, Volume 62, Issue 18, pp 2589–2601 | Cite as

A Guide to Drug Use During Percutaneous Coronary Intervention

  • Joseph K. Choo
  • John J. Young
  • Dean J. Kereiakes
Therapy In Practice


The past decade has seen major advances in adjunctive pharmacotherapy for percutaneous coronary intervention. Pharmacological therapeutic advances have resulted from a greater understanding of the pathophysiological mechanisms underlying platelet activation and aggregation, thrombin generation and thrombus formation. Specifically, refinements in the use of unfractionated heparin, developments in the use of low molecular weight heparins and direct antithrombin agents as well as improvement in both oral and parenteral adjunctive antiplatelet therapies have occurred and are reviewed herein.



The authors have received funding for clinical research trials from Aventis, Pharmacia & Upjohn, Eli Lilly and Company, Centocor, Merck, Cor Therapeutics and The Medicines Company. The authors declare no conflict of interest.


  1. 1.
    de Feyter PJ, van den Brand M, Laarman GJ, et al. Acute coronary artery occlusion during and after percutaneous transluminal coronary angioplasty. Frequency, prediction, clinical course, management, and follow-up. Circulation 1991; 83: 927–36Google Scholar
  2. 2.
    Lincoff AM, Popma JJ, Ellis SG, et al. Abrupt vessel closure complicating coronary angioplasty: clinical, angiographic and therapeutic profile. J Am Coll Cardiol 1992; 19: 926–35PubMedCrossRefGoogle Scholar
  3. 3.
    Detre KM, Holmes Jr DR, Holubkov R, et al. Incidence and consequences of periprocedural occlusion. The 1985–1986 National Heart, Lung, and Blood Institute Percutaneous Transluminal Coronary Angioplasty Registry. Circulation 1990; 82: 739–50Google Scholar
  4. 4.
    Uchida Y, Hasegawa K, Kawamura K, et al. Angioscopic observation of the coronary luminal changes induced by percutaneous transluminal coronary angioplasty. Am Heart J 1989; 117: 769–76PubMedCrossRefGoogle Scholar
  5. 5.
    Waller BF, Gorfinkel HJ, Rogers FJ, et al. Early and late morphologic changes in major epicardial coronary arteries after percutaneous transluminal coronary angioplasty. Am J Cardiol 1984; 53: C42–7CrossRefGoogle Scholar
  6. 6.
    Waller BF, Pinkerton CA, Orr CM, et al. Morphological observations late (greater than 30 days) after clinically successful coronary balloon angioplasty. Circulation 1991; 83: I28–41PubMedGoogle Scholar
  7. 7.
    Ferguson III JJ. Conventional antithrombotic approaches. Am Heart J 1995; 130: 651–7PubMedCrossRefGoogle Scholar
  8. 8.
    Wilcox JN, Smith KM, Schwartz SM, et al. Localization of tissue factor in the normal vessel wall and in the atherosclerotic plaque. Proc Natl Acad Sci U S A 1989; 86: 2839–43PubMedCrossRefGoogle Scholar
  9. 9.
    Rund MM, Smith DD, DeLuca SA, coordinators/investigators. Heparin during coronary angioplasty: are there any rules?. Circulation 1994: I-487Google Scholar
  10. 10.
    McGarry Jr TF, Gottlieb RS, Morganroth J, et al. The relationship of anticoagulation level and complications after successful percutaneous transluminal coronary angioplasty. Am Heart J 1992; 123: 1445–51PubMedCrossRefGoogle Scholar
  11. 11.
    Frierson JH, Dimas AP, Simpfendorfer CC, et al. Is aggressive heparinization necessary for elective PTCA? Cathet Cardiovasc Diagn 1993; 28: 279–82PubMedCrossRefGoogle Scholar
  12. 12.
    Hirsh J. Heparin. N Engl J Med 1991; 324: 1565–74PubMedCrossRefGoogle Scholar
  13. 13.
    Theroux P, Waters D, Lam J, et al. Reactivation of unstable angina after the discontinuation of heparin. N Engl J Med 1992; 327: 141–5PubMedCrossRefGoogle Scholar
