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Percutaneous Coronary Intervention: Adjunctive Pharmacology

  • Paul A. Gurbel
  • Udaya S. Tantry
Chapter

Abstract

Percutaneous coronary intervention (PCI) promotes thrombosis by inducing extreme vascular injury. The concomitant presence of dysfunctional endothelium, vulnerable plaque, and endothelial erosion promotes further thrombotic risk. Platelet adhesion to newly exposed collagen and von Willebrand factor by specific receptors and binding of thrombin generated by tissue factor to protease-activated receptors (PARs) cause initial platelet activation. Following activation, adenosine diphosphate (ADP) is released from dense granules and thromboxane A2 is generated by cyclooxygenase-1 (COX-1). Although both thromboxane A2 and ADP amplify platelet activation and aggregation, continuous ADP-P2Y12 receptor signaling is essential for sustained activation of the GPIIb/IIIa receptor and stable thrombus generation. Simultaneously, platelet activation exposes the phosphatidylserine surface providing binding sites for coagulation factors and the generation of thrombin. Thrombin converts fibrinogen to fibrin and activates factor XIII that cross-links the fibrin network, stabilizes the platelet-fibrin clot at the site of vascular injury, and impairs myocardial blood supply. Therefore, the rationale for antithrombotic therapy during and following PCI is to prevent thrombus formation within the target lesion and also in nontarget vessels by attenuating platelet activation and aggregation and arresting coagulation processes. Since clot formation involves multiple pathways including platelet activation and aggregation and coagulation, simultaneous blockade of these pathways is essential to prevent periprocedural and post-PCI ischemic event occurrences. Optimal inhibition of these pathways is essential for maximizing antithrombotic effects and minimizing bleeding risk and is critically dependent on individual patient risk.

Keywords

Antiplatelet Antithrombotic Platelet Aspirin Clopidogrel Ticagrelor Prasugrel Glycoprotein inhibitor Heparin Bivalirudin 

