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Thrombolytic and Antithrombotic Therapies for Acute Coronary Syndromes

  • Chapter
Contemporary Concepts in Cardiology

Part of the book series: Developments in Cardiovascular Medicine ((DICM,volume 217))

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Abstract

Over the past decade, many advances have been made in the understanding of acute coronary syndromes and in the development of thrombolytic and antithrombotic regimens used to improve clinical outcome. Based on their similar pathophysiology, clinical presentation, and treatment strategies, the acute coronary syndromes can be viewed as part of a spectrum of myocardial ischemia, which ranges from stable angina to acute Q wave myocardial infarction (MI).(Figure 8.1) These ischemic syndromes share the same underlying pathophysiology, i.e., the long-term asymptomatic development of atherosclerotic plaques followed by acute plaque activation leading to rupture with superimposed local thrombosis.1–3 Based on the large number of ruptured and healed plaques with layers of thrombus found at autopsy, it is estimated that the vast majority of ruptured plaques are clinically silent, producing only a mild degrees of coronary stenosis.4 In some patients, however, the amount of local thrombosis is more extensive and a flow limiting coronary stenosis results; this process leads to myocardial ischemia, with or without some degree of myocardial necrosis, clinically manifest as unstable angina or a non-Q wave MI. If plaque rupture and thrombosis are extensive, complete occlusion of the coronary artery can occur, producing clinically persistent ischemic pain and ST segment elevation, in patients without adequate collateral circulation, which usually evolves into a Q-wave MI.

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References

  1. Fuster V, et al. The pathophysiology of coronary artery disease and the acute coronary syndromes. N Engl J Med 1992;326: 242, 310.

    Article  PubMed  CAS  Google Scholar 

  2. Falk E. Unstable angina with fatal outcome: dynamic coronary thrombosis leading to infarction and/or sudden death. Circulation 1985;71: 699.

    Article  PubMed  CAS  Google Scholar 

  3. Davies MJ, Thomas A. Plaque fissuring-the cause of acute myocardial infarction, sudden ischemic death, and crescendo angina. Br Heart J 1985;53: 363.

    Article  PubMed  CAS  Google Scholar 

  4. Davies MJ. New insights from pathology studies, presented at the George Washington University Symposium on Thrombolysis and Interventional Therapy in Acute Myocardial Infarction. Dallas, Texas: November, 1994:.

    Google Scholar 

  5. Braunwald E, et al. Unstable Angina: Diagnosis and Management. Clinical Practice Guideline Number 10. Rockville, MD: Agency for Health Care Policy and Research and the National Heart, Lung, and Blood Institute, Public Health Service, U.S. Department of Health and Human Services, 1994: 154.

    Google Scholar 

  6. The TIMI IIIB Investigators. Effects of tissue plasminogen activator and a comparison of early invasive and conservative strategies in unstable angina and non-Q-wave myocardial infarction: Results of the TIMI IIIB Trial. Circulation 1994;89: 1545.

    Article  Google Scholar 

  7. Anderson HV, et al. One-year results of the Thrombolysis in Myocardial Infarction (TIMI) IIIB clinical trial. A randomized comparison of tissue-type plasminogen activator versus placebo and early invasive versus early conservative strategies in unstable angina and non-Q-wave myocardial infarction. J Am Coll Cardiol 1995;26: 1643.

    Article  PubMed  CAS  Google Scholar 

  8. Stone PH, et al. Influence of race, sex, and age on management of unstable angina and non-Q-wave myocardial infarction: The TIMI III Registry. JAMA 1996;275: 1104.

    Article  PubMed  CAS  Google Scholar 

  9. TIMI Research Group. Immediate vs delayed catheterization and angioplasty following thrombolytic therapy for acute myocardial infarction. TIMI II A results. JAMA 1988;260: 2849.

    Article  Google Scholar 

  10. Williams DO, et al. One-year results of the Thrombolysis in Myocardial Infarction Investigation (TIMI) phase II trial. Circulation 1992;85: 533.

    Article  PubMed  CAS  Google Scholar 

  11. Braunwald E, et al. Diagnosing and Managing Unstable Angina. Circulation 1994;90: 613.

    Article  PubMed  CAS  Google Scholar 

  12. Vita JA, et al. Coronary vasomotor response to acetylcholine relates to risk factors for coronary artery disease. Circulation 1990;81: 491.

    Article  PubMed  CAS  Google Scholar 

  13. Anderson TJ, et al. The effect of cholesterol-lowering and antioxidant therapy on endothe-lium-dependent coronary vasomotion. N Engl J Med 1995;332: 488.

    Article  PubMed  CAS  Google Scholar 

  14. Ridker PM, et al. Low-dose aspirin therapy for chronic stable angina. A randomized, placebo-controlled clinical trial. Ann Intern Med 1991;114: 835.

    PubMed  CAS  Google Scholar 

  15. Steering Committee of the Physicians’ Health Study Research Group. Final report on the aspirin component of the ongoing Physicians’ Health Study. N Engl J Med 1989;321: 129.

    Article  Google Scholar 

  16. Manson JE, et al. A prospective study of aspirin use and primary prevention of cardiovascular disease in women. JAMA 1991;266: 521.

    Article  PubMed  CAS  Google Scholar 

  17. Klimt CR, et al. Persantine-Aspirin Reinfarction Study. Part II. Secondary coronary prevention with persantine and aspirin. J Am Coll Cardiol 1986;7: 251.