  14. 14.
    Bull MH, Huse WM, Bull BS. Evaluation of tests used to monitor heparin therapy during extracorporeal circulation. Anesthesiology 1975; 43: 346–53PubMedCrossRefGoogle Scholar
  15. 15.
    Vaitkus PT, Herrmann HC, Laskey WK. Management and immediate outcome of patients with intracoronary thrombus during percutaneous transluminal coronary angioplasty. Am Heart J 1992; 124: 1–8PubMedCrossRefGoogle Scholar
  16. 16.
    Ferguson JJ, Dougherty KG, Gaos CM, et al. Relation between procedural activated coagulation time and outcome after percutaneous transluminal coronary angioplasty. J Am Coll Cardiol 1994; 23: 1061–5PubMedCrossRefGoogle Scholar
  17. 17.
    Narins CR, Hillegass Jr WB, Nelson CL, et al. Relation between activated clotting time during angioplasty and abrupt closure. Circulation 1996; 93: 667–71PubMedCrossRefGoogle Scholar
  18. 18.
    Laskey MA, Deutsch E, Barnathan E, et al. Influence of heparin therapy on percutaneous transluminal coronary angioplasty outcome in unstable angina pectoris. Am J Cardiol 1990; 65: 1425–9PubMedCrossRefGoogle Scholar
  19. 19.
    Laskey MA, Deutsch E, Hirshfeld Jr JW, et al. Influence of heparin therapy on percutaneous transluminal coronary angioplasty outcome in patients with coronary arterial thrombus. Am J Cardiol 1990; 65: 179–82PubMedCrossRefGoogle Scholar
  20. 20.
    Satler LF, Leon MB, Kent KM, et al. Strategies for acute occlusion after coronary angioplasty. J Am Coll Cardiol 1992; 19: 936–8PubMedCrossRefGoogle Scholar
  21. 21.
    Smith Jr SC, Dove JT, Jacobs AK, 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: 2215–38PubMedGoogle Scholar
  22. 22.
    Hillegass WB, Narins CR, Brott BC, et al. Activated clotting time predicts bleeding complications from angioplasty [abstract]. J Am Coll Cardiol 1994; 23: 184ACrossRefGoogle Scholar
  23. 23.
    Chew DP, Bhatt DL, Lincoff AM, et al. Defining the optimal activated clotting time during percutaneous coronary intervention: aggregate results from 6 randomized, controlled trials. Circulation 2001; 103: 961–6PubMedCrossRefGoogle Scholar
  24. 24.
    Boccara A, Benamer H, Juliard JM, et al. A randomized trial of a fixed high dose vs a weight-adjusted low dose of intravenous heparin during coronary angioplasty. Eur Heart J 1997; 18: 631–5PubMedCrossRefGoogle Scholar
  25. 25.
    Koch KT, Piek JJ, de Winter RJ, et al. Safety of low dose heparin in elective coronary angioplasty. Heart 1997; 77: 517–22PubMedGoogle Scholar
  26. 26.
    Vainer J, Fleisch M, Gunnes P, et al. Low-dose heparin for routine coronary angioplasty and stenting. Am J Cardiol 1996; 78: 964–6PubMedCrossRefGoogle Scholar
  27. 27.
    Moliterno DJ, Califf RM, Aguirre FV, et al. Effect of platelet glycoprotein IIb/IIIa integrin blockade on activated clotting time during percutaneous transluminal coronary angioplasty or directional atherectomy (the EPIC trial). Evaluation of c7E3 Fab in the Prevention of Ischemic Complications trial. Am J Cardiol 1995; 75: 559–62Google Scholar
  28. 28.
    Ammar T, Scudder LE, Coller BS. In vitro effects of the platelet glycoprotein IIb/IIIa receptor antagonist c7E3 Fab on the activated clotting time. Circulation 1997; 95: 614–7PubMedCrossRefGoogle Scholar
  29. 29.
    EPIC investigators. Use of a monoclonal antibody directed against the platelet glycoprotein IIb/IIIa receptor in high-risk coronary angioplasty. N Engl J Med 1994; 330: 956–61CrossRefGoogle Scholar
  30. 30.
