centre, randomised controlled trial. Lancet. 2014;384(9957):1849–58.CrossRefGoogle Scholar
  24. 24.
    Muniz-Lozano A, Rollini F, Franchi F, Angiolillo DJ. Update on platelet glycoprotein IIb/IIIa inhibitors: recommendations for clinical practice. Ther Adv Cardiovasc Dis. 2013;7(4):197–213.CrossRefGoogle Scholar
  25. 25.
    De Luca G, Suryapranata H, Stone GW, Antoniucci D, Tcheng JE, Neumann FJ, et al. Abciximab as adjunctive therapy to reperfusion in acute ST-segment elevation myocardial infarction: a meta-analysis of randomized trials. JAMA. 2005;293(14):1759–65.CrossRefGoogle Scholar
  26. 26.
    Eitel I, Franke A, Schuler G, Thiele H. ST-segment resolution and prognosis after facilitated versus primary percutaneous coronary intervention in acute myocardial infarction: a meta-analysis. Clin Res Cardiol. 2010;99(1):1–11.CrossRefGoogle Scholar
  27. 27.
    Ellis SG, Tendera M, de Belder MA, van Boven AJ, Widimsky P, Janssens L, et al. Facilitated PCI in patients with ST-elevation myocardial infarction. N Engl J Med. 2008;358(21):2205–17.CrossRefGoogle Scholar
  28. 28.
    Stone GW, Witzenbichler B, Guagliumi G, Peruga JZ, Brodie BR, Dudek D, et al. Bivalirudin during primary PCI in acute myocardial infarction. N Engl J Med. 2008;358(21):2218–30.CrossRefGoogle Scholar
  29. 29.
    Mehran R, Pocock SJ, Stone GW, Clayton TC, Dangas GD, Feit F, et al. Associations of major bleeding and myocardial infarction with the incidence and timing of mortality in patients presenting with non-ST-elevation acute coronary syndromes: a risk model from the ACUITY trial. Eur Heart J. 2009;30(12):1457–66.CrossRefGoogle Scholar
  30. 30.
    Stone GW, Witzenbichler B, Guagliumi G, Peruga JZ, Brodie BR, Dudek D, et al. Heparin plus a glycoprotein IIb/IIIa inhibitor versus bivalirudin monotherapy and paclitaxel-eluting stents versus bare-metal stents in acute myocardial infarction (HORIZONS-AMI): final 3-year results from a multicentre, randomised controlled trial. Lancet. 2011;377(9784):2193–204.CrossRefGoogle Scholar
  31. 31.
    Patrono C, Garcia Rodriguez LA, Landolfi R, Baigent C. Low-dose aspirin for the prevention of atherothrombosis. N Engl J Med. 2005;353(22):2373–83.CrossRefGoogle Scholar
  32. 32.
    Capodanno D, Angiolillo DJ. Aspirin for primary cardiovascular risk prevention and beyond in diabetes mellitus. Circulation. 2016;134(20):1579–94.CrossRefGoogle Scholar
  33. 33.
    Kedhi E, Fabris E, van der Ent M, Buszman P, von Birgelen C, Roolvink V, et al. Six months versus 12 months dual antiplatelet therapy after drug-eluting stent implantation in ST-elevation myocardial infarction (DAPT-STEMI): randomised, multicentre, non-inferiority trial. BMJ. 2018;363:k3793.CrossRefGoogle Scholar
  34. 34.
    Sabatine MS, Cannon CP, Gibson CM, Lopez-Sendon JL, Montalescot G, Theroux P, et al. Addition of clopidogrel to aspirin and fibrinolytic therapy for myocardial infarction with ST-segment elevation. N Engl J Med. 2005;352(12):1179–89.CrossRefGoogle Scholar
  35. 35.
    Chen ZM, Jiang LX, Chen YP, Xie JX, Pan HC, Peto R, et al. Addition of clopidogrel to aspirin in 45,852 patients with acute myocardial infarction: randomised placebo-controlled trial. Lancet. 2005;366(9497):1607–21.CrossRefGoogle Scholar
  36. 36.
    Angiolillo DJ, Fernandez-Ortiz A, Bernardo E, Alfonso F, Macaya C, Bass TA, et al. Variability in individual responsiveness to clopidogrel: clinical implications, management, and future perspectives. J Am Coll Cardiol. 2007;49(14):1505–16.CrossRefGoogle Scholar
  37. 37.
    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.CrossRefGoogle Scholar
  38. 38.
    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.CrossRefGoogle Scholar
  39. 39.
    • Montalescot G, Wiviott SD, Braunwald E, Murphy SA, Gibson CM, McCabe CH, 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(9665):723–31. An important randomized clinical trial showing prasugrel is the superior oral antiplatelet drug for patients with STEMI at high risk of bleeding based on the analysis above. CrossRefGoogle Scholar
  40. 40.
    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). J Am Coll Cardiol Intv. 2014;7(6):604–12.CrossRefGoogle Scholar
  41. 41.
    • Steg PG, James S, Harrington RA, Ardissino D, Becker RC, Cannon CP, 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(21):2131–41. An important randomized clinical trial showing ticagrelor is the superior oral antiplatelet drug for patients with STEMI at high risk of bleeding based on the analysis above. CrossRefGoogle Scholar
  42. 42.
    •• Velders MA, Abtan J, Angiolillo DJ, Ardissino D, Harrington RA, Hellkamp A, et al. Safety and efficacy of ticagrelor and clopidogrel in primary percutaneous coronary intervention. Heart. 2016;102(8):617–25. An important post-hoc subgroup analysis showing ticagrelor is the superior oral antiplatelet drug for patients with STEMI at high risk of bleeding.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Yan Tu
    • 1
  • Lu Hu
    • 2
  • Chanjuan Yang
    • 3
  • Arash Nemat
    • 1
  • Gaopeng Xian
    • 1
    • 4
  • Jierong Zhang
    • 1
  • Qingchun Zeng
    • 1
    • 4
    Email author
  1. 1.Department of Cardiology,State Key Laboratory of Organ Failure Research, Nanfang HospitalSouthern Medical UniversityGuangzhouPeople’s Republic of China
  2. 2.Department of CardiologyThe First People’s Hospital of ChenzhouChenzhouPeople’s Republic of China
  3. 3.Department of Oncology, Nanfang HospitalSouthern Medical UniversityGuangzhouPeople’s Republic of China
  4. 4.Guangzhou Regenerative Medicine and Health Guangdong LaboratoryGuangzhouChina

Personalised recommendations