Coronary Atherothrombosis: Pathophysiology and Clinical Implications

  • Avi Fischer
  • David E. Gutstein
  • Zahi A. Fayad
  • Valentin Fuster
Part of the Basic Science for the Cardiologist book series (BASC, volume 2)


The past two decades have witnessed a significant improvement in post-myocardial infarction (MI) survival in the United States. Significant decreases in mortality have been noted in several other countries, as well. The progressive improvement in survival after MI began prior to the introduction of thrombolytic therapy and appears to be related to a variety of improvements in the care of cardiac patients. Most recently, these advances in patient care have included improvements in post-MI medical therapy, revascularization techniques and risk reduction.


Acute Coronary Syndrome Acute Myocardial Infarction Atherosclerotic Plaque Unstable Angina Atherosclerotic Lesion 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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  1. 1.
    Goldberg RJ, Gorak EJ, Yarzebski J, et al. A communitywide perspective of sex differences and temporal trends in the incidence and survival rates after acute myocardial infarction and out-of-hospital deaths caused by coronary heart disease. Circulation 1993; 87:1947–53.PubMedGoogle Scholar
  2. 2.
    Gillum RF. Trends in acute myocardial infarction and coronary heart disease death in the United States. J Am Coll Cardiol 1994; 23:1273–7.PubMedGoogle Scholar
  3. 3.
    Gheorghiade M, Ruzumna P, Borzak S, Havstad S, Ali A, Goldstein S. Decline in the rate of hospital mortality from acute myocardial infarction: impact of changing management strategies. Am Heart J 1996; 131:250–6.PubMedGoogle Scholar
  4. 4.
    Thom TJ, Epstein FH. Heart Disease, cancer, and stroke mortality trends and their interpretations: an international perspective. Circulation 1994; 90:574–82.PubMedGoogle Scholar
  5. 5.
    Naylor CD, Chen E. Population-wide mortality trends among patients hospitalized for acute myocardial infarction: the Ontario experience, 1981 to 1991. J Am Coll Cardiol 1994; 24:1431–8.PubMedGoogle Scholar
  6. 6.
    Dellborg M, Eriksson P, Riha M, Swedberg K. Declining hospital mortality in acute myocardial infarction. European Heart Journal 1994; 15:5–9.PubMedGoogle Scholar
  7. 7.
    Behar S, Barbash GI, Copel L, Gottlieb S, Goldbourt U. Improved survival of hospitalized patients with acute myocardial infarction from 1981-1983 to 1992 in Israel. Coronary Artery Disease 1994; 5:1001–7.PubMedGoogle Scholar
  8. 8.
    Gottleib S, Goldbourt U, Boyko V, et al. Improved outcome of elderly patients (≥75 years of age) with acute myocardial infarction from 1981-1983 to 1992-1994 in Israel. Circulation 1997; 95:342–50.Google Scholar
  9. 9.
    Stary HC, Chandler AB, Dinsmore RE, et al. A definition of advanced types of atherosclerotic lesions and a histologie classification of atherosclerosis: a report from the Committee on Arteriosclerosis, American Heart Association. Circulation 1995; 92:1355–74.PubMedGoogle Scholar
  10. 10.
    Fuster V, Fallon JT, Nemerson Y. Coronary thrombosis. Lancet 1996; 348 (Suppl):s7–s10.PubMedGoogle Scholar
  11. 11.
    Gutstein DE, Fuster V. The pathophysiology and clinical significance of atherosclerotic plaque rupture. Cardiovasc Res in press.Google Scholar
  12. 12.
    Richardson PD, Davies MJ, Born GV. Influence of plaque configuration and stress distribution on fissuring of coronary atherosclerotic plaques. Lancet 1989; 2:1462–3.Google Scholar
  13. 13.
    Ambrose JA, Tannenbaum M, Alexpoulos D, et al. Angiographic progression of coronary artery disease and the development of myocardial infarction. J Am Coll Cardiol 1988; 12:56–62.PubMedGoogle Scholar
  14. 14.
    Fuster V. Lewis A. Conner Memorial Lecture. Mechanisms leading to myocardial infarction: insights from studies of vascular biology. Circulation 1994; 90:2126–46.PubMedGoogle Scholar
  15. 15.