    Article  PubMed  CAS  Google Scholar 

  18. Willard JE, Lange RA, Hillis LD. The use of aspirin in ischemic heart disease. N Engl J Med 1992;327: 175.

    Article  PubMed  CAS  Google Scholar 

  19. Smith P, Arnesen H, Holme I. The effect of warfarin on mortality and reinfarction after myocardial infarction. N Engl J Med 1990;323: 147.

    Article  PubMed  CAS  Google Scholar 

  20. Antiplatelet Trialist’ Collaboration. Collborative overview of randomised trials of antiplatelet therapy-I: prevention of death myocardial infarction and stroke by prolongued antiplatelet therapy in various categories of patients. BMJ 1994;308: 81.

    Article  Google Scholar 

  21. Lewis HD, et al. Protective effects of aspirin against acute myocardial infarction and death in men with unstable angina. N Engl J Med 1983;309: 396.

    Article  PubMed  Google Scholar 

  22. Cairns JA, et al. Aspirin, sulfinpyrazone, or both in unstable angina. N Engl J Med 1985;313: 1369.

    Article  PubMed  CAS  Google Scholar 

  23. Theroux P, et al. Aspirin, heparin or both to treat unstable angina. N Engl J Med 1988;319: 1105.

    Article  PubMed  CAS  Google Scholar 

  24. The RISC Group. Risk of myocardial infarction and death during treatment with low dose aspirin and intravenous heparin in men with unstable coronary artery disease. Lancet 1990;336: 827.

    Article  Google Scholar 

  25. Theroux P, et al. Reactivation of unstable angina after the discontinuation of heparin. N Engl J Med 1992;327: 141.

    Article  PubMed  CAS  Google Scholar 

  26. Roux S, Christelier S, Ludin E. Effects of aspirin on coronary reocclusion and recurrent ischemia after thrombolysis: a meta-analysis. j Am Coll Cardiol 1992; 19: 671.

    Article  PubMed  CAS  Google Scholar 

  27. ISIS-2 (Second International Study of Infarct Survival) Collaborative Group. Randomised trial of intravenous streptokinase, oral aspirin, both, or neither among 17,187 cases of suspected acute myocardial infarction: ISIS-2. Lancet 1988;2: 349.

    Google Scholar 

  28. Tollefsen DM. Heparin: Basic and clinical pharmacology. In: Hoffman R, Benz EJJ, Shattil SJ, Furie B, Cohen HJ, ed. Hematology: Basic principles and practice. New York: Churchill Livingstone, 1991, pl436–45

    Google Scholar 

  29. Verstraete M. Heparin. In: Messerli FH, ed. Cardiovascular drug therapy. Philadelphia: W.B. Saunders Company, 1990, p1457.

    Google Scholar 

  30. Majerus PW, et al. Anticoagulant, thrombolytic, and antiplatelet drugs. In: Gilman AG, Rail TW, Nies AS, Taylor P, ed. The pharmacological basis of therapeutics. 8th ed. New York: Pergamon Press, 1990, p 102.

    Google Scholar 

  31. Rosenberg RD. The heparin-antithrombin system: a natural anticoagulant mechanism. In: Colman RW, Marder VJ, Salzman EW, Hirsh J, ed. Hemostasis and Thrombosis: Basic Principles and Clinical Practice. 2nd ed. Philadelphia: J.B. Lippincott Company, 1987, p1373.

    Google Scholar 

  32. Hirsh J. Heparin. N Engl J Med 1991;324: 1565.

    Article  PubMed  CAS  Google Scholar 

  33. Ogilby JD, et al. Variability of effective anticoagulation for PTCA is dependent upon heparin potency. Circulation 1991;84: (Suppl II): II–592.

    Google Scholar 

  34. Bock PE, et al. The multiple complexes formed by the interaction of platelet factor 4 with heparin. Biochem J 1980; 191: 769.

    PubMed  CAS  Google Scholar 

  35. Lijnen HR, Hoylaerts M, Collens D. Heparin binding properties of human histidine-rich glycoprotein: mechanism and role in the neutralization of heparin in plasma. J Biol Chem 1983;258: 3803.

    PubMed  CAS  Google Scholar 

  36. Preissner KT, Muller-Berghaus G. Neutralization and binding of heparin by S-protein/vitronectin in the inhibition of factor Xa by antithrombin III. J Biol Chem 1987;262: 12247.

    PubMed  CAS  Google Scholar 

  37. Maraganore JM, et al. Heparin variability and resistance: Comparisons with a direct thrombin inhibitor.(abstract) Circulation 1992;86 (Suppl. I): I–386.

    Google Scholar 

  38. Cruikshank MK, et al. A standard nomogram for the management of heparin therapy. Arch Intern Med 1991;151: 333.

    Article  Google Scholar 

  39. Flaker GC, et al. Use of a standardized nomogram to achieve therapeutic anticoagulation after thrombolytic therapy in myocardial infarction. Arch Intern Med 1994; 154: 1492.

    Article  PubMed  CAS  Google Scholar 

  40. Williams DO, et al. Anticoagulant treatment in unstable angina. Br J Clin Pract 1986;40: 114.

    PubMed  CAS  Google Scholar 

  41. Tedford AM, Wilson C. Trial of heparin versus atenolol in prevention of myocardial infarction in intermediate coronary syndrome. Lancet 1981;1: 1225.

