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Optimal management of platelet function after coronary stenting

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Coronary stenting elicits vessel wall damage, and subsequent activation of platelets is implicated as a major component of complications such as acute, subacute, and late stent thrombosis. As such, dual antiplatelet therapy using aspirin and clopidogrel has become a routine adjunct to coronary stenting. Use of aspirin and clopidogrel with or without glycoprotein IIb/IIIa inhibitors after coronary stenting reduces the complication rate and improves long-term outcomes. Dual antiplatelet therapy using aspirin and clopidogrel is recommended for at least 4 weeks with bare metal stents, and for 3 to 6 months with drug-eluting stents for prevention of major adverse cardiac events. After coronary stenting, 1 year of dual antiplatelet therapy is recommended for prevention of future cardiac events. However, despite the use of antiplatelet agents, stent thrombosis occurs in approximately 1% of patients, with an increased likelihood of occurrence in high-risk patients or a lesion subset of patients. Although the incidence of stent thrombosis is low, stent thrombosis usually presents as acute coronary syndrome and the mortality rate is up to 45%. Thus, considering the widespread use of stents, a considerable number of people are inadequately protected from thrombotic events despite current standard antiplatelet therapy using aspirin and clopidogrel. A concern with clopidogrel is the loading time and loading dose required to achieve and maintain optimal inhibition of platelet aggregation. The current recommendation for ensuring maximum antiplatelet activity is administration of a 300-mg loading dose of clopidogrel initiated at least 6 hours prior to percutaneous coronary intervention (PCI), and ideally the day before. If this is not possible, a loading dose of 600 mg of clopidogrel should be administered at least 2 hours before PCI. Recently, new combinations of antiplatelet agents (ie, triple therapy using aspirin, clopidogrel, and cilostazol) and new drugs with potent antiplatelet effects (ie, Prasugrel [currently being developed by Sankyo Pharmaceuticals and Ube Pharmaceuticals in Japan and by Eli Lilly and Co. (Indianapolis, IN) in the United States], Cangrelor [currently being developed by AstraZeneca Pharmaceuticals, Wilmington, DE], and AZD6140) have been evaluated in clinical trials; such treatments may help reduce the number of cardiac events after coronary stenting.

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References and Recommended Reading

  1. Gawaz M, Neumann FJ, Ott I, et al.: Changes in membrane glycoproteins of circulating platelets after coronary stent implantation. Heart 1996, 76:166–172.

    Article  PubMed  CAS  Google Scholar 

  2. Inoue T, Sohma R, Miyazaki T, et al.: Comparison of activation process of platelets and neutrophils after coronary stent implantation versus balloon angioplasty for stable angina pectoris. Am J Cardiol 2000, 86:1057–1062.

    Article  PubMed  CAS  Google Scholar 

  3. Leon MB, Baim DS, Popma JJ, et al.: A clinical trial comparing three antithrombotic-drug regimens after coronary-artery stenting. Stent Anticoagulation Restenosis Study Investigators. N Engl J Med 1998, 339:1665–1671.

    Article  PubMed  CAS  Google Scholar 

  4. Cutlip DE, Baim DS, Ho KK, et al.: Stent thrombosis in the modern era: a pooled analysis of multicenter coronary stent clinical trials. Circulation 2001, 103:1967–1971.

    PubMed  CAS  Google Scholar 

  5. Karrillon GJ, Morice MC, Benveniste E, et al.: Intracoronary stent implantation without ultrasound guidance and with replacement of conventional anticoagulation by antiplatelet therapy: 30-day clinical outcome of the French Multicenter Registry. Circulation 1996, 94:1519–1527.

    PubMed  CAS  Google Scholar 

  6. Moussa I, Di Mario C, Reimers B, et al.: Subacute stent thrombosis in the era of intravascular ultrasound-guided coronary stenting without anticoagulation: frequency, predictors and clinical outcome. J Am Coll Cardiol 1997, 29:6–12.

    Article  PubMed  CAS  Google Scholar 

  7. Iskovou I, Schmidt T, Bonizzoni et al.: Incidence, predictors, and outcome of thrombosis after successful implantation of drug-eluting stents. JAMA 2005, 293:2126–2130.

    Article  Google Scholar 

  8. Antithrombotic Trialists’ Colloboration: Collaborative meta-analysis of randomised trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high risk patients. BMJ 2002, 324:71–86.