    Fuster V, Badimon L, Badimon JJ, Chesebro JH. The pathogenesis of coronary artery disease and the acute coronary syndromes. N Engl J Med 1992; 326:310–318.PubMedGoogle Scholar
  16. 16.
    Ross R. The Pathogenesis of Atherosclerosis: A perspective for for the 1990’s. Nature 1993; 362:801–808.PubMedGoogle Scholar
  17. 17.
    Steinberg D. Antioxidants and atherosclerosis: a current assessment. Circulation 1991; 84:1420–1425.PubMedGoogle Scholar
  18. 18.
    Steinberg D. Antioxidants in the prevention of human atherosclerosis. Circulation 1992; 85:2338.Google Scholar
  19. 19.
    Rosenfeld ME, Pestel E. Cellularity of atherosclerotic lesions. Cor Art Dis 1994; 5:189–197.Google Scholar
  20. 20.
    Navab M, Hama SY, Nguyen TB, Fogelman AM. Monocyte adhesion and transmigration in atherosclerosis. Cor Art Dis 1994; 5:198–204.Google Scholar
  21. 21.
    van der Wal AC, Becker AE, van der Loos CM, Das PK. Site of intimai rupture or erosion of thrombosed coronary atherosclerotic plaques is characterized by an inflammatory process irrespective of the dominant plaque morphology. Circulation 1994; 89:36–44.PubMedGoogle Scholar
  22. 22.
    Moreno PR, Falk E, Palacios IF, Newell JB, Fuster V, Fallon JT. Macrophage infiltration in acute coronary syndromes: implications for plaque rupture. Circulation 1994; 90:775–8.PubMedGoogle Scholar
  23. 23.
    Falk E, Shah PK, Fuster V. Coronary plaque disruption. Circulation 1995; 92:657–71.PubMedGoogle Scholar
  24. 24.
    Shah PK, Falk E, Badimon JJ, et al. Human monocyte-derived macrophages induce collagen breakdown in fibrous caps of atherosclerotic plaques: potential role of matrix-degrading metalloproteinases and implications for plaque rupture. Circulation 1995; 92:1565–9.PubMedGoogle Scholar
  25. 25.
    Galis ZS, Sukhova GK, Kranzhofer R, Clark S, Libby P. Macrophage foam cells from experimental atheroma constitutively produce matrix-degrading proteinases. Proc Natl Acad Sci USA 1995; 92:402–6.PubMedGoogle Scholar
  26. 26.
    Libby P. Molecular basis of the acute coronary syndromes. Circulation 1995; 91:2844–50.PubMedGoogle Scholar
  27. 27.
    Rajagopalan S, Meng XP, Ramasamy S, Harrison DG, Galis ZS. Reactive oxygen species produced by macrophage-derived foam cells regulate the activity of vascular matrix metalloproteinases in vivo: implications for atherosclerotic plaque stability. J Clin Invest 1996; 98:2572–9.PubMedGoogle Scholar
  28. 28.
    Schecter AD, Rollins BJ, Zhang YJ, et al. Tissue factor is induced by monocyte chemoattractant protein-1 in human aortic smooth muscle and THP-1 cells. J Biol Chem 1997; 272:28568–73.PubMedGoogle Scholar
  29. 29.
    Bjorkerud S, Bjorkerud B. Apoptosis is abundant in human atherosclerotic lesions, especially in inflammatory cells (macrophages and T cells), and may contribute to the accumulation of gruel and plaque instability. Am J Pathol 1996; 149:367–80.PubMedGoogle Scholar
  30. 30.
    Melnick JL, Adam E, DeBakey ME. Possible role of cytomegalovirus in atherogenesis. JAMA 1990; 263:2204–7.PubMedGoogle Scholar
  31. 31.
    Pasceri V, Cammarota G, Patti G, et al. Association of virulent Helicobacter pylori strains with ischemic heart disease. Circulation 1998; 97:1675–79.PubMedGoogle Scholar
  32. 32.
    Campbell LA, O’Brien ER, Cappuccio AL, et al. Detection of Chlamydia pneumoniae TWAR in human coronary atherectomy tissues. J Infect Dis 1995; 172:585–8.PubMedGoogle Scholar
  33. 33.
