American Journal of Cardiovascular Drugs

, Volume 5, Issue 2, pp 93–102 | Cite as

Interventional Cardiovascular Pharmacotherapy

Current Issues
  • Abdallah G. Rebeiz
  • Joseph Adams
  • Robert A. Harrington
Current Opinion


In the last decade, a variety of novel anticoagulant and antiplatelet agents that improve outcomes in patients undergoing percutaneous coronary revascularization have emerged. During the next decade, continued refinements in catheter-based device technology should lead to further increases in the number of interventional procedures. The use of optimal antithrombotic strategies is pivotal in reducing adverse events among patients undergoing percutaneous coronary intervention (PCI). Our purpose is to review the current evidence regarding the efficacy of available adjunctive anticoagulant and antiplatelet agents in treating patients undergoing percutaneous coronary revascularization.

It should be borne in mind that patients undergoing PCI in the midst of an acute coronary event require a different level of coagulation and platelet aggregation inhibition than low-risk patients undergoing elective PCI for stable angina pectoris. Similarly, generalizing antithrombotic regimen safety data to a wide spectrum of catheter-based therapeutic devices should be avoided. A level of anticoagulation that is safe and effective for angioplasty and stent placement may not be sufficient for devices with longer intracoronary dwell times such as brachytherapy catheters. In light of current evidence, activated clotting times should be targeted in the 200- to 250-second range during elective PCI and in the 250- to 300-second range when intervening on a higher-risk lesion, such as one with an angiographically visible thrombus or in patients presenting with an acute coronary syndrome (ACS).

Low-dose enoxaparin sodium is an attractive antithrombin strategy in PCI because it is intrinsically adjusted for renal function, age, and concomitant glycoprotein (GP) IIb/IIIa antagonist use. Other low-molecular weight heparins have also been studied as adjunctive anticoagulants during cardiac catheterization. For example, in pilot studies, dalteparin sodium was shown to have a good safety profile when used alone or in combination with abciximab during PCI.

A wealth of data supports the use of a GP IIb/IIIa antagonist in patients presenting with ACS, especially those with high-risk features such as elevated cardiac markers; the systematic use of GP IIb/IIIa inhibitors in this population is therefore encouraged. Overall, the use of GP IIb/IIIa inhibitors reduces the incidence of thrombotic complications following PCI, is associated with a mortality benefit, but has no impact on the risk of restenosis.



We thank Dr Jennifer King of the Duke Clinical Research Institute for editorial assistance. No sources of funding were used to assist in the preparation of this article. The authors have no conflicts of interest that are directly relevant to the content of this article.


  1. 1.
    Gruntzig A. Transluminal dilatation of coronary-artery stenosis [letter]. Lancet 1978; I: 263CrossRefGoogle Scholar
  2. 2.
    American Heart Association. 1999 Heart and stroke statistical update. Dallas (TX): American Heart Association, 1998Google Scholar
  3. 3.
    American Heart Association. Heart disease and stroke statisics: 2004 update. Dallas (TX): American Heart Association, 2004Google Scholar
  4. 4.
    Young J, Kereiakes D, Grines C. Low-molecular-weight heparin therapy in percutaneous coronary intervention: the NICE 1 and NICE 4 trials. J Invasive Cardiol 2000; 12: E14–18PubMedGoogle Scholar
  5. 5.
    Montalescot G, Cohen M. Low molecular weight heparins in the cardiac catheterization laboratory. J Thromb Thrombolysis 1999; 7: 319–23PubMedCrossRefGoogle Scholar
  6. 6.
    Bittl J, Chaitman B, Feit F, et al. Bivalirudin versus heparin during coronary angioplasty for unstable or postinfarction angina: final report reanalysis of the Bivalirudin Angioplasty study. Am Heart J 2001; 142: 952–9PubMedCrossRefGoogle Scholar
  7. 7.
    Bivalirudin and provisional glycoprotein IIb/IIIa blockade compared with heparin and planned glycoprotein IIb/IIIa blockade during percutaneous coronary intervention: the REPLACE-2 investigators. JAMA 2003; 289: 853-63Google Scholar
  8. 8.