    Article  Google Scholar 

  9. Barnathan E, Schwartz J, Taylor L, et al.: Aspirin and dipyridamole in the prevention of acute coronary thrombosis complicating coronary angioplasty. Circulation 1987, 76:125–134.

    PubMed  CAS  Google Scholar 

  10. Schwartz L, Bourassa M, Lesperance J, et al.: Aspirin and dipyridamole in the prevention of restenosis after percutaneous transluminal coronary angioplasty. N Engl J Med 1988, 318:1714–1719.

    Article  PubMed  CAS  Google Scholar 

  11. Lembo NJ, Black AJ, Roubin GS, et al.: Effect of pretreatment with aspirin versus aspirin plus dipyridamole on frequency and type of acute complications of percutaneous transluminal coronary angioplasty. Am J Cardiol 1990, 65:422–426.

    Article  PubMed  CAS  Google Scholar 

  12. Bertrand ME, Legrand V, Boland J, et al.: Randomized multicenter comparison of conventional anticoagulation versus antiplatelet therapy in unplanned and elective coronary stenting: the full anticoagulation versus aspirin and ticlopidine (FANTASTIC) study. Circulation 1998, 98:1597–1603.

    PubMed  CAS  Google Scholar 

  13. Savcic M, Hauert J, Bachmann F, et al.: Clopidogrel loading dose regimens: kinetic profile of pharmacodynamic response in healthy subjects. Sem Thromb Hemost 1999, 25:15–19.

    CAS  Google Scholar 

  14. Schomig A, Neumann FJ, Kastrati A, et al.: A randomized comparison of antiplatelet and anticoagulant therapy after the placement of coronary-artery stents. N Engl J Med 1996, 334:1084–1089.

    Article  PubMed  CAS  Google Scholar 

  15. Muller C, Buttner H, Petersen J, et al.: A randomized comparison of clopidogrel and aspirin versus ticlopidine and aspirin after the placement of coronary-artery stents. Circulation 2000, 101:590–593.

    PubMed  CAS  Google Scholar 

  16. Moussa I, Oetgen M, Roubin G, et al.: Effectiveness of clopidogrel and aspirin versus ticlopidine and aspirin in preventing stent thrombosis after coronary stent implantation. Circulation 1999, 99:2364–2366.

    PubMed  CAS  Google Scholar 

  17. Mehta SR, Yusuf S, Peters RJ, et al.: Effects of pretreatment with clopidogrel and aspirin followed by long-term therapy in patients undergoing percutaneous coronary intervention: the PCI-CURE study. Lancet 2001, 358:527–533.

    Article  PubMed  CAS  Google Scholar 

  18. Steinhubl S, Berger P, Mann J, et al.: Early and sustained dual oral antiplatelet therapy following percutaneous coronary intervention: a randomized controlled trial. JAMA 2002, 288:2411–2420.

    Article  PubMed  CAS  Google Scholar 

  19. Sabatine MS, Cannon CP, Gibson CM, et al.: Effect of clopidogrel pretreatment before percutaneous coronary intervention in patients with ST-elevation myocardial infarction treated with fibrinolytics: the PCI-CLARITY study. JAMA 2005, 294:1224–1232.

    Article  PubMed  CAS  Google Scholar 

  20. Patti G, Colonna G, Pasceri V, et al.: Randomized trial of high loading dose of clopidogrel for reduction of periprocedural myocardial infarction in patients undergoing coronary intervention: results from the ARMYDA-2 (Antiplatelet therapy for Reduction of MYocardial Damage during Angioplasty) study. Circulation 2005, 111:2099–2106.

    Article  PubMed  CAS  Google Scholar 

  21. Kandzari DE, Berger PB, Kastrati A, et al.: Influence of treatment duration with a 600-mg dose of clopidogrel before percutaneous coronary revascularization. J Am Coll Cardiol 2004, 44:2133–2136.

    Article  PubMed  CAS  Google Scholar 

  22. Gurbel PA, Bliden KP, Hayes KM, et al.: The relation of dosing to clopidogrel responsiveness and the incidence of high post-treatment platelet aggregation in patients undergoing coronary stenting. J Am Coll Cardiol 2005, 45:1392–1396.

    Article  PubMed  CAS  Google Scholar 

  23. Gurbel PA, Bliden KP, Hiatt BL, et al.: Clopidogrel for coronary stenting: response variability, drug resistance, and the effect of pretreatment platelet reactivity. Circulation 2003, 107:2908–2913.