    Article  Google Scholar 

  42. Theroux P, et al. Aspirin versus heparin to prevent myocardial infarction during the acute phase of unstable angina. Circulation 1993;88: 2045.

    Article  PubMed  CAS  Google Scholar 

  43. Cohen M, et al. Combination antithrombotic therapy in unstable rest angina and non-Q-wave infarction in nonprior aspirin users. Primary end points analysis from the ATACS trial. Circulation 1994;89: 81.

    Article  PubMed  CAS  Google Scholar 

  44. Topol EJ, et al. A randomized controlled trial of intravenous tissue plasminogen activator and early intravenous heparin in acute myocardial infarction. Circulation 1989;79: 281.

    Article  PubMed  CAS  Google Scholar 

  45. Hsia J, et al. A comparison between heparin and low-dose aspirin as adjunctive therapy with tissue plasminogen activator for acute myocardial infarction. N Engl J Med 1990;323: 1433.

    Article  PubMed  CAS  Google Scholar 

  46. Bleich SD, et al. Effect of heparin on coronary patency after thrombolysis with tissue plasminogen activator in acute myocardial infarction. Am J Cardiol 1990;66: 1412.

    Article  PubMed  CAS  Google Scholar 

  47. de Bono DP, et al. Effect of early intravenous heparin on coronary patency, infarct size, and bleeding complications after alteplase thrombolysis: results of a randomized double blind European Cooperative Study Group trial. Br Heart J 1992;67: 122.

    Article  PubMed  Google Scholar 

  48. Thompson PL, et al. A randomized comparison of intravenous heparin with oral aspirin and dipyridamole 24 hours after recombinant tissue-type plasminogen activator for acute myocardial infarction. Circulation 1991;83: 1534.

    Article  PubMed  CAS  Google Scholar 

  49. Aguirre F, et al. Influence of intravenous heparin duration on clinical outcome of patients receiving accelerated weight-adjusted rt-PA for acute myocardial infarction: preliminary results of the Multicenter Randomized t-PA Heparin Duration Trial. (abstract) Circulation 1993;88[Pt. 2]: I–201

    Google Scholar 

  50. Gruppo Italiano per lo Studio della Soprawivenza nell’Infarto Miocardico: GISSI-2. A factorial randomised trial of alteplase versus streptokinase and heparin versus no heparin among 12,490 patients with acute myocardial infarction. Lancet 1990;336: 65.

    Google Scholar 

  51. ISIS-3 (Third International Study of Infarct Survival) Collaborative Group. ISIS-3: a randomised comparison of streptokinase vs tissue plasminogen activator vs anistreplase and of aspirin plus heparin vs aspirin alone among 41,299 cases of suspected acute myocardial infarction. Lancet 1992;339: 753.

    Article  Google Scholar 

  52. Ridker PM, et al. Are both aspirin and heparin justified as adjunctions to thrombolytic therapy for acute myocardial infarction? Lancet 1993;341: 1574.

    CAS  Google Scholar 

  53. Kroon C, et al. Highly variable anticoagulant response after subcutaneous administration of high-dose (12,5000 IU) heparin in patients with myocardial infarction and healthy volunteers. Circulation 1992;86: 1370.

    Article  PubMed  CAS  Google Scholar 

  54. Handin RI, Loscalzo J. Hemostasis, thrombosis, fibrinolysis, and cardiovascular disease. In: Braunwald E, ed. Heart Disease, 4th ed. Philadelphia: W.B. Saunders, 1992, p1767.

    Google Scholar 

  55. Goldhaber SZ. Conjunctive heparin therapy. Limitations of sucutaneous administration. Circulation 1992;86: 1639.

    Article  PubMed  CAS  Google Scholar 

  56. Scharfstein JS, et al. Usefulness of fibinogenolytic and procoagulant markers during thrombolytic therapy in predicting clinical outcomes in acute myocardial infarction. Am J Cardiol 1996;78: 503.

    Article  PubMed  CAS  Google Scholar 

  57. Ohman EM, et al. Consequences of reocclusion after successful reperfusion therapy in acute myocardial infarction. Circulation 1990;82: 781.

    Article  PubMed  CAS  Google Scholar 

  58. Gibson CM et al. Angiographic predictors of reocclusion after thrombolysis: results from the Thrombolysis in Myocardial Infarction (TIMI) 4 trial. J Am Coll Cardiol 1995;25: 582.

    Article  PubMed  CAS  Google Scholar 

  59. The GUSTO Investigators. An international randomized trial comparing four thrombolytic strategies for acute myocardial infarction. N Engl J Med 1993;329: 673–82.

    Article  Google Scholar 

  60. The GUSTO Angiographic Investigators. The comparative effects of tissue plasminogen activator, streptokinase, or both on coronary artery patency, ventricular function and survival after acute myocardial infarction. N Engl J Med 1993;329: 1615–22.