    Use of a monoclonal antibody directed against the platelet glycoprotein IIb/IIIa receptor in high-risk coronary angioplasty: the EPIC investigation. N Engl J Med 1994; 330: 956-61Google Scholar
  9. 9.
    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. Lancet 1998; 352: 87-92Google Scholar
  10. 10.
    ESPRIT Investigators. Novel dosing regimen of eptifibatide in planned coronary stent implantation (ESPRIT): a randomised, placebo-controlled trial: the ESPRIT investigators [published erratum appears in Lancet 2001; 357 (9265): 1370]. Lancet 2000; 356(9247): 2037–44.CrossRefGoogle Scholar
  11. 11.
    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: 2364–6PubMedCrossRefGoogle Scholar
  12. 12.
    Taniushi M, Kurz H, Lasala J. Randomized comparison of ticlopidine and clopidogrel after intracoronary stent implantation in a broad patient population. Circulation 2001; 104: 539–43CrossRefGoogle Scholar
  13. 13.
    Steinhubl S, Berger P, Mann J, et al. Early and sustained dual oral antiplatelet therapy following percutaneous coronary intervention. JAMA 2002; 288: 2411–20PubMedCrossRefGoogle Scholar
  14. 14.
    Herbert J, Petitou M, Lormeau J, et al. SR 90107A/Org31540, a novel anti-factor Xa antithrombotic agent. Cardiovasc Drug Rev 1997; 15: 1–26CrossRefGoogle Scholar
  15. 15.
    Vuillemenot A, Schiele F, Meneveau N, et al. Efficacy of a synthetic pentasaccharide, a pure factor Xa inhibitor, as an antithrombotic agent: a pilot study in the setting of coronary angioplasty. Thromb Haemost 1999; 81: 214–20PubMedGoogle Scholar
  16. 16.
    Dyke C, Becker R, Kleiman N, et al. First experience with direct factor Xa inhibition in patients with stable coronary disease: a pharmacokinetic and pharmacodynamic evaluation. Circulation 2002; 105: 2385–91PubMedCrossRefGoogle Scholar
  17. 17.
    Alexander J, Dyke C, Becker R, et al. Initial experience with a novel direct factor Xa inhibitor in percutaneous coronary intervention [abstract]. J Am Coll Cardiol 2002; 39 Suppl. A: 73ACrossRefGoogle Scholar
  18. 18.
    Hirsh J. Heparin. N Engl J Med 1991; 324: 1565–74PubMedCrossRefGoogle Scholar
  19. 19.
    Linhardt R, Gunay N. Production and chemical processing of low molecular weight heparins. Semin Thromb Hemost 1999; 25: 5–16PubMedCrossRefGoogle Scholar
  20. 20.
    Lindahl U, Thunberg L, Backstrom G, et al. Extension and structural variability of the antithrombin-binding sequence in heparin. J Biol Chem 1984; 259: 12368–76PubMedGoogle Scholar
  21. 21.
    Weitz J, Hudoba M, Massel D, et al. Clot-bound thrombin is protected from inhibition by heparin-antithrombin III but is susceptible to inactivation by antithrombin III-independent inhibitors. J Clin Invest 1990; 86: 385–91PubMedCrossRefGoogle Scholar
  22. 22.
    Teitel J, Rosenberg R. Protection of factor Xa from neutralization by the heparin-antithrombin complex. J Clin Invest 1983; 71: 1383–91PubMedCrossRefGoogle Scholar
  23. 23.
    Mascelli M, Kleiman N, Marciniak SJ, et al. Therapeutic heparin concentrations augment platelet reactivity: implications for the pharmacologic assessment of the glycoprotein IIb/IIIa antagonist abciximab. Am Heart J 2000; 139: 696–703PubMedCrossRefGoogle Scholar
  24. 24.
    Brieger D, Mak K, Kottke-Marchant K, et al. Heparin-induced thrombocytopenia. J Am Coll Cardiol 1998; 31: 1449–59PubMedCrossRefGoogle Scholar
  25. 25.