    Gupta S, Leatham EW, Carrington D, Mendall MA, Kaski JC, Camm AJ. Elevated Chlamydia pneumoniae antibodies, cardiovascular events, and azithromycin in male survivors of myocardial infarction. Circulation 1997; 96:404–7.PubMedGoogle Scholar
  34. 34.
    Gurfinkel E, Bozovich G, Daroca A, Beck E, Mautner B, Group ftRS. Randomized trial of roxithromycin in non-Q-wave coronary syndromes: ROXIS pilot study. Lancet 1997; 350:404–7.PubMedGoogle Scholar
  35. 35.
    Wang P, Ba ZF, Chaudry IH. Administration of tumor necrosis factor-α in vivo depresses endothelium-dependent relaxation. Am J Physiol 1994; 266:H2535–41.PubMedGoogle Scholar
  36. 36.
    Bhagat K, Moss R, Collier J, et al. Endothelial’ stunning’ following a brief exposure to endotoxin: a mechanism to link infection and infarction? Cardiovasc Res 1996; 32:822–9.PubMedGoogle Scholar
  37. 37.
    Smith PD, Saini SS, Raffeld M, Manischewitz JF, Wahl SM. Cytomegalovirus induction of tumor necrosis factor-α by human monocytes and mucosal macrophages. J Clin Invest 1992; 90:1642–1648.PubMedGoogle Scholar
  38. 38.
    Witzum JL, Steinberg D. Role of oxidized low density lipoprotein in atherogenesis. J Clin Invest 1991; 88:1785–92.Google Scholar
  39. 39.
    Lapenna D, de Gioia S, Ciofani G, et al. Glutathione-related antioxidant defenses in human atherosclerotic plaques. Circulation 1998; 97:1930–4.PubMedGoogle Scholar
  40. 40.
    Han DKM, Haudenschild CC, Hong MK, Tinkle BT, Leon MB, Liau G. Evidence for apoptosis in human atherogenesis and in a rat vascular injury model. Am J Pathol 1995; 147:267–77.PubMedGoogle Scholar
  41. 41.
    Kockx MM, De Meyer GRY, Muhring J, Jacob W, Bult H, Herman AG. Apoptosis and related proteins in different stages of human atherosclerotic plaques. Circulation 1998; 97:2307–15.PubMedGoogle Scholar
  42. 42.
    Geng YJ, Wu Q, Muszynski M, Hansson GK, Libby P. Apoptosis of vascular smooth muscle cells induced by in vitro stimulation with interferon-γ, tumor necrosis factor-α, and interleukin-1β. Arterioscler Thromb Vase Biol 1996; 16:19–27.Google Scholar
  43. 43.
    Kockx MM, De Meyer GR, Buyssens N, Knaapen MW, Bult H, Herman AG. Cell composition, replication, and apoptosis in atherosclerotic plaques after 6 months of cholesterol withdrawal. Circ Res 1998; 83:378–87.PubMedGoogle Scholar
  44. 44.
    Fernandez-Ortiz A, Badimon JJ, Falk E, et al. Characterization of the relative thrombogenicity of atherosclerotic plaque components: implications for consequences of plaque rupture. J Am Coll Cardiol 1994; 23:1562–9.PubMedGoogle Scholar
  45. 45.
    Banner DW, D’Arcy A, Chene C, et al. The crystal structure of the complex of blood coagulation factor Vila with soluble tissue factor. Nature 1996; 380:41–6.PubMedGoogle Scholar
  46. 46.
    Theroux P, Fuster V. Acute coronary syndromes: unstable angina and non-Q-wave myocardial infarction. Circulation 1998; 97:1195–1206.PubMedGoogle Scholar
  47. 47.
    Braunwald E, Jones RH, Mark DB, et al. Diagnosing and managing unstable angina. Circulation 1994; 90:613–22.PubMedGoogle Scholar
  48. 48.
    Aguirre FV, Younis LL, Chaitman BR, et al. Early and 1-year clinical outcome of patients evolving non-Q-wave versus Q-wave myocardial infarction after thrombolysis: results from the TIMI II study. Circulation 1995; 91:2541–48.PubMedGoogle Scholar
  49. 49.
    Zareba W, Moss AJ, Raubertas RF. Risk of subsequent cardiac events in stable convalescing patients after first non-Q-wave and Q-wave myocardial infarction. Coron Artery Dis 1994; 5:1009–18.PubMedGoogle Scholar
  50. 50.