    Article  Google Scholar 

  61. Loscalzo J, Braunwald E. Tissue plasminogen activator. N Engl J Med 1988;319: 925.

    Article  PubMed  CAS  Google Scholar 

  62. Marder VJ, Sherry S. Thrombolytic therapy: current status. N Engl J Med 1988;318: 1512, 1585.

    Article  PubMed  CAS  Google Scholar 

  63. Hirsh J, Fuster V. Guide to anticoagulation therapy. Part 1: heparin. Circulation 1994;89: 1449.

    Article  PubMed  CAS  Google Scholar 

  64. Raschke RA, et al. The weight-based heparin dosing nomogram compared with a “standard care” nomogram. ann intern Med 1993; 119: 874.

    PubMed  CAS  Google Scholar 

  65. Neuhaus K-L, et al. Safety obervations from the pilot phase of a randomized trial: r-Hirudin for Improvement of Thromboysis (HIT-III) Study. A study of the Arbeitsgemeinschaft Lei-tender, Kardiologischer Koinkenhausarzte (ALKK). Circulation 1994;90: 1638.

    Article  PubMed  CAS  Google Scholar 

  66. O’Connor CM, et al. A randomized trial of intravenous heparin in conjunction with anistre-plase (Anisoylated Plasminogen Streptokinase Activator Complex) in acute myocardial infarction: the Duke University Clinical Cardiology Study (DUCCS). J Am Coll Cardiol 1994;23: 11.

    Article  PubMed  Google Scholar 

  67. Antman EM, for the TIMI 9A Investigators. Hirudin in acute myocardial infarction: Safety report from the Thrombolysis and Thrombin Inhibition in Myocardial Infarction (TIMI) 9 A trial. Circulation 1994;90: 1624.

    Article  PubMed  CAS  Google Scholar 

  68. The Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO) Ila Investigators. A randomized trial of intravenous heparin versus recombinant hirudin for acute coronary syndromes. Circulation 1994;90: 1631.

    Article  Google Scholar 

  69. Hsia J, et al. Heparin-induced prolongation of partial thromboplastin time after thrombolysis: relationship to coronary artery patency. J Am Coll Cardiol 1992;20: 31.

    Article  PubMed  CAS  Google Scholar 

  70. Arnout J, et al. Correlation between level of heparinization and patency of the infarct-related coronary artery after treatment of acute myocardial infarction with alteplase (rt-PA). J Am Coll Cardiol 1992;20: 513.

    Article  PubMed  CAS  Google Scholar 

  71. Granger C, et al. Activated partialthromboplastin time and outcome after thrombolytic therapy for acute myocardial infarction: results from the GUSTO-I Trial. Circulation 1996;93: 870.

    Article  PubMed  CAS  Google Scholar 

  72. Cannon CP, et al. Usefulness of APTT to predict bleeding for hirudin (and heparin). (abstract) Circulation 1994;90[Pt. 2]: I–563

    Google Scholar 

  73. Cannon CP, et al. Comparison of front-loaded recombinant tissue-type plasminogen activator, anistreplase and combination thrombolytic therapy for acute myocardial infarction: results of the Thrombolysis in Myocardial Infarction (TIMI) 4 trial. J Am Coll Cardiol 1994;24: 1602.

    Article  PubMed  CAS  Google Scholar 

  74. Bovill EG, et al. Hemorrhagic events during therapy with recombinant tissue-type plasminogen activator, heparin, and aspirin for acute myocardial infarction. Results of the Thrombolysis in Myocardial Infarction (TIMI), Phase II trial. Ann Intern Med 1991; 115: 256.

    PubMed  CAS  Google Scholar 

  75. Cannon CP, et al. The Thrombolysis in Myocardial Infarction (TIMI) Trials-the first decade. J Intervent Cardiol 1995;8: 117.

    Article  PubMed  CAS  Google Scholar 

  76. Becker R, et al. Relationship between systemic anticoagulation as determined by activated partial thromboplastin time and heparin measurements and in-hospital clinical events in unstable angina and non-Q wave myocardial infarction. Am Heart J 1996;1131: 421.

    Article  Google Scholar 

  77. Braunwald E. Myocardial reperfusion, limitation of infarct size, reduction of left ventricular dysfunction, and improved survival: Should the paradigm be expanded? Circulation 1989;79: 441.

    Article  PubMed  CAS  Google Scholar 

  78. Braunwald E. Unstable angina: a classification. Circulation 1989;80: 410.

    Article  PubMed  CAS  Google Scholar 

  79. Califf RM, Topol EJ, Gersh BJ. From myocardial salvage to patient salvage in acute myocardial infarction. The role of reperfusion therapy. J Am Coll Cardiol 1989;14: 1382.

    Article  PubMed  CAS  Google Scholar 

  80. Braunwald E. The open-artery theory is alive and well-again. N Engl J Med 1993;329: 1650.

    Article  PubMed  CAS  Google Scholar 

  81. Cannon CP, Braunwald E. GUSTO, TIMI and the case for rapid reperfusion. Acta Cardiol 1994;49: 1.

    PubMed  CAS  Google Scholar 

  82. Dalen JE, et al. Six-and twelve-month follow-up of the Phase I Thrombolysis in Myocardial Infarction (TIMI) Trial. Am J Cardiol 1988;62: 179.

    Article  PubMed  CAS  Google Scholar 

  83. TIMI Study Group. The Thrombolysis in Myocardial Infarction (TIMI) Trial; Phase I findings. N Engl J Med 1985;312: 932.

    Google Scholar 

  84. Flygenring BP, et al. Does arterial patency 90 minutes following thrombolytic therapy predict 42 day survival? J Am Coll Cardiol 1991;17 (Suppl. A): 275A.