    Randomised placebo-controlled trial of abciximab before and during coronary intervention in refractory unstable angina: the CAPTURE study [published erratum appears in Lancet 1997; 350 (9079); 744]. Lancet 1997; 349 (9063): 1429-35Google Scholar
  26. 26.
    Fergusson J, Dougherty K, Gaos C, et al. Relation between procedural activated coagulation time and outcome after percutaneous transluminal coronary angioplasty. J Am Coll Cardiol 1994; 23: 1061–5CrossRefGoogle Scholar
  27. 27.
    Narins C, Hillegrass WJ, Nelson C, et al. Relation between activated clotting time during angioplasty and abrupt closure. Circulation 1996; 93: 667–71PubMedCrossRefGoogle Scholar
  28. 28.
    Chew D, Bhatt D, Lincoff A, et al. Defining the optimal activated clotting time during percutaneous coronary intervention. Circulation 2001; 103: 961–6PubMedCrossRefGoogle Scholar
  29. 29.
    Tolleson T, O’shea J, Bittl J, et al. Relationship between heparin anticoagulation and clinical outcomes in coronary stent implantation. J Am Coll Cardiol 2003; 41: 386–93PubMedCrossRefGoogle Scholar
  30. 30.
    Smith SJ, Dove J, Jacobs A, et al. ACC/AHA guidelines of percutaneous coronary interventions (revision of the 1993 PTCA guidelines): executive summary. A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (committee to revise the 1993 guidelines for percutaneous transluminal coronary angioplasty). J Am Coll Cardiol 2001; 37: 2215–38PubMedCrossRefGoogle Scholar
  31. 31.
    Pinto D, Lorenz D, Murphy S, et al. Association of an activated clotting time ≤250 seconds with adverse event rates after percutaneous coronary intervention using tirofiban and heparin. Am J Cardiol 2003; 91: 976–8PubMedCrossRefGoogle Scholar
  32. 32.
    Comparison of early invasive and conservative strategies in patients with unstable coronary syndromes treated with the glycoprotein IIb/IIIa inhibitor tirofiban: the TACTICS-TIMI 18 investigators. N Engl J Med 2001; 344: 1879-87Google Scholar
  33. 33.
    Koch K, Piek J, de Winter R, et al. Safety of low-dose heparin in elective coronary angioplasty. Heart 1997; 77: 517–22PubMedGoogle Scholar
  34. 34.
    Vainer J, Fleisch M, Gunnes P, et al. Low dose heparin for routine angioplasty and stenting. Am J Cardiol 1996; 78: 964–6PubMedCrossRefGoogle Scholar
  35. 35.
    Kaluski E, Krakover R, Cotter G, et al. Minimal heparinization in coronary angioplasty: how much heparin is really warranted? Am J Cardiol 2000; 85: 953–6PubMedCrossRefGoogle Scholar
  36. 36.
    Denardo S, Davis K, Reid P, et al. Efficacy and safety of minimal dose (< or = 1,000 units) unfractionated heparin with abciximab in percutaneous coronary intervention. Am J Cardiol 2003; 91: 1–5PubMedCrossRefGoogle Scholar
  37. 37.
    Denardo S, Davis K, Tcheng J. Adjunctive pharmacotherapy confined to an anti-platelet regimen during elective percutaneous coronary intervention. Circulation 2002; 106: II–517Google Scholar
  38. 38.
    Samama M, Bara L, Gerotziafas G. Mechanisms for the antithrombotic activity in man of low-molecular-weight heparins (LMWHs). Haemostasis 1994; 24: 105–17PubMedGoogle Scholar
  39. 39.
    Hirsh J, Levine M. Low molecular weight heparin. Blood 1992; 79: 1–17PubMedGoogle Scholar
  40. 40.
    Melandri G, Semprini F, Cervi V, et al. Comparison of efficacy of low molecular weight heparin (Parnaparin) with that of unfractionated heparin in the presence of activated platelets in healthy subjects. Am J Cardiol 1993; 72: 450–4PubMedCrossRefGoogle Scholar
  41. 41.
    Warkentin T, Levine M, Hirsh J, et al. Heparin-induced thrombocytopenia in patients treated with low-molecular-weight heparin or unfractionated heparin. N Engl J Med 1995; 332: 1330–5PubMedCrossRefGoogle Scholar
  42. 42.