    EPILOG Investigators. Platelet glycoprotein IIb/IIIa receptor blockade and low-dose heparin during percutaneous coronary revascularization. N Engl J Med 1997; 336: 1689–96CrossRefGoogle Scholar
  31. 31.
    Breddin HK. Coronary heart disease, unstable angina, PTCA: new indications for low molecular weight heparins? Thromb Res 1996; 81: S47–51PubMedCrossRefGoogle Scholar
  32. 32.
    Turpie AG. Successors to heparin: new antithrombotic agents. Am Heart J 1997; 134: S71–7PubMedCrossRefGoogle Scholar
  33. 33.
    Cohen M, Demers C, Gurfinkel EP, et al. A comparison of low-molecular-weight heparin with unfractionated heparin for unstable coronary artery disease. Efficacy and Safety of Subcutaneous Enoxaparin in Non-Q-Wave Coronary Events Study Group. N Engl J Med 1997; 337: 447–52Google Scholar
  34. 34.
    Antman EM. TIMI 11B. Enoxaparin versus unfractionated heparin for unstable angina or non-Q-wave myocardial infarction: a double-blind, placebo-controlled, parallel-group, multicenter trial. Rationale, study design, and methods. Thrombolysis in Myocardial Infarction (TIMI) 11B Trial Investigators. Am Heart J 1998; 135: S353–60PubMedCrossRefGoogle Scholar
  35. 35.
    Antman EM, Cohen M. Newer antithrombin agents in acute coronary syndromes. Am Heart J 1999; 138: S563–9PubMedCrossRefGoogle Scholar
  36. 36.
    Antman EM, Kereiakes DJ. Antithrombotic therapy in unstable angina/non-ST elevation myocardial infarction: the evolving role of low-molecular-weight heparin. J Invasive Cardiol 2000; 12 Suppl E: E1–4; discussion E25-8PubMedGoogle Scholar
  37. 37.
    Kereiakes DJ, Fry E, Matthai W, et al. Combination enoxaparin and abciximab therapy during percutaneous coronary intervention: “NICE guys finish first”. J Invasive Cardiol 2000; 12 Suppl. A: 1A–5APubMedGoogle Scholar
  38. 38.
    Karsch KR, Preisack MB, Baildon R, et al. Low molecular weight heparin (reviparin) in percutaneous transluminal coronary angioplasty. Results of a randomized, double-blind, unfractionated heparin and placebo-controlled, multicenter trial (REDUCE trial). Reduction of Restenosis After PTCA, Early Administration of Reviparin in a Double-Blind Unfractionated Heparin and Placebo-Controlled Evaluation. J Am Coll Cardiol 1996; 28: 1437–43Google Scholar
  39. 39.
    Rabah MM, Premmereur J, Graham M, et al. Usefulness of intravenous enoxaparin for percutaneous coronary intervention in stable angina pectoris. Am J Cardiol 1999; 84: 1391–5PubMedCrossRefGoogle Scholar
  40. 40.
    Kereiakes DJ, Grines C, Fry E, et al. Enoxaparin and abciximab adjunctive pharmacotherapy during percutaneous coronary intervention. J Invasive Cardiol 2001; 13(4): 272–8PubMedGoogle Scholar
  41. 41.
    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. Lancet 1998; 352: 87–92Google Scholar
  42. 42.
    Deutsch E, Cohen M, Radley DR, et al. Safety and efficacy of percutaneous procedures in patients receiving subcutaneous enoxaparin for unstable angina: results of the ESSENCE trial [abstract]. Circulation 1998; 98: I–563Google Scholar
  43. 43.
    Collet JP, 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
  44. 44.
    Kereiakes DJ, Kleiman NS, Fry E, et al. Dalteparin in combination with abciximab during percutaneous coronary intervention. Am Heart J 2001; 141: 348–52PubMedCrossRefGoogle Scholar
  45. 45.
    Kaul S, Shah PK. Low molecular weight heparin in acute coronary syndrome: evidence for superior or equivalent efficacy compared with unfractionated heparin? J Am Coll Cardiol 2000; 35: 1699–712PubMedCrossRefGoogle Scholar
  46. 46.
    Martin JL, Fry ET, Sanderink G, et al. Reliable anticoagulation with enoxaparin in patients underoing percutaneous coronary intervention: final PEPCI trial results [abstract]. Am J Cardiol 2002; 90: 158HGoogle Scholar