    Braunwald E. Unstable angina: a classification. Circulation 1989; 80:410–4.PubMedGoogle Scholar
  51. 51.
    Davies MJ, Thomas A. Thrombosis and acute coronary artery lesions in sudden cardiac ischemic death. N Engl J Med 1984; 310:1137–40.PubMedGoogle Scholar
  52. 52.
    Demirovic J, Myerburg RJ. Epidemiology of sudden coronary death: an overview. Prog Cardiovasc Dis 1994; 37:39–48.PubMedGoogle Scholar
  53. 53.
    Janse MJ, Wit AL. Electrophysiological mechanisms of ventricular arrhythmias resulting from myocardial ischemia and infarction. Physiol Rev 1989; 69:1049–1169.PubMedGoogle Scholar
  54. 54.
    Opitz CF, Mitchell GF, Pfeffer MA, Pfeffer JM. Arrhythmias and death after coronary occlusion in the rat: continuous telemetric ECG monitoring in conscious, untethered rats. Circulation 1995; 92:253–61.PubMedGoogle Scholar
  55. 55.
    Davies MJ. Anatomic features in victims of sudden coronary death: coronary artery pathology. Circulation 1992; 85(Suppl I):I-19–I-24.Google Scholar
  56. 56.
    Vanantiz JM, Becker AE. Sudden cardiac death and acute pathology of coronary arteries. Eur Heart J 1986; 7:987–91.Google Scholar
  57. 57.
    Warnes CA, Roberts WC. Sudden cardiac death: comparison of patients with to those without coronary thrombosis at necropsy. Am J Cardiol 1984; 54:1206–11.PubMedGoogle Scholar
  58. 58.
    Burke AP, Farb A, Malcom GT, Liang Y, Smialek J, Virmani R. Effect of risk factors on the mechanism of acute thrombosis and sudden coronary death in women. Circulation 1998; 97:2110–6.PubMedGoogle Scholar
  59. 59.
    Gheorghiade M, Bonow RO. Chronic heart failure in the United States: a manifestation of coronary artery disease. Circulation 1998; 97:282–89.PubMedGoogle Scholar
  60. 60.
    Pedersen TR, Kjekshus J, Berg K, et al. Cholesterol lowering and the use of healthcare resources: results of the Scandinavian Simvastatin Survival Study. Circulation 1996; 93:1796–802.PubMedGoogle Scholar
  61. 61.
    Bots ML, Hoes AW, Koudstaal PJ, Hofman A, Grobbee DE. Common carotid intima-media thickness and risk of stroke and myocardial infarction: the Rotterdam Study. Circulation 1997; 96:1432–7.PubMedGoogle Scholar
  62. 62.
    O’Leary DH, Polak JF, Kronmal RA, Manolio TA, Burke GL, Wolfson SKJ. Carotid-artery intima and media thickness as a risk factor for myocardial infarction and stroke in older adults. N Engl J Med 1999; 340:14–22.PubMedGoogle Scholar
  63. 63.
    Vallabhajosula S, Fuster V. Atherosclerosis: imaging techniques and the evolving role of nuclear medicine. J Nucl Med 1997; 38:1788–96.PubMedGoogle Scholar
  64. 64.
    Ambrose JA. Angiographie correlations of advanced coronary lesions in acute coronary syndromes. In: Fuster V, ed. Syndromes of atherosclerosis: correlations of clinical imaging and pathology. Armonk, NY: Futura Publishing Co., Inc., 1996:105–22.Google Scholar
  65. 65.
    Feld S, Ganim M, Cavell ES, et al. Comparison of angioscopy intra-vascular ultrasound imaging and quantitative coronary angiography in predicting clinical outcome after coronary intervention in high-risk patients. J Am Coll Cardiol 1996; 28:97–105.PubMedGoogle Scholar
  66. 66.
    Taylor AJ, O’Mally PG. Self-referral of patients for electron-beam computed tomography to screen for coronary artery disease. N Engl J Med 1998; 339:2018–9.PubMedGoogle Scholar
  67. 67.
    Budoff MJ, Georgiou D, Brody A, et al. Ultrafast computed tomography as a diagnostic modality in the detection of coronary artery disease: a multicenter study. Circulation 1996; 93:898–904.PubMedGoogle Scholar
  68. 68.