    Enoxaparin prevents death and cardiac ischemic events in unstable angina/non-Q-wave myocardial infarction: results of the TIMI 11B trial. The TIMI 11B investigators. Circulation 1999; 100: 1593-601Google Scholar
  43. 43.
    Cohen M, Demers C, Gurfinkel E, et al. A comparison of low-molecular-weight heparin with unfractionated heparin for unstable coronary artery disease. N Engl J Med 1997; 337: 447–52PubMedCrossRefGoogle Scholar
  44. 44.
    Antman E, Cohen M, McCabe C, et al. Enoxaparin is superior to unfractionated heparin for preventing clinical events at 1-year follow-up of TIMI 11B and ESSENCE. Eur Heart J 2002; 23: 308–14PubMedCrossRefGoogle Scholar
  45. 45.
    Granger C. Strategies of patient care in acute coronary syndromes: rationale for the Global Registry of Acute Coronary Events (GRACE) registry. Am J Cardiol 2000; 86: 4–9CrossRefGoogle Scholar
  46. 46.
    Invasive compared with non-invasive treatment in unstable coronary artery disease: FRISC II prospective randomised multicentre study. The FRagmin and fast revascularization during Instability in Coronary artery disease (FRISC II) investigators. Lancet 1999; 354: 708-15Google Scholar
  47. 47.
    Fox K, Poole-Wilson P, Henderson R, et al. Interventional versus conservative treatment for patients with unstable angina or non-ST-elevation myocardial infarction: the British Heart Foundation RITA 3 randomised trial. Lancet 2002; 360: 743–51PubMedCrossRefGoogle Scholar
  48. 48.
    Collet J, Montalescot G, Lison L, et al. Percutaneous coronary intervention after subcutaneous enoxaparin pretreatment in patients with unstable angina pectoris. Circulation 2001; 103: 658–63PubMedCrossRefGoogle Scholar
  49. 49.
    Martin J, Fry E, Serano A, et al. Pharmacokinetic study of enoxaparin in patients undergoing coronary intervention after treatment with subcutaneous enoxaparin in acute coronary syndromes (ACS): the PEPCI study [abstract]. Eur Heart J 2001; 22: 143Google Scholar
  50. 50.
    Aslam M, Sundberg S, Sabri M, et al. Pharmacokinetics of intravenous/subcutaneous enoxaparin in patients with acute coronary syndrome undergoing percutaneous coronary interventions. Cathet Cardiovasc Interv 2002; 57: 187–90CrossRefGoogle Scholar
  51. 51.
    Kereiakes D, Montalescot G, Antman E, et al. Low-molecular-weight heparin therapy for non-ST-elevation acute coronary syndromes and during percutaneous coronary intervention: an expert consensus. Am Heart J 2002; 144: 615–24PubMedGoogle Scholar
  52. 52.
    Kereiakes D, Grines C, Fry E, et al. Enoxaparin and abciximab adjunctive pharmacotherapy during percutaneous coronary intervention. J Invasive Cardiol 2001; 13: 272–8PubMedGoogle Scholar
  53. 53.
    Choussat R, Montalescot G, Collet J, et al. A unique, low dose of intravenous enoxaparin in elective percutaneous coronary intervention. J Am Coll Cardiol 2002; 40: 1943–50PubMedCrossRefGoogle Scholar
  54. 54.
    Ferguson J, Antman E, Bates E, et al. The use of enoxaparin and IIb/IIIa antagonists in acute coronary syndromes, including PCI: final results of the NICE-3 study [abstract]. J Am Coll Cardiol 2001; 37: 365ACrossRefGoogle Scholar
  55. 55.
    Bhatt D, Lee B, Casterella P, et al. Safety of concomitant therapy with eptifibatide and enoxaparin in patients undergoing percutaneous coronary intervention. J Am Coll Cardiol 2003; 41: 20–5PubMedCrossRefGoogle Scholar
  56. 56.
    Natarajan M, Turpie G, Raco D, et al. A randomized comparison of dalteparin versus unfractionated heparin during percutaneous coronary interventions [abstract]. J Am Coll Cardiol 2003; 41: 68ACrossRefGoogle Scholar
  57. 57.
