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. 2008 Mar 26;31(Suppl 1):I28–I35. doi: 10.1002/clc.20359

Clinical Considerations with the Use of Antiplatelet Therapy in Patients Undergoing Percutaneous Coronary Intervention

Eugene Braunwald 1,✉, Dominick Angiolillo 2, Eric Bates 3, Peter B Berger 4, Deepak Bhatt 5, Christopher P Cannon 1, Mark I Furman 6, Paul Gurbel 7, Alan D Michelson 8, Eric Peterson 9, Stephen Wiviott 1
PMCID: PMC6652829  PMID: 18481820

Abstract

Despite the proven benefits of using antiplatelet therapy in patients undergoing percutaneous coronary intervention (PCI), a number of key questions remain to be answered. In recent years, clopidogrel dosing strategies among such patients have evolved considerably, with newer approaches involving loading doses prior to PCI and increases in the time interval and loading dosage in an effort to overcome variable responsiveness/hyporesponsiveness to platelet inhibition. Further, the role of glycoprotein (GP) IIb/IIIa antagonists in elective stenting continues to be defined, with recent evidence suggesting that most appropriate use of these agents is in high‐risk patients with elevated troponin levels. There appears to be a relationship between the use of GP IIb/IIIa antagonists with clopidogrel loading and attenuation of early inflammatory and cardiac marker release. Strategies to minimize the chance of late stent thrombosis in patients who receive drug‐eluting stents (DES) are also under intense investigation. Among some patients receiving sirolimus and paclitaxel DES, current standard long‐term antiplatelet strategies may be insufficient. Patient nonadherence to treatment and premature discontinuation and underutilization of antiplatelet therapies by physicians remain important clinical problems with potentially dire consequences. Copyright © 2008 Wiley Periodicals, Inc.

Keywords: catheterization/diagnostic interventional <cardiac, platelets, thrombosis/hypercoagulable states, acute coronary syndromes <ischemic heart disease, myocardial infarction <ischemic heart disease