  47. 47.
    Kereiakes DJ, Montalescot G, Antman EM, 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
  48. 48.
    Bhatt DL, Lincoff AM on behalf of the CRUISE investigators. Combined use of eptifibatide and enoxaparin in patients undergoing percutaneous coronary intervention: the results of the CRUISE trial. Circulation 2001; 104: 11–384Google Scholar
  49. 49.
    Bittl JA, Strony J, Brinker JA, et al. Treatment with bivalirudin (Hirulog) as compared with heparin during coronary angioplasty for unstable or postinfarction angina. Hirulog Angioplasty Study Investigators. N Engl J Med 1995; 333: 764–9Google Scholar
  50. 50.
    Bittl JA, Chaitman BR, 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
  51. 51.
    Lincoff AM, Kleiman NS, 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
  52. 52.
    Lincoff AM, Bittl JA, Kleiman NS, et al. The REPLACE 1 trial: a pilot study of bivalirudin versus heparin during percutaneous coronary intervention with stenting and GP IIb/IIIa blockade. J Am Coll Cardiol 2002; 39: 16A, 1053CrossRefGoogle Scholar
  53. 53.
    Hall P, Nakamura S, Maiello L, et al. A randomized comparison of combined ticlopidine and aspirin therapy versus aspirin therapy alone after successful intravascular ultrasound-guided stent implantation. Circulation 1996; 93: 215–22PubMedCrossRefGoogle Scholar
  54. 54.
    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: 1084–9PubMedCrossRefGoogle Scholar
  55. 55.
    Leon MG, 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: 1665–7Google Scholar
  56. 56.
    Mueller C, Buttner JH, Peterson J, et al. A randomized comparison of clopidogrel and aspirin versus ticlopidine and aspirin after the placement of coronary artery stents. Circulation 2000; 101: 590–3CrossRefGoogle Scholar
  57. 57.
    Machraoui A, Germing A, Lindstaedt M, et al. Efficacy and safety of ticlopidine monotherapy versus ticlopidine and aspirin after coronary artery stenting. Follow-up results of a randomized study. J Invasive Cardiol 2001; 13: 431–6Google Scholar
  58. 58.
    Steinhubl SR, Ellis SG, Wolski K, et al. Ticlopidine pretreatment before coronary stenting is associated with sustained decrease in adverse cardiac events: data from the Evaluation of Platelet IIb/IIIa Inhibitor for Stenting (EPISTENT) Trial. Circulation 2001; 103: 1403–9PubMedCrossRefGoogle Scholar
  59. 59.
    Seyfarth HJ, Koksch M, Roething G, et al. Effect of 300- and 450-mg clopidogrel loading doses on membrane and soluble P-selectin in patients undergoing coronary stent implantation. Am Heart J 2002 Jan; 143(1): 118–23PubMedCrossRefGoogle Scholar
  60. 60.
    Neumann F, Gawaz M, Dickfeld T, et al. Antiplatelet effect of ticlopidine after coronary stenting. J Am Coll Cardiol 1997; 29: 1515–9PubMedCrossRefGoogle Scholar
  61. 61.
    Gregorini L, Marko J, Fajadet J, et al. Ticlopidine attenuates post stent implantation thrombin generation [abstract]. J Am Coll Cardiol 1996; 27: 334ACrossRefGoogle Scholar
  62. 62.
    De Caterina R, Sicari R, Bernini W, et al. Benefit/risk profile of combined antiplatelet therapy with ticlopidine and aspirin. Thromb Haemost 1991; 65: 504–10PubMedGoogle Scholar
  63. 63.
    Bertrand ME, Rupprecht HJ, 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 Aug 8; 102(6): 624–9PubMedCrossRefGoogle Scholar
  64. 64.
    Bhatt DL, Bertrand ME, Berger PB, et al. Meta-analysis of randomized and registry comparisons of ticlopidine with clopidogrel after stenting. J Am Coll Cardiol 2002; 39: 9–14PubMedCrossRefGoogle Scholar