    Kereiakes D, Kleiman N, Fry E, et al. Dalteparin in combination with abciximab during percutaneous coronary intervention. Am Heart J 2001; 141: 348–52PubMedCrossRefGoogle Scholar
  58. 58.
    Marmur J, Anand S, Bagga R, et al. The activated clotting time can be used to monitor the low molecular weight heparin dalteparin after intravenous administration. J Am Coll Cardiol 2003; 41: 394–402PubMedCrossRefGoogle Scholar
  59. 59.
    Weitz J. Biologic rationale for the therapeutic role of specific antithrombins. Coron Artery Dis 1996; 7: 409–19PubMedCrossRefGoogle Scholar
  60. 60.
    Liaw P, Becker D, Stafford A, et al. Molecular basis for the susceptibility of fibrinbound thrombin inactivation by heparin cofactor II in the presence of dermatan sulfate but not heparin. J Biol Chem 2001; 276: 20959–65PubMedCrossRefGoogle Scholar
  61. 61.
    Maraganore J, Bourdon P, Jablonski J, et al. Design and characterization of Hirulogs: a novel class of bivalent peptide inhibitors of thrombin. Biochemistry 1990; 29: 7095–101PubMedCrossRefGoogle Scholar
  62. 62.
    Parry MA, Maraganore JM, Stone SR. Kinetic mechanism for the interaction of hirulog with thrombin. Biochemistry 1994; 33(49): 14807–14PubMedCrossRefGoogle Scholar
  63. 63.
    Weitz JI, Crowther M. Direct thrombin inhibitors. Thromb Res 2002; 106: V275-84Google Scholar
  64. 64.
    Topol E, Bonan R, Jewitt D, et al. Use of a direct antithrombin, hirulog, in place of heparin during coronary angioplasty. Circulation 1993; 87: 1622–9PubMedCrossRefGoogle Scholar
  65. 65.
    Heeschen C, Hamm C, Goldmann B, et al. Troponin concentrations for stratification of patients with acute coronary syndromes in relation to therapeutic efficacy of tirofiban. Lancet 1999; 354: 1757–62PubMedCrossRefGoogle Scholar
  66. 66.
    Newby L, Ohman E, Christenson R, et al. Benefit of glycoprotein IIb/IIIa inhibition in patients with acute coronary syndromes and troponin T-positive status: the PARAGON-B troponin T substudy. Circulation 2001; 103: 2891–6PubMedCrossRefGoogle Scholar
  67. 67.
    Lincoff A, Kleiman N, Kottke-Marchant K, et al. Bivalirudin with planned or provisional abciximab versus low-dose heparin and abciximab during percutaneous coronary revascularization: results of the Comparison of Abciximab Complications with Hirulog for Ischemic Events Trial (CACHET). Am Heart J 2002; 143: 847–53PubMedCrossRefGoogle Scholar
  68. 68.
    Cho L, Chew D, Moliterno D, et al. Safe and efficacious use of bivalirudin for percutaneous coronary intervention with adjunctive platelet glycoprotein IIb/ IIIa receptor inhibition. Am J Cardiol 2003; 91: 742–3PubMedCrossRefGoogle Scholar
  69. 69.
    Lincoff AM, Bittl JA, Kleiman NS, et al. Comparison of bivalirudin versus heparin during percutaneous coronary intervention: the Randomized Evaluation of PCI Linking Angiomax to reduced Clinical Events (REPLACE)-1 trial. Am J Cardiol 2004; 93: 1092–6PubMedCrossRefGoogle Scholar
  70. 70.
    Lewis B, Ferguson J, Grassman E, et al. Successful coronary interventions performed with argatroban anticoagulation in patients with heparin-induced thrombocytopenia and thrombosis syndrome. J Invasive Cardiol 1996; 8: 410–7PubMedGoogle Scholar
  71. 71.
    Treatment of proximal deep vein thrombosis with a novel synthetic compound (SR90107A/ORG31540) with pure anti-factor Xa activity: a phase II evaluation. The REMBRANDT investigators. Circulation 2000; 102: 2726-31Google Scholar
  72. 72.