References

  1. 1.
    Tantry US, Etherington A, Bliden KP, Gurbel PA. Antiplatelet therapy: current strategies and future trends. Future Cardiol. 2006;2:343–66.CrossRefPubMedGoogle Scholar
  2. 2.
    Gurbel PA, Tantry US. Antiplatelet and anticoagulant agents in heart failure: current status and future perspectives. JACC Heart Fail. 2014;2:1–14.CrossRefPubMedGoogle Scholar
  3. 3.
    Mehta SR, Tanguay JF, Eikelboom JW, et al. CURRENT-OASIS 7 trial investigators. Double-dose versus standard-dose clopidogrel and high-dose versus low-dose aspirin in individuals undergoing percutaneous coronary intervention for acute coronary syndromes (CURRENT-OASIS 7): a randomised factorial trial. Lancet. 2010;376:1233–43.CrossRefPubMedGoogle Scholar
  4. 4.
    Windecker S, Kolh P, Alfonso F, 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;35:2541–619.CrossRefPubMedGoogle Scholar
  5. 5.
    Roffi M, Patrono C, Collet JP, et al. Management of Acute Coronary Syndromes in Patients Presenting without Persistent ST-Segment Elevation of the European Society of Cardiology. 2015 ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation: Task Force for the Management of Acute Coronary Syndromes in Patients Presenting without Persistent ST-Segment Elevation of the European Society of Cardiology (ESC). Eur Heart J. 2016;37:267–315.CrossRefPubMedGoogle Scholar
  6. 6.
    Steg PG, James SK, Atar D, et al. ESC Guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation. Eur Heart J. 2012;33:2569–619.CrossRefPubMedGoogle Scholar
  7. 7.
    Tantry US, Bonello L, Aradi D, et al. Working Group on On-Treatment Platelet Reactivity. Consensus and update on the definition of on-treatment platelet reactivity to adenosine diphosphate associated with ischemia and bleeding. J Am Coll Cardiol. 2013;62:2261–73.CrossRefPubMedGoogle Scholar
  8. 8.
    Wiviott SD, Braunwald E, McCabe CH, et al. TRITON-TIMI 38 Investigators. Prasugrel versus clopidogrel in patients with acute coronary syndromes. N Engl J Med. 2007;357:2001–15.CrossRefPubMedGoogle Scholar
  9. 9.
    Montalescot G, Bolognese L, Dudek D, et al. ACCOAST Investigators. Pretreatment with prasugrel in non-ST-segment elevation acute coronary syndromes. N Engl J Med. 2013;369:999–1010.CrossRefPubMedGoogle Scholar
  10. 10.
    Gurbel PA, Bliden KP, Butler K, et al. Randomized double-blind assessment of the ONSET and OFFSET of the antiplatelet effects of ticagrelor versus clopidogrel in patients with stable coronary artery disease: the ONSET/OFFSET study. Circulation. 2009;120:2577–85.CrossRefPubMedGoogle Scholar
  11. 11.
    Cannon CP, Harrington RA, James S, et al. PLATelet Inhibition and Patient Outcomes Investigators. Comparison of ticagrelor with clopidogrel in patients with a planned invasive strategy for acute coronary syndromes (PLATO): a randomised double-blind study. Lancet. 2010;375:283–93.CrossRefPubMedGoogle Scholar
  12. 12.
    Montalescot G, van ‘t Hof AW, Lapostolle F, et al. ATLANTIC Investigators. Prehospital ticagrelor in ST-segment elevation myocardial infarction. N Engl J Med. 2014;371:1016–27.CrossRefPubMedGoogle Scholar
  13. 13.
    Bhatt DL, Stone GW, Mahaffey KW, et al. CHAMPION PHOENIX Investigators. Effect of platelet inhibition with cangrelor during PCI on ischemic events. N Engl J Med. 2013;368:1303–13.CrossRefPubMedGoogle Scholar
  14. 14.
    Lefkovits J, Plow EF, Topol EJ. Platelet glycoprotein IIb/IIIa receptors in cardiovascular medicine. N Engl J Med. 1995;332:1553–9.CrossRefPubMedGoogle Scholar
  15. 15.
    Hanna EB, Rao SV, Manoukian SV, Saucedo JF. The evolving role of glycoprotein IIb/IIIa inhibitors in the setting of percutaneous coronary intervention strategies to minimize bleeding risk and optimize outcomes. JACC Cardiovasc Interv. 2010;3:1209–19.CrossRefPubMedGoogle Scholar
  16. 16.
    Mauri L, Kereiakes DJ, Yeh RW, et al. DAPT study Investigators. Twelve or 30 months of dual antiplatelet therapy after drug-eluting stents. N Engl J Med. 2014;371:2155–66.CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Levine GN, Bates ER, Bittl JA, et al. 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. 2016;68:1082–115.CrossRefPubMedGoogle Scholar
  18. 18.
    Yeh RW, Secemsky EA, Kereiakes DJ, et al. DAPT Study Investigators. Development and validation of a prediction rule for benefit and harm of dual antiplatelet therapy beyond 1 year after percutaneous coronary intervention. JAMA. 2016;315:1735–49.CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Bonaca MP, Bhatt DL, Cohen M, et al. PEGASUS-TIMI 54 Steering Committee and Investigators. Long-term use of ticagrelor in patients with prior myocardial infarction. N Engl J Med. 2015;372:1791–800.CrossRefPubMedGoogle Scholar
