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. 2008 Mar 26;31(Suppl 1):I2–I9. doi: 10.1002/clc.20362

Antiplatelet Strategies: Evaluating Their Current Role in the Setting of Acute Coronary Syndromes

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: PMC6653726  PMID: 18481818

Abstract

Numerous clinical trials have established the value of antiplatelet therapies for acute coronary syndromes (ACS). Aspirin (ASA), thienopyridines (i.e., clopidogrel and ticlopidine) and GP IIb/IIIa antagonists comprise the major classes of antiplatelet therapies demonstrated to be of benefit in the treatment of ACS and for the prevention of thrombotic complications of percutaneous coronary intervention (PCI). Clopidogrel is beneficial when administered before and after PCI, and is more effective when combined with either ASA or GP IIb/IIIa inhibitors in preventing post‐PCI complications, coronary subacute stent thrombosis, and thrombotic events in general. It is currently unclear whether a higher loading dose of clopidogrel (600 mg) is better than the standard loading dose (300 mg), how long therapy should continue, and which maintenance dose is optimal. The role of the GP IIb/IIIa antagonists in ACS is less clear due to conflicting data from several studies with different patient populations. Currently, it appears that the use of GP IIb/IIIa antagonists might be most beneficial in high‐risk ACS patients scheduled to undergo PCI, who demonstrate non‐ST‐segment elevation myocardial infarction and elevated troponin levels. Copyright © 2008 Wiley Periodicals, Inc.

Keywords: catheterization/diagnostic interventional> cardiac, acute coronary syndromes> ischemic heart disease, platelets, thrombosis/hypercoagulable