    Moons A, Peters R, Bijsterveld N, et al. Recombinant nematode anticoagulant protein c2, an inhibitor of the tissue factor/factor VIIa complex, in patients undergoing elective coronary angioplasty. J Am Coll Cardiol 2003; 41: 2147–53PubMedCrossRefGoogle Scholar
  73. 73.
    Fuster V, Badimon L, Badimon J, et al. The pathogenesis of coronary artery disease and the acute coronary syndromes. N Engl J Med 1992; 326: 242–50PubMedCrossRefGoogle Scholar
  74. 74.
    Chesebro J, Fuster V. Thrombosis in unstable angina. N Engl J Med 1992; 327: 192–4PubMedCrossRefGoogle Scholar
  75. 75.
    Jordan R, Wagner C, Mascelli M, et al. Preclinical development of c7E3 Fab: a mouse/human chimeric monoclonal antibody fragment that inhibits platelet function by blockade of GP IIb/IIIa receptors with observations on the immunogenicity of c7E3 Fab in humans. In: Horton M, editor. Adhesion receptors as therapeutic targets. Boca Raton (FL): CRC Press, 1996: 281–305Google Scholar
  76. 76.
    Scarborough R, Rose J, Hsu M, et al. Barbourin: a GPIIb-IIIa-specific integrin antagonist from the venom of Sistrurus m. barbouri. J Biol Chem 1991; 266: 9359–62PubMedGoogle Scholar
  77. 77.
    Scarborough R, Naughton M, Teng W, et al. Design of potent and specific integrin antagonists with high specificity for glycoprotein IIb/IIIa. J Biol Chem 1993; 268: 1066–73PubMedGoogle Scholar
  78. 78.
    Phillips D, Teng W, Arfsten A, et al. Effects of Ca2+ on GP IIb-IIIa interactions with integrilin: enhanced GP IIb–IIIa binding and inhibition of platelet aggregation by reductions in the concentration of ionized calcium in plasma anticoagulated with citrate. Circulation 1997; 96: 1488–94PubMedCrossRefGoogle Scholar
  79. 79.
    Deckelbaum L, Sax F, Grossman W. Tirofiban, a nonpeptide inhibitor of the platelet glycoprotein IIb/IIIa receptor. In: Sasahara A, Loscalzo J, editors. New therapeutic agents in thrombosis and thrombolysis. New York: Marcel Dekker, 1997: 355–65Google Scholar
  80. 80.
    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. The PRISM-PLUS study investigators. N Engl J Med 1998; 338: 1488-97Google Scholar
  81. 81.
    Inhibition of platelet glycoprotein IIb/IIIa with eptifibatide in patients with acute coronary syndromes: the PURSUIT trial investigators. N Engl J Med 1998; 339: 436-43Google Scholar
  82. 82.
  83. 83.
    Efficacy and safety of tenecteplase in combination with enoxaparin, abciximab, or unfractionated heparin: the ASSENT-3 randomised trial in acute myocardial infarction. The ASSENT-3 investigators. Lancet 2001; 358: 605-13Google Scholar
  84. 84.
    Platelet glycoprotein IIb/IIIa receptor blockade and low-dose heparin during percutaneous coronary revascularization: the EPILOG investigators. N Engl J Med 1997; 336: 1689-96Google Scholar
  85. 85.
    Effects of platelet glycoprotein IIb/IIIa blockade with tirofiban on adverse cardiac events in patients with unstable angina or acute myocardial infarction undergoing coronary angioplasty: the RESTORE investigators. Circulation 1997; 96: 1445-53Google Scholar
  86. 86.
    Lincoff A, Tcheng J, Califf R, et al. Sustained suppression of ischemic complications of coronary intervention by platelet GP IIb/IIIa blockade with abciximab: one-year outcome in the EPILOG trial. Circulation 1999; 99: 1951–8PubMedCrossRefGoogle Scholar
  87. 87.