    Article  Google Scholar 

  85. Karagounis L, et al. Does Thrombolysis in Myocardial Infarction (TIMI) perfusion grade 2 represent a mostly patent artery or a mostly occluded artery? Enzymatic and electrocardiographic evidence from the TEAM-2 Study. j Am Coll Cardiol 1992; 19: 1.

    Article  PubMed  CAS  Google Scholar 

  86. Gibson CM, et al. TIMI frame count: a quantitive method of assessing coronary artery flow. Circulation 1996;93: 879.

    Article  PubMed  CAS  Google Scholar 

  87. Belenkie I, et al. Importance of effective, early and sustained reperfusion during acute myocardial infarction. Am J Cardiol 1989;63: 912.

    Article  PubMed  CAS  Google Scholar 

  88. Anderson JL, et al. TIMI perfusion grade 3 but not grade 2 results in improved outcome after thrombolysis for myocardial infarction: ventriculographic, enzymatic and electrocardiographic evidence from the TEAM-3 Study. Circulation 1993;87: 1829.

    Article  PubMed  CAS  Google Scholar 

  89. Badger RS, et al. Usefullness of recanalization to luminal diameter of 0.6 millimeter or more with intracoronary streptokinase during acute myocardial infarction in predicting “normal” perfusion status, continued arterial patency and survival at one year. Am J Cardiol 1987;59: 519.

    Article  PubMed  CAS  Google Scholar 

  90. Gibson CM, et al. Consequences of TIMI 2 vs 3 flow at 90 minutes following thrombolysis. J Am Coll Cardiol 1993;21 (Suppl. A): 348A

    Google Scholar 

  91. Lincoff AM, et al. Significance of a coronary artery with Thrombolysis in Myocardial Infarction grade 2 flow “patency” (Outcome in the Thrombolysis and Angioplasty in Myocardial Infarction (TAMI) Trials). Am J Cardiol 1995;75: 81.

    Article  Google Scholar 

  92. Kennedy J, Ritchie J, et al. The Western Washington randomized trial of intracoronary streptokinase in acute myocardial infarction: a 12-month follow-up report. Nejm 1985;312: 1073.

    Article  PubMed  CAS  Google Scholar 

  93. Stadius ML, et al. Risk stratification for 1 year survival based on characteristics identified in the early hours of acute myocardial infarction. Circulation 1986;74: 701.

    Article  Google Scholar 

  94. Vogt A, et al. Impact of early perfusion status of the infarct-related artery on short-term mortality after thrombolysis for acute myocardial infarction: retrospective analysis of four German multicenter studies. J Am Coll Cardiol 1993;21: 1391.

    Article  PubMed  CAS  Google Scholar 

  95. Cannon CP, et al. A pilot trial of recombinant desulfatohirudin compared with heparin in conjunction with tissue-type plasminogen activator and aspirin for acute myocardial infarction: Results of the Thrombolysis in Myocardial Infarction (TIMI) 5 Trial. J Am Coll Cardiol 1994;23: 993.

    Article  PubMed  CAS  Google Scholar 

  96. Gruppo Italiano per lo Studio della Streptochinasi nell’Infarto Miocardico (GISSI). Effectiveness of intravenous thrombolytic treatment in acute myocardial infarction. Lancet 1986;1: 397.

    PubMed  Google Scholar 

  97. AIMS Trial Study Group. Effect of intravenous APSAC on mortality after acute myocardial infarction: Preliminary report of a placebo-controlled clinical trial. Lancet 1988;2: 545.

    Google Scholar 

  98. ASSET Study Group. Trial of tissue plasminogen activator for mortality reduction in acute myocardial infarction. Anglo-Scandinavian Study of Early Thrombolysis (ASSET). Lancet 1988;2: 525.

    Google Scholar 

  99. Fibrinolytic Therapy Trialists (FTT) Collaborative Group. Indications for fibrinolytic therapy in suspected acute myocardial infarction: collaborative overview of early mortality and major morbidity results from all randomised trials of more than 1000 patients. Lancet 1994;343: 311.

    Google Scholar 

  100. Gore JM, et al. Intracerebral hemorrhage, cerebral infarction, and subdural hematoma after acute myocardial infarction and thrombolytic therapy in the Thrombolysis in Myocardial Infarction Study. Thrombolysis in Myocardial Infarction, Phase II, pilot and clinical trial. Circulation 1991;83: 448.

    Article  PubMed  CAS  Google Scholar 

  101. Simoons ML, et al. Individual risk assessment for intracranial hemorrhage during thrombolytic therapy. Lancet 1993;342: 1523.

    Article  PubMed  CAS  Google Scholar 

  102. Maggioni AP, et al. The risk of stroke in patients with acute myocardial infarction after thrombolytic and antithrombotic treatment. N Engl J Med 1992;327: 1.

    Article  PubMed  CAS  Google Scholar 

  103. International Study Group. In-hospital mortality and clinical course of 20,891 patients with suspected acute myocardial infarction randomised between alteplase and streptokinase with or without heparin. Lancet 1990;336: 71.

    Article  Google Scholar 

  104. Neuhaus K-L, et al. Improved thrombolysis with a modified dose regimen of recombinant tissue-type plasminogen activator. J Am Coll Cardiol 1989;14: 1566.

