Skip to main content
Log in

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

  • Evidence-Based Medicine, Clinical Trials and Their Interpretations (L. Roever, Section Editor)
  • Published:
Current Atherosclerosis Reports Aims and scope Submit manuscript

Abstract

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.

Summary

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.

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

Access this article

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

Instant access to the full article PDF.

Fig. 1

Similar content being viewed by others

References

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

  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.

    Article  Google Scholar 

  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.

    Article  Google Scholar 

  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.

    Article  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  5. Libby P. Mechanisms of acute coronary syndromes and their implications for therapy. N Engl J Med. 2013;368(21):2004–13.

    Article  CAS  Google Scholar 

  6. Davi G, Patrono C. Platelet activation and atherothrombosis. N Engl J Med. 2007;357(24):2482–94.

    Article  CAS  Google Scholar 

  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.

    Article  Google Scholar 

  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.

    Article  Google Scholar 

  9. Angiolillo DJ, Ueno M, Goto S. Basic principles of platelet biology and clinical implications. Circ J. 2010;74(4):597–607.

    Article  CAS  Google Scholar 

  10. Franchi F, Angiolillo DJ. Novel antiplatelet agents in acute coronary syndrome. Nat Rev Cardiol. 2015;12(1):30–47.

    Article  CAS  Google Scholar 

  11. Brummel KE, Paradis SG, Butenas S, Mann KG. Thrombin functions during tissue factor-induced blood coagulation. Blood. 2002;100(1):148–52.

    Article  CAS  Google Scholar 

  12. Angiolillo DJ, Capodanno D, Goto S. Platelet thrombin receptor antagonism and atherothrombosis. Eur Heart J. 2010;31(1):17–28.

    Article  CAS  Google Scholar 

  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.

    Article  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

  18. Franchi F, Rollini F, Angiolillo DJ. Antithrombotic therapy for patients with STEMI undergoing primary PCI. Nat Rev Cardiol. 2017;14(6):361–79.

    Article  CAS  Google Scholar 

  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).

  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.

    Article  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  Google Scholar 

  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.

    Article  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  32. Capodanno D, Angiolillo DJ. Aspirin for primary cardiovascular risk prevention and beyond in diabetes mellitus. Circulation. 2016;134(20):1579–94.

    Article  CAS  Google Scholar 

  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.

    Article  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  Google Scholar 

  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.

    Article  Google Scholar 

  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.

    Article  CAS  Google Scholar 

Download references

Funding

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).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Qingchun Zeng.

Ethics declarations

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.

Additional information

Publisher’s Note

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

This article is part of the Topical Collection on Evidence-Based Medicine, Clinical Trials and Their Interpretations

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Tu, Y., Hu, L., Yang, C. et al. Optimal Antithrombotic Therapy for Patients with STEMI Undergoing PCI at High Risk of Bleeding. Curr Atheroscler Rep 21, 22 (2019). https://doi.org/10.1007/s11883-019-0782-x

Download citation

  • Published:

  • DOI: https://doi.org/10.1007/s11883-019-0782-x

Keywords

Navigation