    Rumberger JA, Sheddy PE, Breen JF, Schwartz RS. Electron beam computed tomographic coronary calcium score cutpoints and severity of associated angiographie lumen stenosis. J Am Coll Cardiol 1997; 29:1542–8.PubMedGoogle Scholar
  69. 69.
    Achenbach S, Moshage W, Ropers D, Nossen J, Daniel WG. Value of electron-beam computed tomography for the noninvasive detction of high-grade coronary-artery stenosis and occlusions. N Engl J Med 1998; 339:1964–71.PubMedGoogle Scholar
  70. 70.
    Callister TQ, Raggi P, Cooil B, Lippolis NJ, Russo DJ. Effect of HMG-CoA reductase inhibitors on coronary artery disease as assessed by electron-beam computed tomography. N Engl J Med 1998; 339:1972–8.PubMedGoogle Scholar
  71. 71.
    Fiorino AS. Electron-beam computed tomography, coronary artery calcium, and evaluation of patients with coronary artery disease. Ann Intern Med 1998; 128:839–47.PubMedGoogle Scholar
  72. 72.
    Celermajer DS. Noninvasive detection of atherosclerosis. N Engl J Med 1998; 339:2014–5.PubMedGoogle Scholar
  73. 73.
    Wexler L, Brundage B, Crouse J, et al. Coronary artery calcification: pathophysiology, epidemiology, imaging methods, and clinical implications: a statement for health professionals from the American Heart Association. Circulation 1996; 94:1175–92.PubMedGoogle Scholar
  74. 74.
    Fayad ZA, Fallon JT, Shinnar M, et al. Noninvasive in vivo high-resolution magnetic resonance imaging of atherosclerotic lesions in genetically engineered mice. Circulation 1998; 98:1541–7.PubMedGoogle Scholar
  75. 75.
    Toussaint JF, Southern JF, Fuster V, Kantor HL. T2-weighted contrast for NMR characterization of human atherosclerosis. Arterioscler Thromb 1995; 15:1533–42.Google Scholar
  76. 76.
    Toussaint JF, LaMuraglia GM, Southern JF, et al. Magnetic resonance images lipid, fibrous, calcified, hemorrhagic and thrombotic components of human atherosclerosis in vivo. Circulation 1996; 1994:932–8.Google Scholar
  77. 77.
    Skinner MP, Yuan C, Mitsumori L, et al. Serial magnetic resonance imaging of experimental atherosclerosis detects lesion fine structure, progression and complications in vivo. Nat Med 1995; 1:69–73.PubMedGoogle Scholar
  78. 78.
    Pennell DJ, Bogren HG, Keegan J, et al. Assessment of coronary stenosis by magnetic resonance imaging. Heart 1996; 75:127–33.PubMedGoogle Scholar
  79. 79.
    Fayad ZA, Nahar T, Badimon JJ, et al. In-Vivo MR characterization of plaques in the thoracic aorta. Circulation 1998; 98:1–515.Google Scholar
  80. 80.
    Shepherd J, Cobbe SM, Ford I, et al. Prevention of coronary heart disease with pravastatin in men with hypercholesterolemia: West of Scotland Coronary Prevention Study Group. N Engl J Med 1995; 333:1301–7.PubMedGoogle Scholar
  81. 81.
    Scandinavian Simvastatin Survival Study Group. Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S). Lancet 1994; 344:1383–89.Google Scholar
  82. 82.
    The Cholesterol and Recurrent Events (CARE) Trial Investigators. The effect of pravastatin on coronary events after myocardial infarction in patients with average cholesterol levels. N Engl J Med 1996; 335:1001–9.Google Scholar
  83. 83.
    Fuster V, Badimon JJ. Regression or stabilization of atherosclerosis means regression or stabilization of what we don’t see in the arteriogram. Eur Heart J 1995; 16:6–12.PubMedGoogle Scholar
  84. 84.
    Waters D. Review of cholesterol-lowering therapy: coronary angiographic and events trials. Am J Med 1996; 101 (suppl 4A):34S–39S.Google Scholar
  85. 85.
    Gotto AM. Cholesterol management in theory and practice. Circulation 1997; 96:4424–30.PubMedGoogle Scholar
  86. 86.