  65. 65.
    Smith SC, Dove JT, Jacobs AK, et al. ACC/AHA Guidelines for Percutaneous Coronary Intervention [revision of the 1993 PTCA guidelines — executive summary]. Circulation 2001; 103: 3019–41PubMedCrossRefGoogle Scholar
  66. 66.
    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: 527–33PubMedCrossRefGoogle Scholar
  67. 67.
    Chew DP, Bhatt DL, Robbins MA, et al. Effect of clopidogrel added to aspirin before percutaneous coronary intervention on the risk associated with C-reactive protein. Am J Cardiol 2001; 88: 672–4PubMedCrossRefGoogle Scholar
  68. 68.
    Assali AR, Salloum J, Sdringola S, et al. Effects of clopidogrel pretreatment before percutaneous coronary intervention in patients treated with glycoprotein IIb/IIIa inhibitors (abciximab or tirofiban). Am J Cardiol 2001; 88: 884–6PubMedCrossRefGoogle Scholar
  69. 69.
    Topol EJ, Ferguson JJ, Weisman HF, et al. Long-term protection from myocardial ischemic events in a randomized trial of brief integrin beta3 blockade with percutaneous coronary intervention. EPIC Investigator Group. Evaluation of Platelet IIb/IIIa Inhibition for Prevention of Ischemic Complication. JAMA 1997; 278: 479–84Google Scholar
  70. 70.
    Topol EJ, Lincoff AM, Kereiakes DJ, et al. Multi-year followup] of abciximab therapy in three randomized, placebo-controlled trials of percutaneous coronary revascularization. Am J Med 2002; 113: 1–6PubMedCrossRefGoogle Scholar
  71. 71.
    Lincoff AM, Tcheng JE, Califf RM, 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. Evaluation in PTCA to Improve Long-term Outcome with abciximab GP IIb/IIIa blockade. Circulation 1999; 99: 1951–8Google Scholar
  72. 72.
    Topol EJ, Mark DB, Lincoff AM, et al. Outcomes at 1 year and economic implications of platelet glycoprotein IIb/IIIa blockade in patients undergoing coronary stenting: results from a multicentre randomised trial. EPISTENT Investigators. Evaluation of Platelet IIb/IIIa Inhibitor for Stenting. Lancet 1999; 354: 2019–24Google Scholar
  73. 73.
    Anderson KM, Califf RM, Stone GW, et al. Long-term mortality benefit with abciximab in patients undergoing percutaneous coronary intervention. J Am Coll Cardiol 2001; 37: 2059–65PubMedCrossRefGoogle Scholar
  74. 74.
    O’ Shea JC, Hafley GE, Greenberg S, et al. Platelet glycoprotein IIb/IIIa integrin blockade with eptifibatide in coronary stent intervention: the ESPRIT trial: a randomized controlled trial. JAMA 2001; 285: 2468–73CrossRefGoogle Scholar
  75. 75.
    O’Shea JC, Buller CE, Cantor WJ, et al. Long-term efficacy of platelet glycoprotein IIb/IIIa integrin blockade with eptifibatide in coronary stent intervention. JAMA 2002; 287: 618–21PubMedCrossRefGoogle Scholar
  76. 76.
    Topol EJ, Moliterno DJ, Herrmann HC, 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
  77. 77.
    Bhatt DL, Marso SP, Lincoff AM, et al. Abciximab reduces mortality in diabetes following percutaneous coronary intervention. J Am Coll Cardiol 2000; 35: 922–8PubMedCrossRefGoogle Scholar
  78. 78.
    Roffi M, Chew DP, Mukherjee D, et al. Platelet glycoprotein IIb/IIIa inhibitors reduce mortality in diabetic patients with non-ST-segment-elevation acute coronary syndromes. Circulation 2001; 104: 2767–71PubMedCrossRefGoogle Scholar

Copyright information

© Adis Internotionol Limited 2002

Authors and Affiliations

  • Joseph K. Choo
    • 1
  • John J. Young
    • 1
  • Dean J. Kereiakes
    • 1
  1. 1.The Lindner Center for Research and Education and the Ohio Heart Health CenterCincinnatiUSA

Personalised recommendations