    Article  PubMed  CAS  Google Scholar 

  105. Neuhaus K-L, et al. Improved thrombolysis in acute myocardial infarction with front-loaded administration of alteplase: results of the rt-PA-APSAC Patency Study (TAPS). j Am Coll Cardiol 1992; 19: 885.

    Article  PubMed  CAS  Google Scholar 

  106. Carney RJ, et al. Randomized angiographic trial of recombinant tissue-type plasminogen ctivator (alteplase) in myocardial infarction. J Am Coll Cardiol 1992;20: 17.

    Article  PubMed  CAS  Google Scholar 

  107. Grines CL, et al. A prospective, randomized trial comparing combination half-dose tissue-type plasminogen activator and streptokinase with full-dose tissue-type plasminogen activator. Circulation 1991;84: 540.

    Article  PubMed  CAS  Google Scholar 

  108. Kleiman NS, et al. Mortality within 24 hours of thrombolysis in myocardial infarction. The importance of early reperfusion. Circulation 1994;90: 2658.

    Article  PubMed  CAS  Google Scholar 

  109. Topol EJ, et al. More on the GUSTO trial. N Engl J Med 1994;331: 277.

    Article  PubMed  CAS  Google Scholar 

  110. Braunwald E, Cannon CP, McCabe CH. An approach to evaluating thrombolytic therapy in acute myocardial infarction. The’ Unsatisfactory Outcome’ end point. Circulation 1992;86: 683.

    Article  PubMed  CAS  Google Scholar 

  111. Zarich SW, et al. Sequential low dose conbination thrombolytic therapy: results of the Prouroki-nase and t-PA Enhancement of Thrombolysis (PATENT) trial. (abstract) Circulation 1994;90[Pt. 2]: I–562.

    Google Scholar 

  112. Cannon CP, et al. Time as an adjunctive agent to thrombolytic therapy. J Thromb Thrombolysis 1994;1: 27.

    Article  PubMed  Google Scholar 

  113. Timm TC, et al. Left ventricular function and early cardiac events as a function of time to treatment with t-PA: A report from TIMI II. Circulation 1991;84: 11–230.

    Google Scholar 

  114. National Heart Attack Alert Program Coordinating Committee-60 Minutes to Treatment Working Group. Emergency department: rapid identification and treatment of patients with acute myocardial infarction. Ann Emerg Med 1994;23: 311.

    Article  Google Scholar 

  115. The TIMI IIIA Investigators. Early effects of tissue-type plasminogen activator added to conventional therapy on the culprit lesion in patients presenting with ischemic cardiac pain at rest. Results of the Thrombolysis in Myocardial Ischemia (TIMI IIIA) Trial. Circulation 1993;87: 38.

    Article  Google Scholar 

  116. The RAPT Investigators. Randomized trial of ridogrel, a combined thromboxane A2 synthase inhibitor and thromboxane A2prostaglandin endoperoxide receptor antagonist, versus asprin as adjunction to thrombolysis in patients with acute myocardial infarction. The Ridogrel Aspirin Patency Trial (RAPT). Circulation 1994;89: 588.

    Article  Google Scholar 

  117. Coller BS, Scudder LR. Inhibition of dog platelet function by in vivo infusion of F(ab’)2 fragments of a monoclonal antibody to the platelet glycoprotein IIb/IIIa eceptor. Blood 1985;66: 1456.

    PubMed  CAS  Google Scholar 

  118. Kleiman N, et al. Profound inhibition of platelet aggregation with monoclonal antibody 7E3 Fab after thrombolytic therapy. Results of the Thrombolysis and Angioplasty in Myocardial Infarction (TAMI) 8 pilot study. J Am Coll Cardiol 1993;22: 381.

    Article  PubMed  CAS  Google Scholar 

  119. The EPIC Investigators. Use of a monoclonal antibody directed against the platelet glycoprotein IIb/IIIa receptor in high risk angioplasty. N Engl J Med 1994;330: 956.

    Article  Google Scholar 

  120. Simoons ML, et al. Randomized trial of a GPIIb/IIIa platelet receptor blocker in refractory unstable angina. Circulation 1994;89: 596.

    Article  PubMed  CAS  Google Scholar 

  121. Schulman SP, et al. Effects of Integrelin, a platelet glycoprotein IIb/IIa antagonist, in unstable angina. A randomized multicenter trial. Circulation 1996;94: 2083.

    Article  PubMed  CAS  Google Scholar 

  122. Nicolini FA, et al. Combination of platelet fibrinogen receptor antagonist and direct thrombin inhibitor at low doses markedly improves thrombolysis. Circulation 1994;89: 1802.

    Article  PubMed  CAS  Google Scholar 

  123. Kereiakes DJ, et al. Randomized, double-blind, placebo-controlled dose-ranging study of tirofiban (MK-383) platelet Ilb/IIIa blockade in high risk patients undergoing coronary angioplasty. J Am Coll Cardiol 1996;27: 536.

    Article  PubMed  CAS  Google Scholar 

  124. Theroux P, et al. Platelet membrane receptor glycoprotein Ilb/IIIa antagonism in unstable angina. The Canadian Lamifiban Study. Circulation 1996;94: 899.