    Article  PubMed  Google Scholar 

  24. Gurbel PA, Bliden KP, Zaman KA, et al.: Clopidogrel loading with eptifibatide to arrest the reactivity of platelets: results of the Clopidogrel Loading With Eptifibatide to Arrest the Reactivity of Platelets (CLEAR PLATELETS) study. Circulation 2005, 111:1153–1159.

    Article  PubMed  CAS  Google Scholar 

  25. Gurbel PA, Cummings CC, Bell CR, et al.: Onset and extent of platelet inhibition by clopidogrel loading in patients undergoing elective coronary stenting: the Plavix Reduction Of New Thrombus Occurrence (PRONTO) trial. Am Heart J 2003, 145:239–247.

    Article  PubMed  CAS  Google Scholar 

  26. Gurbel PA, Samara WM, Bliden KP: Failure of clopidogrel to reduce platelet reactivity and activation following standard dosing in elective stenting: implications for thrombotic events and restenosis. Platelets 2004, 15:95–99.

    Article  PubMed  CAS  Google Scholar 

  27. Müller I, Seyfarth M, Rüdiger S, et al.: Effect of a high loading dose of clopidogrel on platelet function in patients undergoing coronary stent placement. Heart 2001, 85:92–93.

    Article  PubMed  Google Scholar 

  28. Park SW, Lee CW, Kim HS, et al.: Comparison of cilostazol versus ticlopidine therapy after stent implantation. Am J Cardiol 1999, 84:511–514.

    Article  PubMed  CAS  Google Scholar 

  29. Yoon Y, Shim WH, Lee DH, et al.: Usefulness of cilostazol versus ticlopidine in coronary artery stenting. Am J Cardiol 1999, 84:1375–1380.

    Article  PubMed  CAS  Google Scholar 

  30. Hashiguchi M, Ohno K, Nakazawa R, et al.: Comparison of cilostazol and ticlopidine for one-month effectiveness and safety after elective coronary stenting. Cardiovasc Drugs Ther 2004, 18:211–217.

    Article  PubMed  CAS  Google Scholar 

  31. Lee SW, Park SW, Hong MK, et al.: Comparison of cilostazol and clopidogrel after successful coronary stenting. Am J Cardiol 2005, 95:859–862.

    Article  PubMed  CAS  Google Scholar 

  32. Ahn JC, Song WH, Kwon JA, et al.: Effects of cilostazol on platelet activation in coronary stenting patients who already treated with aspirin and clopidogrel. Korean J Intern Med 2004, 19:230–236.

    PubMed  CAS  Google Scholar 

  33. Lee SW, Park SW, Hong MK, et al.: Triple versus dual antiplatelet therapy after coronary stenting: impact on stent thrombosis. J Am Coll Cardiol 2005, 46:1833–1837.

    Article  PubMed  CAS  Google Scholar 

  34. Inhibition of platelet glycoprotein IIb/IIIa with eptifibatide in patients with acute coronary syndromes. The PURSUIT Trial Investigators [no authors listed]. N Engl J Med 1998, 339:436–443.

  35. Inhibition of the platelet glycoprotein IIb/IIIa receptor with tirofiban in unstable angina and non-Q-wave myocardial infarction. PRISM-PLUS Study Investigators [no authors listed]. N Engl J Med 1998, 338:1488–1497.

  36. Bertrand ME, Simoons ML, Fox KA, et al.: Management of acute coronary syndromes in patients presenting without persistent ST-segment elevation. Eur Heart J 2002, 23:1809–1840.

    Article  PubMed  Google Scholar 

  37. Theroux P, Alexander J Jr, Dupuis J, et al.: Upstream use of tirofiban in patients admitted for an acute coronary syndrome in hospitals with or without facilities for invasive management. Am J Cardiol 2001, 87:375–380.

    Article  PubMed  CAS  Google Scholar 

  38. Greenbaum AB, Harrington RA, Hudson MP, et al.: Therapeutic value of eptifibatide at community hospitals transferring patients to tertiary referral centers early after admission for acute coronary syndromes. J Am Coll Cardiol 2001, 37:492–498.

    Article  PubMed  CAS  Google Scholar 

  39. Randomised placebo-controlled and balloon-angioplasty-controlled trial to assess safety of coronary stenting with use of platelet glycoprotein-IIb/IIIa blockade. The EPISTENT Investigators. Evaluation of Platelet IIb/IIIa Inhibitor for Stenting [no authors listed]. Lancet 1998, 352:87–92.