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References

  • 1. Gurbel PA, Bliden KP, Hiatt BL, O'Connor CM: Clopidogrel for coronary stenting: response variability, drug resistance, and the effect of pretreatment platelet reactivity. Circulation 2003; 107 2908–2913. [DOI] [PubMed] [Google Scholar]
  • 2. Serebruany VL, Steinhubl SR, Berger PB, Malinin AI, Bhatt DL, et al.: Variability in platelet responsiveness to clopidogrel among 544 individuals. J Am Coll Cardiol 2005; 45: 246–251. [DOI] [PubMed] [Google Scholar]
  • 3. Steinhubl SR, Berger LPB, Mann JT III, Fry ETA, DeLago A, et al.: Early and sustained dual oral antiplatelet therapy following percutaneous coronary intervention. A randomized controlled trial. JAMA 2002; 288: 2411–2420. [DOI] [PubMed] [Google Scholar]
  • 4. Patti G, Colonna G, Pasceri V, Pepe LL, Montinaro A, 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. [DOI] [PubMed] [Google Scholar]
  • 5. Montalescot G, Sideris G, Meuleman C, Bal‐dit‐Sollier C, Lellouche N, et al.: A randomized comparison of high clopidogrel loading doses in patients with non–ST‐segment elevation acute coronary syndromes: the ALBION (Assessment of the Best Loading Dose of Clopidogrel to Blunt Platelet Activation, Inflammation and Ongoing Necrosis) trial. J Am Coll Cardiol 2006; 48: 931–938. [DOI] [PubMed] [Google Scholar]
  • 6. Kastrati A, von Beckerath N, Joost A, Pogatsa‐Murray G, Gorchakova O, et al.: Loading with 600 mg clopidogrel in patients with coronary artery disease with and without chronic clopidogrel therapy. Circulation 2004; 110: 1916–1919. [DOI] [PubMed] [Google Scholar]
  • 7. von Beckerath N, Kastrati A, Wieczorek A, Pogatsa‐Murray G, Sibbing D, et al.: A double‐blind, randomized study on platelet aggregation in patients treated with a daily dose of 150 or 75 mg of clopidogrel for 30 days. Eur Heart J 2007; 28: 1814–1819. [DOI] [PubMed] [Google Scholar]
  • 8. Ferreira IA, Mocking AIM, Feijge MAH, Gorter G, van Haeften TW, et al.: Platelet inhibition by insulin is absent in type 2 diabetes mellitus. Arterioscler Thromb Vasc Biol 2006; 26: 417–422. [DOI] [PubMed] [Google Scholar]
  • 9. Ferroni P, Basili S, Falco A, Davi G: Platelet activation in type 2 diabetes mellitus. J Thromb Haemost 2004; 1: 1282–1291. [DOI] [PubMed] [Google Scholar]
  • 10. Angiolillo DJ, Fernandez‐Ortiz A, Bernardo E, Ramirez C, Sabate M, et al.: Platelet function profiles in patients with type 2 diabetes and coronary artery disease on combined aspirin and clopidogrel treatment. Diabetes 2005; 54: 2430–2435. [DOI] [PubMed] [Google Scholar]
  • 11. Angiolillo DJ, Shoemaker SB, Desai B, Yuan H, Charlton RK, et al.: Randomized comparison of high clopidogrel maintenance dose in patients with diabetes mellitus and coronary artery disease: results of the Optimizing Antiplatelet Therapy in Diabetes Mellitus (OPTIMUS) study. Circulation 2007; 115: 708–716. [DOI] [PubMed] [Google Scholar]
  • 12. Bhatt DL, Fox KA, Hacke W, Berger PB, Black HR, et al.: Clopidogrel and aspirin versus aspirin alone for the prevention of atherothrombotic events. N Engl J Med 2006; 354: 1706–1717. [DOI] [PubMed] [Google Scholar]
  • 13. Mehta SR: Clopidogrel in non–ST segment elevation acute coronary syndromes. Eur Heart J 2006; 8: G25–G30. [Google Scholar]
  • 14. Steinhubl SR, Berger PB, Brennan DM, Topol EJ, For the CREDO investigators: Optimal timing for the initiation of pre‐treatment with 300 mg clopidogrel before percutaneous coronary intervention. J Am Coll Cardiol 2006; 47: 939–943. [DOI] [PubMed] [Google Scholar]
  • 15. Kandzari DE, Berger PB, Kastrati A, Steinhubl SR, Mehilli J, 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. [DOI] [PubMed] [Google Scholar]
  • 16. Anderson JL, Adams CD, Antman EM, Bridges CR, Califf RM, for the American College of Cardiology/American Heart Association Writing Committee to Revise the 2002 Guidelines for the Management of Patients with Unstable Angina/Non‐ST‐Elevation Myocardial Infarction. A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol 2007; 50: e1–e157. [DOI] [PubMed] [Google Scholar]
  • 17. Gurbel PA, Bliden KP, Zaman KA, Yoho JA, Hayes KM, et al.: Clopidogrel loading with eptifibatide to arrest the reactiviety of platelets: results of the clopidogrel loading with eptifibatide to arrest the reactivity of platelets (CLEAR PLATELETS) study. Circulation 2005; 111: 1153–1159. [DOI] [PubMed] [Google Scholar]
  • 18. Gurbel PA, Bliden KP, Tantry US: Effect of clopidogrel with and without eptifibatide on tumor necrosis factor‐alpha and C‐reactive protein release after elective stenting: results from the CLEAR PLATELETS 1b study. J Am Coll Cardiol 2006; 48: 2186–2191. [DOI] [PubMed] [Google Scholar]
  • 19. Bavry AA, Kumbhani DJ, Helton TJ, Borek PP, Mood GR, et al.: Late thrombosis of drug‐eluting stents: a meta‐analysis of randomized clinical trials. Am J Med 2006; 119: 1056–1061. [DOI] [PubMed] [Google Scholar]
  • 20. Pfisterer M, Brunner‐La Rocca HP, Buser PT, Rickenbacher P, Hunziker P, et al.: Late clinical events after clopidogrel discontinuation may limit the benefit of drug‐eluting stents: an observational study of drug‐eluting versus bare‐metal stents. J Am Coll Cardiol 2006; 48: 2584–2591. [DOI] [PubMed] [Google Scholar]
  • 21. Eisenstein EL, Anstrom KJ, Kong DF, Shaw LK, Tuttle RH, et al.: Clopidogrel use and long‐term clinical outcomes after drug‐eluting stent implantation. JAMA 2007; 297: 159–168. [DOI] [PubMed] [Google Scholar]
  • 22. Bhatt DL, Steg PG, Ohman EM, Hirsch AT, Ikeda Y, et al.: International prevalence, recognition, and treatment of cardiovascular risk factors in outpatients with atherothrombosis. JAMA 2006; 295: 180–189. [DOI] [PubMed] [Google Scholar]
  • 23. Smith SC Jr, Feldman TE, Hirshfeld JW Jr, Jacobs AK, Kern MJ, et al.: ACC/AHA/SCAI 2005 guideline update for percutaneous coronary intervention: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (ACC/AHA/SCAI Writing Committee to Update 2001 Guidelines for Percutaneous Coronary Intervention). Circulation 2006; 113(7): e166–e286. [DOI] [PubMed] [Google Scholar]
  • 24. Iakovou I, Schmidt T, Bonizzoni E, Ge L, Sangiori JM, et al.: Incidence, predictors, and outcome of thrombosis after successful implantation of drug‐eluting stents. JAMA 2005; 293: 2126–2130. [DOI] [PubMed] [Google Scholar]
  • 25. Park DW, Park SW, Park KH, Lee BK, Kim YH, et al.: Frequency of and risk factors for stent thrombosis after drug‐eluting stent implantation during long‐term follow‐up. Am J Cardiol 2006; 98: 352–256. [DOI] [PubMed] [Google Scholar]
  • 26. Jeremias A, Sylvia B, Bridges J, Kirtane AJ, Bigelow B, et al.: Stent thrombosis after successful sirolimus‐eluting stent implantation. Circulation 2004; 109: 1930–1932. [DOI] [PubMed] [Google Scholar]
  • 27. Spertus JA, Kettelkamp R, Vance C, Decker C, Jones PG, et al.: Prevalence, predictors, and outcomes of premature discontinuation of thienopyridine therapy after drug‐eluting stent placement: results from the PREMIER registry. Circulation 2006; 113: 2803–2809. [DOI] [PubMed] [Google Scholar]
  • 28. Grines CL, Bonow RO, Casey DE Jr, Gardner TJ, Lockhart PB, et al.: Prevention of premature discontinuation of dual antiplatelet therapy in patients with coronary artery stents. A science advisory from the American Heart Association, American College of Cardiology, Society for Cardiovascular Angiography and Interventions, American College of Surgeons, and American Dental Association, with representation from the American College of Physicians. Circulation 2007; 115: 813–818. [DOI] [PubMed] [Google Scholar]
  • 29. Curfman GD, Morrissey S, Jarcho JA, Drazen JM: Drug‐eluting coronary stents—promise and uncertainty. N Engl J Med 2007; 356: 1059–1060. [DOI] [PubMed] [Google Scholar]

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