    Fuster V, Fallon JT, Badimon JJ, Nemerson Y. The unstable atherosclerotic plaque: clinical significance and therapeutic intervention. Thromb Haemost 1997; 78:247–55.PubMedGoogle Scholar
  87. 87.
    Small DM, Bond MG, Waugh D, Prack M, Sawyer JK. Physicochemical and histological changes in the arterial wall of nonhuman primates during progression and regression of atherosclerosis. J Clin Invest 1984; 73:1590–605.PubMedGoogle Scholar
  88. 88.
    Kaplan JR, Manuck SB, Adams MR, Williams JK, Register TC, Clarkson TB. Plaque changes and arteriet alnlargement in atherosclerotic monkeys after manipulation of diet and societ alnvironment. Arterioscler Thromb 1993; 13:254–63.PubMedGoogle Scholar
  89. 89.
    Aikawa M, Rabkin E, Okada Y, et al. Lipid lowering by diet reduces matrix metalloproteinase activity and increases collagen content of rabbit atheroma: a potential mechanism of lesion stabilization. Circulation 1998; 97:2433–44.PubMedGoogle Scholar
  90. 90.
    Ryan TJ, Anderson JL, Antman EM, et al. ACC/AHA guidelines for the management of patients with acute myocardial infarction: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on Management of Acute Myocardial Infarction). J Am Coll Cardiol 1996; 28:1328–428.PubMedGoogle Scholar
  91. 91.
    The E.P.S.I.M. Research Group. A controlled comparison of aspirin and oral anticoagulants in prevention of death after myocardial infarction. N Engl J Med 1982; 307:701–8.Google Scholar
  92. 92.
    The Coumadin Aspirin Reinfarction Study (CARS) Investigators. Randomised double-blind trial of fixed low-dose warfarin with aspirin after myocardial infarction. Lancet 1997; 350:389–96.Google Scholar
  93. 93.
    Prentice CRM. Antithrombotic therapy in the secondary prevention of myocardial infarction. Am J Cardiol 1993; 72:175G–180G.Google Scholar
  94. 94.
    Gutstein DE, Fuster V. Pathophysiologic bases for adjunctive therapies in the treatment and secondary prevention of acute myocardial infarction. Clin Cardiol 1998; 21:161–8.PubMedGoogle Scholar
  95. 95.
    ISIS (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; 2:349–60.Google Scholar
  96. 96.
    Gruppo Italiano per lo Studio della Streptochinasi Nell’Infarto Miocardico (GISSI). Effectiveness of intravenous thrombolytic treatment in acute myocardial infarction. Lancet 1986; 1:397–402.Google Scholar
  97. 97.
    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; 89:1545–56.Google Scholar
  98. 98.
    Mizuno K, Satomura K, Miyamoto A, et al. Angioscopic evaluation of coronary artery thrombi in acute coronary syndromes. N Engl J Med 1992; 326:287–91.PubMedGoogle Scholar
  99. 99.
    Antiplatelet Trialists’ Collaboration. Collaborative overview of randomised trials of antiplatelet therapy-I: prevention of death, myocardial infarction, and stroke by prolonged antiplatelet therapy in various categories of patients. BMJ 1994; 308:81–106.Google Scholar
  100. 100.
    Theroux P, Ouimet H, McCans J, et al. Aspirin, heparin or both to treat acute unstable angina. N Engl J Med 1988; 319:1105–11.PubMedGoogle Scholar
  101. 101.
    The RISC Group. Risk of myocardial infarction and death during treatment with low dose aspirin and intravenous heparin in men with unstable coronary disease. Lancet 1990; 336:827–30.Google Scholar
  102. 102.
    Lewis HD, Davis JW, Archibald DG, et al. Protective effects of aspirin against myocardial infarction and death in men with unstable angina. N Engl J Med 1983; 309:396–403.PubMedGoogle Scholar
  103. 103.
    Cairns JA, Gent M, Singer J, et al. Aspirin, sulfinpyrazone, or both in unstable angina. N Engl J Med 1985; 313:1369–75.PubMedGoogle Scholar
  104. 104.
    Cohen M, Adams PC, Parry G, et al. Combination antithrombotic therapy in unstable angina and non-Q-wave infarction in nonprior aspirin users. Circulation 1994; 89:81–8.PubMedGoogle Scholar
  105. 105.