  40. Bolognese L, Falsini G, Liistro F, et al.: Randomized comparison of upstream tirofiban versus downstream high bolus dose tirofiban or abciximab on tissue-level perfusion and troponin release in high-risk acute coronary syndromes treated with percutaneous coronary interventions: the EVEREST trial. J Am Coll Cardiol 2006, 47:522–528.

    Article  PubMed  CAS  Google Scholar 

  41. Boden We, McKay RG: Optimal treatment of acute coronary syndromes—an evolving strategy. N Engl J Med 2001, 344:1939–1942.

    Article  PubMed  CAS  Google Scholar 

  42. Boden WE: “Routine invasive” versus “selective invasive” approaches to non-St-segment elevation acute coronary syndromes management in the post-stent/platelet inhibition era. J Am Coll Cardiol 2003, 41:113S–122S.

    Article  PubMed  Google Scholar 

  43. Gibson CM, Singh KP, Murphy SA, et al.: Braunwald E. Association between duration of tirofiban therapy before percutaneous intervention and tissue level perfusion (a TACTICS-TIMI 18 substudy). Am J Cardiol 2004, 94:492–494.

    Article  PubMed  CAS  Google Scholar 

  44. Lange RA, Hillis LD: Antiplatelet therapy for ischemic heart disease. N Engl J Med 2004, 350:277–280.

    Article  PubMed  CAS  Google Scholar 

  45. Petronio AS, Musumeci G, Limbruno U, et al.: Abciximab improves 6-month clinical outcome after rescue coronary angioplasty. Am Heart J 2002, 143:334–341.

    Article  PubMed  CAS  Google Scholar 

  46. Lev EI, Patel RT, Maresh KJ, et al.: Aspirin and clopidogrel drug response in patients undergoing percutaneous coronary intervention: the role of dual drug resistance. J Am Coll Cardiol 2006, 47:27–33.

    Article  PubMed  CAS  Google Scholar 

  47. Sugidachi A, Asai F, Ogawa T, et al.: The in vivo pharmacological profile of CS-747, a novel antiplatelet agent with platelet ADP receptor antagonist properties. Br J Pharmacol 2000, 129:1439–1446.

    Article  PubMed  CAS  Google Scholar 

  48. Niitsu Y, Jakubowski JA, Sugidachi A, et al.: Pharmacology of CS-747 (Prasugrel, LY640315), a novel, potent antiplatelet agent with in vivo P2Y12 receptor antagonist activity. Semin Thromb Hemost 2005, 31:184–194.

    Article  PubMed  CAS  Google Scholar 

  49. Jernberg T, Payne CD, Winters KJ, et al.: Prasugrel achieves greater inhibition of platelet aggregation and a lower rate of non-responders compared with clopidogrel in aspirin-treated patients with stable coronary artery disease. Eur Heart J 2006, 27:1166–1173.

    Article  PubMed  CAS  Google Scholar 

  50. Storey RF, Oldroyd KG, Wilcox RG: Open multicentre study of the P2T receptor antagonist AR-C69931MX assessing safety, tolerability and activity in patients with acute coronary syndromes. Thromb Haemost 2001, 85:401–407.

    PubMed  CAS  Google Scholar 

  51. Greenbaum AB, Grines CL, Bittl JA, et al.: Initial experience with an intravenous P2Y12 platelet receptor antagonist in patients undergoing percutaneous coronary intervention: results from a 2-part, phase II, multicenter, randomized, placebo-and active-controlled trial. Am Heart J 2006, 151:689.e1–689.e10.

    Article  CAS  Google Scholar 

  52. van Giezen JJJ, Humphries RG: Preclinical and clinical studies with selective reversible direct P2Y12 antagonists. Semin Thromb Hemost 2005, 31:195–204.

    Article  PubMed  Google Scholar 

  53. Husted S, Emanuelsson H, Heptinstall S, et al.: Pharmacodynamics, pharmacokinetics, and safety of the oral reversible P2Y12 antagonist AZD6140 with aspirin in patients with atherosclerosis: a double-blind comparison to clopidogrel with aspirin. Eur Heart J 2006, 27:1038–1047.

    Article  PubMed  CAS  Google Scholar 

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  1. Department of Internal Medicine, University of Ulsan College of Medicine, Asan Medical Center, 388-1 Poongnap-dong, Songpa-gu, Seoul, 138-736, Korea

    Seung-Jung Park

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Park, SJ., Lee, SW. Optimal management of platelet function after coronary stenting. Curr Treat Options Cardio Med 9, 37–45 (2007). https://doi.org/10.1007/s11936-007-0049-7

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