    Topol E, Mark D, Lincoff A, et al. Outcomes at 1 year and economic implications of platelet glycoprotein IIb/IIIa blockade in patients undergoing coronary stenting: results from a multicenter randomised trial. Lancet 1999; 354: 2019–24PubMedCrossRefGoogle Scholar
  88. 88.
    Topol E, Lincoff A, Kereiakes D, et al. Multi-year follow-up of abciximab therapy in three randomized, placebo-controlled trials of percutaneous coronary revascularization. Am J Med 2002; 113: 1–6PubMedCrossRefGoogle Scholar
  89. 89.
    Wohrle J, Grebe O, Nusser T, et al. Reduction of major adverse cardiac events with intracoronary compared with intravenous bolus application of abciximab in patients with acute myocardial infarction or unstable angina undergoing coronary angioplasty. Circulation 2003; 107: 1840–3PubMedCrossRefGoogle Scholar
  90. 90.
    Randomised placebo-controlled trial of effect of eptifibatide on complications of percutaneous coronary intervention: IMPACT-II. The IMPACT-II investigators. Lancet 1997; 349: 1422-8Google Scholar
  91. 91.
    Gold H, Gimple L, Yasuda T, et al. Pharmacodynamic study of F(ab)2 fragments of murine monoclonal antibody 7E3 directed against human platelet glycoprotein IIb/IIIa in patients with unstable angina pectoris. J Clin Invest 1990; 86: 651–9PubMedCrossRefGoogle Scholar
  92. 92.
    Tcheng J, Ellis S, George B, et al. Pharmacodynamics of chimeric glycoprotein IIb/ IIIa integrin antiplatelet antibody Fab 7E3 in high risk angioplasty. Circulation 1994; 90: 1757–64PubMedCrossRefGoogle Scholar
  93. 93.
    O’shea J, Buller C, Cantor W, et al. Long-term efficacy of platelet glycoprotein IIb/IIIa integrin blockade with eptifibatide in coronary stent intervention. JAMA 2002; 287: 618–21PubMedCrossRefGoogle Scholar
  94. 94.
    Topol E, Moliterno D, Herrmann H, 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: 1888–94PubMedCrossRefGoogle Scholar
  95. 95.
    Batchelor W, Tolleson T, Huang Y, et al. Randomized comparison of platelet inhibition with abciximab, tirofiban and eptifibatide during percutaneous coronary intervention in acute coronary syndromes. Circulation 2002; 106: 1470–6PubMedCrossRefGoogle Scholar
  96. 96.
    Karvouni E, Katritsis D, Ioannidis J. Intravenous glycoprotein IIb/IIIa receptor antagonists reduce mortality after percutaneous coronary intervention. J Am Coll Cardiol 2003; 41: 26–32PubMedCrossRefGoogle Scholar
  97. 97.
    Roffi M, Mukherjee D, Chew D, et al. Lack of benefit from intravenous platelet glycoprotein IIb/IIIa receptor inhibition as adjunctive treatment for percutaneous interventions of aortocoronary bypass grafts. Circulation 2002; 106: 3063–7PubMedCrossRefGoogle Scholar
  98. 98.
    Motwani J, Topol E. Aortocoronary saphenous vein graft disease: pathogenesis, predisposition, and prevention. Circulation 1998; 97: 916–31PubMedCrossRefGoogle Scholar
  99. 99.
    Baim D, Wahr D, George B, et al. Randomized trial of distal embolic protection device during percutaneous intervention of saphenous vein aorto-coronary bypass graft. Circulation 2002; 105: 1285–90PubMedCrossRefGoogle Scholar
  100. 100.
    Moses JW, Leon MB, Popma JJ, et al. Sirolimus-eluting stents versus standard stents in patients with stenosis in a native coronary artery: the SIRIUS investigators. N Engl J Med 2003; 349: 1315–23PubMedCrossRefGoogle Scholar
  101. 101.
    Geiger J, Brich J, Honig-Liedl P, et al. Specific impairment of human platelet P2Y (AC) ADP receptor-mediated signaling by the antiplatelet drug clopidogrel. Arterioscler Thromb Vasc Biol 1999; 19: 2007–11PubMedCrossRefGoogle Scholar
  102. 102.