  20. 20.
    Montalescot G, White HD, Gallo R, et al. Enoxaparin vs. unfractionated heparin in elective percutaneous coronary intervention. N Engl J Med. 2006;355:1006–17.CrossRefPubMedGoogle Scholar
  21. 21.
    Collet J-P, Huber K, Cohen M, et al. A direct comparison of intravenous enoxaparin with unfractionated heparin in primary percutaneous coronary intervention (from the ATOLL trial). Am J Cardiol. 2013;112:1367–72.CrossRefPubMedGoogle Scholar
  22. 22.
    Kastrati A, Neumann FJ, Mehilli J, et al. Bivalirudin vs. unfractionated heparin during percutaneous coronary intervention. N Engl J Med. 2008;359:688–96.CrossRefPubMedGoogle Scholar
  23. 23.
    Schulz S, Mehilli J, Neumann FJ, et al. Intracoronary Stenting and Antithrombotic Regimen: Rapid Early Action for Coronary Treatment (ISAR-REACT) 3A Trial Investigators. ISAR-REACT 3A: a study of reduced dose of unfractionated heparin in biomarker negative patients undergoing percutaneous coronary intervention. Eur Heart J. 2010;31:2482–91.CrossRefPubMedGoogle Scholar
  24. 24.
    Stone GW, McLaurin BT, Cox DA, et al. Bivalirudin for patients with acute coronary syndromes. N Engl J Med. 2006;355:2203–16.CrossRefPubMedGoogle Scholar
  25. 25.
    Stone GW, White HD, Ohman EM, et al. Acute Catheterization and Urgent Intervention Triage strategy (ACUITY) Trial Investigators. Bivalirudin in patients with acute coronary syndromes undergoing percutaneous coronary intervention: a subgroup analysis from the Acute Catheterization and Urgent Intervention Triage strategy (ACUITY) trial. Lancet. 2007;369:907–19.CrossRefPubMedGoogle Scholar
  26. 26.
    Kastrati A, Neumann F-J, Schulz S, et al. Abciximab and heparin vs. bivalirudin for non-ST-elevation myocardial infarction. N Engl J Med. 2011;365:1980–9.CrossRefPubMedGoogle Scholar
  27. 27.
    Stone GW, Witzenbichler B, Guagliumi G, et al. HORIZONS-AMI Trial Investigators. Bivalirudin during primary PCI in acute myocardial infarction. N Engl J Med. 2008;358:2218–30.CrossRefPubMedGoogle Scholar
  28. 28.
    Steg PG, van ‘t Hof AW, Hamm CW, et al. Bivalirudin started during emergency transport for primary PCI. N Engl J Med. 2013;369:2207–17.CrossRefPubMedGoogle Scholar
  29. 29.
    Shahzad A, Kemp I, Mars C, et al. for the HEAT-PPCI trial investigators. Unfractionated heparin versus bivalirudin in primary percutaneous coronary intervention (HEAT-PPCI): an open-label, single centre, randomized controlled trial. Lancet. 2014;384:1848.CrossRefGoogle Scholar
  30. 30.
    Steg PG, Mehta SR, Pollack CV Jr, Investigators TAO. Anticoagulation with otamixaban and ischemic events in non-ST-segment elevation acute coronary syndromes: the TAO randomized clinical trial. JAMA. 2013;310:1145–55.CrossRefPubMedGoogle Scholar
  31. 31.
    Mega JL, Braunwald E, Wiviott SD, et al., the AACSTIRivaroxaban in patients with a recent acute coronary syndrome. N Engl J Med. 2012;366:9–19.CrossRefPubMedGoogle Scholar
  32. 32.
    Alexander JH, Lopes RD, James S, et al. Apixaban with antiplatelet therapy after acute coronary syndrome. N Engl J Med. 2011;365:699–708.CrossRefPubMedGoogle Scholar
  33. 33.
    Dewilde WJ, Oirbans T, Verheugt FW, et al. Use of clopidogrel with or without aspirin in patients taking oral anticoagulant therapy and undergoing percutaneous coronary intervention: an open label, randomised, controlled trial. Lancet. 2013;381:1107–15.CrossRefPubMedGoogle Scholar
  34. 34.
    Gibson CM, Mehran R, Bode C, et al. Prevention of bleeding in patients with atrial fibrillation undergoing PCI. N Engl J Med. 2016;375:2423–34.CrossRefPubMedGoogle Scholar
  35. 35.
    Ohman EM, Roe MT, Steg PG, et al. Clinically significant bleeding with low-dose rivaroxaban versus aspirin, in addition to P2Y12 inhibition, in acute coronary syndromes (GEMINI-ACS-1): a double-blind, multicentre, randomised trial. Lancet. 2017;389:1799–808.CrossRefPubMedGoogle Scholar
  36. 36.
    Gurbel PA, Tantry US. GEMINI-ACS-1: toward unearthing the antithrombotic therapy cornerstone for acute coronary syndromes. Lancet. 2017;89:1773–5.CrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Inova Center for Thrombosis Research and Drug DevelopmentInova Heart and Vascular InstituteFalls ChurchUSA

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