    Article  PubMed  CAS  Google Scholar 

  125. Lefkovits J, et al. Effects of platelet glycoprotein IIb/IIIa receptor blockade by a chimeric monoclonal antibody (abciximab) on acute and six-month outcomes after percutaneous transluminal coronary angioplasty for acute myocardial infarction. Am J Cardiol 1996;77: 1045.

    Article  PubMed  CAS  Google Scholar 

  126. Ohman EM, et al. Combined accelerated tissue-plasminogen activator and platelet glycoprotein Ilb/IIa integrin receptor blockade with integrilin in acute myocardial infarction. Circulation 1997;95: 846.

    Article  PubMed  CAS  Google Scholar 

  127. The PRISM-PLUS Investigators. Inhibition of platelet glycoprotein IIb/IIIa with tirofiban in unstable angina and non-Q wave myocardial infarction. N Engl J Med in press.

    Google Scholar 

  128. White HD. Platelet Receptor Inhibition for Ischemic Syndrome Management, presented at the American College of Cardiology Scientific Sessions. Anaheim, CA, 1997

    Google Scholar 

  129. Topol EJ. The Platelet Glycoprotein IIb/IIIa in Unstable Angina: Receptor Suppression Using Integrillin Therapy (PURSUIT) trial, presented at the The European Society of Cardiology Congress. Stockholm, Norway, August 1997.

    Google Scholar 

  130. Markwardt F. Isolierung uber Hirudin. Naturwissenschafter 1955;42: 537.

    Article  Google Scholar 

  131. Maraganore JM, et al. Design and characterization of hirulogs: A novel class of bivalent peptide inhibitors of thrombin. Biochemistry 1990;29: 7095.

    Article  PubMed  CAS  Google Scholar 

  132. Rydel TJ, et al. The structure of a complex of recombinant hirudin and human alpha-throm-bin. Science 1990;249: 277.

    Article  PubMed  CAS  Google Scholar 

  133. Vu T H., et al. Domains specifying thrombin-receptor interaction. Nature 1991;353: 674.

    Article  PubMed  CAS  Google Scholar 

  134. Cannon CP. Hirulog. In: Messerli FH, ed. Cardiovascular Drug Therapy. 2nd ed. Philadelphia: W.B. Saunders Company, 1996: 1498.

    Google Scholar 

  135. Talbot M. Biology of recombinant hirudin (CGP 39393): a new prospect in the treatment of thrombosis. Semin Thromb Hemost 1989;15: 293.

    Article  PubMed  CAS  Google Scholar 

  136. Markwardt F. Past, present and future of hirudin. Haemostasis 1991;21: 11.

    PubMed  CAS  Google Scholar 

  137. Ofosu FA, et al. Inhibition of the amplification reactions of blood coagulation by site-specific inhibitors of alpha-thrombin. Biochem J 1992;283: 893.

    PubMed  CAS  Google Scholar 

  138. Cannon CP. Thrombin inhibitors in acute myocardial infarction. In: Kleiman NS, ed. Cardiology Clinics: Acute Myocardial Infarction. Philadelphia: W.B. Saunders Company, in press.

    Google Scholar 

  139. Weitz JI, et al. Clot-bound thrombin is protected from inhibition by heparin-antithrombin III but is susceptible to inactivation by antithrombin Ill-independent inhibitors. J Clin Invest 1990;86: 385.

    Article  PubMed  CAS  Google Scholar 

  140. Fareed J, et al. Some objective considerations for the neutralization of the anticoagulant effects of recombinant hirudin. Haemostasis 1991;21(Suppl. 1): 64.

    PubMed  CAS  Google Scholar 

  141. Lee LV, for the TIMI 6 Investigators. Initial experience with hirudin and streptokinase in acute myocardial infarction: results of the Thrombolysis in Myocardial Infarction (TIMI) 6 trial. Am J Cardiol 1995;75: 7.

    Article  PubMed  CAS  Google Scholar 

  142. Antman EM, for the TIMI 9B Investigators. Hirudin in acute myocardial infarction: Thrombolysis and Thrombin Inhibition in Myocardial Infarction (TIMI) 9B trial. Circulation 1996;94: 911.

    Article  PubMed  CAS  Google Scholar 

  143. The Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO) lib Investigators. A comparison of recombinant hirudin with heparin for the treatment of acute coronary syndromes. N Engl J Med 1996;335: 775.

    Article  Google Scholar 

  144. Topol EJ, et al. Recombinant hirudin for unstable angina pectoris. A multicenter, randomized angiographic trial. Circulation 1994;89: 1557.

    Article  PubMed  CAS  Google Scholar 

  145. Kaplan K, et al. Role of heparin after intravenous thrombolytic therapy for acute myocardial infarction. Am J Cardiol 1987;59: 241.

    Article  PubMed  CAS  Google Scholar 

  146. Cannon CP, et al. Anticoagulant effects of Hirulog, a novel thrombin inhibitor, in patients with coronary artery disease. Am J Cardiol 1993;71: 778.

    Article  PubMed  CAS  Google Scholar 

  147. Fox I, et al. Anticoagulant activity of HirulogTM, a direct thrombin inhibitor, in humans. Thromb Haemost 1993;69: 157.

    PubMed  CAS  Google Scholar 

  148. Lidon R-M, et al. A pilot, early angiographic patency study using a direct thrombin inhibitor as adjunctive therapy to streptokinase in acute myocardial infarction. Circulation 1994;89: 1567.