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References

  • 1. Rosamond W, Flegal K, Friday G, Furie K, Greenlund K, for the American Heart Association Statistics Committee and Stroke Statistics Subcommittee : Heart disease and stroke statistics–2007 update: A report from the American heart association statistics committee and stroke statistics subcommittee. Circulation 2007; 115: e69–e171. [DOI] [PubMed] [Google Scholar]
  • 2. 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]
  • 3. Quinn MJ, Fitzgerald DJ. Ticlopidine and clopidogrel. Circulation 1999; 100: 1667–1672. [DOI] [PubMed] [Google Scholar]
  • 4. CAPRIE Steering Committee : A randomised, blinded, trial of clopidogrel versus aspirin in patients at risk of ischemic events (CAPRIE). Lancet 1996; 348: 1329–1339. [DOI] [PubMed] [Google Scholar]
  • 5. Yusuf S, Zhao F, Mehta SR, Chrolavicius S, Tognoni G, et al., for the Clopidogrel in Unstable Angina to Prevent Recurrent Ischemic Events (CURE) Trial Investigators : Effects of clopidogrel in addition to aspirin in patients with acute coronary syndromes without ST‐segment elevation. N Engl J Med 2001; 345: 494–502. [DOI] [PubMed] [Google Scholar]
  • 6. Mehta SR, Yusuf S, Peters RJ, Bertrand ME, Lewis BS, et al., for the CURE Investigators : 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. [DOI] [PubMed] [Google Scholar]
  • 7. Gurbel PA, Bliden KP, Hayes KM, Yoho JA, Herzog WR, 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. [DOI] [PubMed] [Google Scholar]
  • 8. Gurbel PA, Bliden KP, Zaman KA, Yoho JA, Hayes KM, et al.: Clopidogrel loading with eptifibatide to arrest the reactivity of platelets: results of teh Clopidogrel Loading With Eptifibatide to Arrest the Reactivity of Platelets (CLEAR PLATELETS) study. Circulation 2005; 111: 1153–1159. [DOI] [PubMed] [Google Scholar]
  • 9. von Beckerath N, Taubert D, Pogatsa‐Murray G, Shömig E, Kastrati A, et al.: Absorption, metabolization, and antiplatelet effects of 300‐, 600‐, and 900‐mg loading doses of clopidogrel: results of the ISAR‐CHOICE (Intracoronary Stenting and Antithrombotic Regimen: Choose Between 3 High Oral Doses for Immediate Clopidogrel Effect) Trial. Circulation 2005; 112: 2946–2950. [DOI] [PubMed] [Google Scholar]
  • 10. 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]
  • 11. 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: 2099–2016. [DOI] [PubMed] [Google Scholar]
  • 12. Steinhubl SR, Berger PB, Mann JT III, Fry ET, DeLago A, et al., for the CREDO Investigators : Clopidogrel for the Reduction of Events During Observation: Early and sustained dual oral antiplatelet therapy following percutaneous coronary intervention a randomized controlled trial. JAMA 2002; 288: 2411–2420. [DOI] [PubMed] [Google Scholar]
  • 13. Sabatine MS, Cannon CP, Gibson CM, López‐Sendón JL, Montalescot G, et al., for the CLARITY–TIMI 28 Investigators : Addition of Clopidogrel to aspirin and fibrinolytic therapy for myocardial infarction with ST‐Segment elevation. N Engl J Med 2005; 352: 1179–1189. [DOI] [PubMed] [Google Scholar]
  • 14. Sabatine MS, Cannon CP, Gibson CM, López‐Sendón JL, Montalescot G, et al., for the Clopidogrel as Adjunctive Reperfusion Therapy (CLARITY)‐Thrombolysis in Myocardial Infarction (TIMI) 28 Investigators : 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. [DOI] [PubMed] [Google Scholar]
  • 15. Chen ZM, Jiang LX, Chen YP, Xie JX, Pan HC, et al., for the ClOpidogrel and Metoprolol in Myocardial Infarction Trial (COMMIT) Collaborative Group : Addition of clopidogrel to aspirin in 45,852 patients with acute myocardial infarction: randomized placebo controlled trial. Lancet 2005; 366: 1607–1621. [DOI] [PubMed] [Google Scholar]
  • 16. Bhatt DL, Fox KAA, Hacke W, Berger PB, Black HR, et al., for the CHARISMA Investigators : Clopidogrel and aspirin versus aspirin alone for the prevention of atherothrombotic events. N Engl J Med 2006; 354: 1706–1717. [DOI] [PubMed] [Google Scholar]
  • 17. Bhatt DL, Flather MD, Hacke W, Berger PB, Black HR, et al.: Patients with prior myocardial infarction, stroke, or symptomatic peripheral arterial disease in the CHARISMA trial. J Am Coll Cardiol 2007; 49: 1982–1988. [DOI] [PubMed] [Google Scholar]
  • 18. Wang TH, Bhatt DL, Fox KA, Steinhuble SR, Brennan DM, et al.: An analysis of mortality rates with dual antiplatelet therapy in the primary prevention population of the CHARISMA trial. Eur Heart J 2007; 18: 2200–2207. [DOI] [PubMed] [Google Scholar]
  • 19. Steinhubl SR: Optimizing Antiplatelet therapy for the ACS patient: Reacting to clinical trial data from the ISAR‐REACT‐2 studies. Rev Cardiovasc Med 2006; 7: S12–S19. [PubMed] [Google Scholar]
  • 20. Boersma E, Harrington RA, Moliterno DJ, White H, Theroux P, et al.: Platelet glycoprotein IIb/IIIa inhibitors in acute coronary syndromes: a meta‐analysis of all major randomized clinical trials. Lancet 2002; 359: 189–198. [DOI] [PubMed] [Google Scholar]
  • 21. The Platelet Receptor Inhibition in Ischemic Syndrome Management (PRISM) Study Investigators : A comparison of aspirin plus tirofiban with aspirin plus heparin for unstable angina. N Engl J Med 1998; 338: 1498–1505. [DOI] [PubMed] [Google Scholar]
  • 22. PRISM‐PLUS Investigators : Inhibition of the platelet glycoprotein IIb/IIIa receptor with tirofiban in unstable angina and non‐Q‐wave myocardial infarction. Platelet Receptor Inhibition in Ischemic Syndrome Management in Patients Limited by Unstable Signs and Symptoms (PRISM‐PLUS) Study Investigators. N Engl J Med 1998; 338: 1488–1497. [DOI] [PubMed] [Google Scholar]
  • 23. CAPTURE Investigators : Randomised placebo‐controlled trial of abciximab before and during coronary intervention in refractory unstable angina: the CAPTURE study. Lancet 1997; 349: 1429–1435. [PubMed] [Google Scholar]
  • 24. Simoons ML for the GUSTO IV‐ACS Investigators . Effect of glycoprotein IIb/IIIa receptor blocker abciximab on outcome in patients with acute coronary syndromes without early coronary revascularization: the GUSTO IV‐ACS randomized trial. Lancet 2001; 357: 1915–1924. [DOI] [PubMed] [Google Scholar]
  • 25. Ottervanger JP, Armstrong P, Barnathan ES, Boersma E, Cooper JS for the GUSTO IV‐ACS Investigators : Long‐term results after the glycoprotein IIb/IIIa inhibitor abciximab in unstable angina: one‐year survival in the GUSTO IV‐ACS (Global Use of Strategies To Open Occluded Coronary Arteries IV–Acute Coronary Syndrome) Trial. Circulation 2003; 107: 437–442. [DOI] [PubMed] [Google Scholar]
  • 26. Topol EJ, Moliterno DJ, Herrmann HC, Powers ER, Grines CL, et al.: Comparison of two platelet glycoprotein IIb/IIIa inhibitors, tirofiban and abciximab, for the prevention of ischemic events with percutaneous coronary revascularization. N Engl J Med 2001; 344: 1888–1894. [DOI] [PubMed] [Google Scholar]
  • 27. Kastrati A, Mehilli J, Schühlen H, Dirschinger J, Dotzer F, et al.: A clinical trial of abciximab in elective percutaneous coronary intervention after pretreatment with clopidogrel. N Engl J Med 2004; 250: 232–238. [DOI] [PubMed] [Google Scholar]
  • 28. Kastrati A, Mehilli J, Neumann F‐J, Dotzer F, ten Berg J, et al., for the Intracoronary Stenting and Antithrombotic: Regimen Rapid Early Action for Coronary Treatment 2 (ISAR‐REACT 2) Trial Investigators : Abciximab in patients with acute coronary syndromes undergoing percutaneous coronary intervention after clopidogrel pretreatment: the ISAR‐REACT 2 randomized trial. JAMA 2006; 295: 1531–1538. [DOI] [PubMed] [Google Scholar]

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