    Schwartz U, Geiger J, Walter U, et al. Flow cytometry analysis of intracellular VASP phosphorylation for the assessment of activating and inhibitory signal transduction pathways in human platelets: definition and detection of ticlopidine/clopidogrel effects. Thromb Haemost 1999; 82: 1145–52Google Scholar
  103. 103.
    Schomig A, Neumann F, 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: 1084–9PubMedCrossRefGoogle Scholar
  104. 104.
    Leon M, Baim D, Popma J, et al. A clinical trial comparing three antithrombotic drug regimens after coronary artery stenting. N Engl J Med 1998; 339: 1665–71PubMedCrossRefGoogle Scholar
  105. 105.
    Gent M, Easton J, Hachinski V, et al. The Canadian American Ticlopidine Study (CATS) in thromboembolic stroke. Lancet 1989; I: 1215–20CrossRefGoogle Scholar
  106. 106.
    Bennet C, Kiss J, Weinberg P, et al. Thrombotic thrombocytopenic purpura after stenting and ticlopidine. Lancet 1998; 352: 1036–7CrossRefGoogle Scholar
  107. 107.
    Herbert J, Frehel D, Vallee E, et al. Clopidogrel, a novel antiplatelet and antithrombotic agent. Cardiovasc Drug Rev 1993; 11: 180–98CrossRefGoogle Scholar
  108. 108.
    Harker L, Marzec U, Kelly A, et al. Clopidogrel inhibition of stent, graft, and vascular thrombogenesis with antithrombotic enhancement by aspirin in nonhuman primates. Circulation 1998; 98: 2461–9PubMedCrossRefGoogle Scholar
  109. 109.
    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: 590–3PubMedCrossRefGoogle Scholar
  110. 110.
    Bertrand M, Rupprecht H, Urban P, et al. Double-blind study of the safety of clopidogrel with and without a loading dose in combination with aspirin compared with ticlopidine in combination with aspirin after coronary stenting: the clopidogrel aspirin stent international cooperative study (CLASSICS). Circulation 2000; 102: 624–9PubMedCrossRefGoogle Scholar
  111. 111.
    Effects of clopidogrel in addition to aspirin in patients with acute coronary syndromes without ST-segment elevation: the CURE trial investigators. N Engl J Med 2001; 345: 494-502Google Scholar
  112. 112.
    Stone GW, Ellis SG, Cox DA, et al. A polymer-based, paclitaxel-eluting stent in patients with coronary artery disease: the TAXUS-IV investigators. N Engl J Med 2004; 350: 221–31PubMedCrossRefGoogle Scholar
  113. 113.
    Seyfarth HJ, Koksch M, Roethig G, et al. Effect of 300- and 450mg clopidogrel loading doses on membrane and soluble P-selectin in patients undergoing coronary stent implantation. Am Heart J 2002; 143: 118–23PubMedCrossRefGoogle Scholar
  114. 114.
    Muller I, Seyfarth M, Rudiger S, et al. Effect of a high loading dose of clopidogrel on platelet function in patients undergoing coronary stent placement. Heart 2001; 85: 92–3PubMedCrossRefGoogle Scholar
  115. 115.
    Helft G, Osende J, Worthley S, et al. Acute antithrombotic effect of front-loaded regimen of clopidogrel in patients with atherosclerosis on aspirin. Arterioscler Thromb Vasc Biol 2000; 20: 2316–21PubMedCrossRefGoogle Scholar
  116. 116.
    Kastrati A, Mehilli J, Schühlen H, et al. A clinical trial of abciximab in elective percutaneous coronary intervention after pretreatment with clopidogrel: the Intracoronary Stenting and Antithrombotic Regimen-Rapid Early Action for Coronary Treatment (ISAR-REACT) study investigators. N Engl J Med 2004; 350: 232–8PubMedCrossRefGoogle Scholar

Copyright information

© Adis Data Information BV 2005

Authors and Affiliations

  • Abdallah G. Rebeiz
    • 1
  • Joseph Adams
    • 1
  • Robert A. Harrington
    • 1
  1. 1.Division of Cardiology and Duke Clinical Research InstituteDuke University Medical CenterDurhamUSA

Personalised recommendations