    Article  PubMed  CAS  Google Scholar 

  149. Theroux P, et al. Randomized double-blind comparison of two doses of hirulog with heparin as adjunctive therapy to streptokinase to promote early patency of the infarct-related artery in acute myocardial infarction. Circulation 1995;91: 2132.

    Article  PubMed  CAS  Google Scholar 

  150. Sharma GVRK, et al. Usefulness and tolerability of Hirulog, a direct thrombin-inhibitor, in unstable angina pectoris. Am J Cardiol 1993;72: 1357.

    Article  PubMed  CAS  Google Scholar 

  151. Lidon R-M, et al. Initial experience with a direct antithrombin, Hirulog, in unstable angina: anticoagulant, antithrombotic and clinical effects. Circulation 1993;88: 1495.

    Article  PubMed  CAS  Google Scholar 

  152. Fuchs J, Cannon CP, and the TIMI 7 Investigators. Hirulog in the treatment of unstable angina: results of the Thrombin Inhibition in Myocardial Ischemia (TIMI) 7 trial. Circulation 1995;92: 727.

    Article  PubMed  CAS  Google Scholar 

  153. Gold HK, et al. Evidence of a rebound coagulation phenomenon after cessation of a 4-hour infusion of a specific thrombin inhibitor in patients with unstable angina pectoris. J Am Coll Cardiol 1993;21: 1039–47.

    Article  PubMed  CAS  Google Scholar 

  154. FRISC Study Group. Low molecular weight heparin (Fragmin) during istabillity in coronary artery disease (FRISC). Lancet 1996;347: 561.

    Google Scholar 

  155. Cohen M, Demers C, Gurfinkel EP, et al. A comparison of low-molecular-weight heparin with unfractionated heparin for unstable coronary artery disease. N Engl J Med 1997;337: 447.

    Article  PubMed  CAS  Google Scholar 

  156. Baird SH, McBride SJ, Trouton TG, Wilson C. Low-molecular-weight heparin versus unfractionated heparin following thrombolysis in myocardial infarction. J Am Col Cardiol 1998;31 (Suppl. A): 191A.

    Article  Google Scholar 

  157. Granger CB, et al. Rebound increase in thrombin generation and activity after cessation of intravenous heparin in patients with acute coronary syndromes. Circulation 1995; 91: 1929.

    Article  PubMed  CAS  Google Scholar 

  158. Merlini PA, et al. Persistent activation of coagulation mechanism in unstable angina and myocardial infarction. Circulation 1994;90: 61.

    Article  PubMed  CAS  Google Scholar 

  159. Herren T, et al. Fibrin formation and degradation in patients with arteriosclerotic disease. Circulation 1994;90: 2679.

    Article  PubMed  CAS  Google Scholar 

  160. Collen D, Lijnen HR. Staphylokinase, a fibrin-specific plasminogen activator with therapeutic potential? Blood 1994;84: 680.

    PubMed  CAS  Google Scholar 

  161. Vanderschueren S, et al. A randomized trial of recombinant staphylokinase versus alteplase for coronary artery patency in acute myocardial infarction. Circulation 1995;92: 22044.

    Google Scholar 

  162. Bode C, et al. Randomized comparison of coronary thrombolysis achieved with double-bolus reteplase (recombinant plasminogen activator) and front-loaded, accelerated alteplase (recombinant tissue plasminogen activator) in patients with acute myocardial infarction. Circulation 1996;94: 891.

    Article  PubMed  CAS  Google Scholar 

  163. The Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO III) Investigators. A comparison of reteplase with alteplase for acute myocardial infarction. N Engl J Md 1997;337: 1118.

    Article  Google Scholar 

  164. Keyt BA, et al. A faster-acting and more potent form of tissue plasminogen activator. Proc Natl Acad Sci USA 1994;91: 3670.

    Article  PubMed  CAS  Google Scholar 

  165. Cannon CP, et al. TNK-tissue plasminogen activator in acute myocardial infarction: Results of the Thrombolysis in Myocardial Infarction (TIMI) 10A dose-ranging trial. Circulation 1997;95: 351.

    Article  PubMed  CAS  Google Scholar 

  166. Cannon CP, et al. TNK-tissue plasminogen activator compared with front-loaded tissue plasminogen activator in acute myocardial infarction: Primary results of the TIMI 10B trial. (abstract) Circulation 1997;96(Suppl. I): I–206

    Google Scholar 

  167. International Joint Efficacy Comparison of Thrombolytics. Randomised, double-blind comparison of reteplase double-bolus administration with streptokinase in acute myocardial infarction (INJECT): trial to investigate equivalence. Lancet 1995;346: 329.

    Article  Google Scholar 

  168. Lopez-Sendon JL, on behalf of the In TIME Investigations. Intravenous nPA for Treatmen of Infarction Myocardium Early: the In TIME study Eur Heart J 1997;18: 454.

    Google Scholar 

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  1. Christopher P. Cannon
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Cannon, C.P., Loscalzo, J. (1999). Thrombolytic and Antithrombotic Therapies for Acute Coronary Syndromes. In: Contemporary Concepts in Cardiology. Developments in Cardiovascular Medicine, vol 217. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-5007-5_8

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  • DOI: https://doi.org/10.1007/978-1-4615-5007-5_8

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