    Oler S, Whooley MA, Oler J, Grady D. Adding heparin to aspirin reduces the incidence of myocardial infarction and death in patients with unstable angina. JAMA 1996; 276:811–5.PubMedGoogle Scholar
  106. 106.
    Organization to Assess Strategies for Ischemic Syndromes (OASIS) Investigators. Comparison of the effects of two doses of recombinant hirudin compared with heparin in patients with acute myocardial ischemia without ST elevation: a pilot study. Circulation 1997; 96:769–77.Google Scholar
  107. 107.
    White HD, Aylward PE, Frey MJ, et al. Randomized, double-blind comparison of hirulog versus heparin in patients receiving streptokinase and aspirin for acute myocardial infarction (HERO). Circulation 1997; 96:2155–61.PubMedGoogle Scholar
  108. 108.
    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; 337:447–52.PubMedGoogle Scholar
  109. 109.
    Fragmin during Instability in Coronary Artery Disease (FRISC) Study Group. Low-molecular-weight heparin during instability in coronary artery disease. Lancet 1996; 347:561–8.Google Scholar
  110. 110.
    The Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO) llb Investigators. A comparison of recombinant hirudin with heparin for the treatment of acute coronary syndromes. N Engl J Med 1996; 335:775–82.Google Scholar
  111. 111.
    The Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO) Ha Investigators. Randomized trial of intravenous heparin versus recombinant hirudin for acute coronary syndromes. Circulation 1994; 90:1631–7.Google Scholar
  112. 112.
    Coller BS. Blockade of platelet GP llb/IIIa receptors as an antithrombotic strategy. Circulation 1995; 92:2373–80.PubMedGoogle Scholar
  113. 113.
    Use of a monoclonal antibody directed against the platelet glycoprotein Ilb/IIIa receptor in high-risk coronary angioplasty: The EPIC Investigation. N Engl J Med 1994; 330:956–61.Google Scholar
  114. 114.
    The CAPTURE Investigators. Randomised placebo-controlled trial of abciximab before and during coronary intervention in refractory unstable angina: The CAPTURE Study. Lancet 1997; 349:1429–35.Google Scholar
  115. 115.
    The EPIC Investigators. 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; 330:956–61.Google Scholar
  116. 116.
    Nicolini FA, Lee P, Rios G, Kottke-Marchant K, Topol EJ. Combination of platelet fibrinogen receptor antagonist and direct antithrombin inhibitor at low doses markedly improves thrombolysis. Circulation 1994; 89:1802–9.PubMedGoogle Scholar
  117. 117.
    Ohman EM, Kleiman NS, Gacioch G, et al. Combined accelerated tissue-plasminogen activator and platelet glycoprotein Ilb/IIIa integrin receptor blockade with integrilin in acute myocardial infarction. Circulation 1997; 95:846–54.PubMedGoogle Scholar
  118. 118.
    Shebuski RJ, Stabilito IJ, Sitko GR, Polokoff MH. Acceleration of recombinant tissue-type plasminogen activator-induced thrombolysis and prevention of reocclusion by the combination of heparin and the Arg-Gly-Asp-containing peptide bitistatin in a canine model of coronary thrombosis. Circulation 1990; 82:169–77.PubMedGoogle Scholar
  119. 119.
    Coller BS. Inhibitors of the platelet glycoprotein Ilb/IIIa receptor as conjunctive therapy for coronary artery thrombolysis. Coron Artery Dis 1992; 3:1016–29.Google Scholar
  120. 120.
    Gold HK, Coller BS, Yasuda T, et al. Rapid and sustained coronary artery recanalization with combined bolus injection of recombinant tissue-type plasminogen activator and monoclonal antiplatelet GP IIb/IIIa antibody in a canine preparation. Circulation 1988; 77:670–7.PubMedGoogle Scholar
  121. 121.
    Toschi V, Gallo R, Lettino M, et al. Tissue factor predicts the thrombogenicity of human atherosclerotic plaque components. Circulation 1997; 95:594–9.PubMedGoogle Scholar

Copyright information

© Kluwer Academic Publishers 1999

Authors and Affiliations

  • Avi Fischer
    • 1
  • David E. Gutstein
    • 1
  • Zahi A. Fayad
    • 1
  • Valentin Fuster
    • 1
  1. 1.Mt. Sinai Medical CenterUSA

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