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Role of platelet inhibitor therapy in myocardial infarction

Cardiovascular Drugs and Therapy volume 3, pages 797–813 (1989)Cite this article

Summary

Atherosclerotic plaque disruption is the predominant pathogenetic mechanism underlying the acute coronary syndromes. Plaque rupture leads to the exposure of collagen and vessel media, resulting in platelet and clotting activation, and occlusive thrombus formation. While drugs that interfere with platelet activation and function have been available for years, more powerful agents with novel mechanisms of action are being developed. Of the available platelet inhibitor drugs, only aspirin, sulfinpyrazone, and dipyridamole have undergone extensive clinical testing in patients with cardiovascular disease. More recently ticlopidine, a new and potent platelet inhibitor, has been successfully tested in patients with coronary and vascular disease.

In acute myocardial infaction, aspirin significantly reduces cardiovascular mortality and reinfarction. Furthermore, the combination of aspirin and a thrombolytic agent produces maximal benefit. A role for heparin in the prevention of early mortality and reinfaction is emerging. This drug is effective for the prevention of left ventricular thrombosis in patients with anterior myocardial infarction.

In the secondary prevention of reinfarction and cardiovascular mortality, available data support the use of a platelet inhibitor. Trials have shown that aspirin is as effective alone as in combination with dipyridamole, and is probably more effective than sulfinpyrazone. Long-term anticoagulant therapy also appears to be beneficial, but is associated with a high cost, need for extensive monitoring, and potential for hemorrhagic side effects.

The role of aspirin in primary prevention is controversial. It may be indicated for patients at high risk for coronary disease in whom the benefit of therapy may outweigh the potential risk of cerebral bleeding.

Coronary atherosclerotic plaque rupture, associated with thrombus formation, is fundamental to the development of acute myocardial infarction. Based on this concept, the role of antithrombotic therapy for the prevention or treatment of ischemic events in patients with coronary artery disease has stimulated enormous interest among clinicians and basic investigators. In this review we will examine: a) the pathogenesis of coronary thrombosis, b) the pharmacology of plateletinhibitor agents, and c) their role in the management of patients with acute myocardial infarction and in primary and secondary prevention of cardiovascular disease.

Platelets interact with both the coagulation and fibrinolytic systems in the pathogenesis of thrombosis. While the purpose of this review is to discuss the role of platelets and platelet inhibitors in coronary disease, the use of anticoagulant or thrombolytic agents will be analyzed briefly when pertinent.

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References

  1. Hawiger J. Formation and regulation of platelet and fibrin hemostatis plug.Human Pathol 1987: 18:111–122.

    Google Scholar 

  2. Zucker MB, Nachmias VT: Platelet activation.Arteriosclerosis 1985; 5:2–18.

    PubMed  Google Scholar 

  3. Mayne R. Collagenous proteins of blood vessels.Arteriosclerosis 1986; 6:585–593.

    PubMed  Google Scholar 

  4. White JG. Platelet structural physiology: The ultrastructure of adhesion. secretion, and aggregation in arterial thrombosis. In: Mehta JL (ed.)Thrombosis and Platelets in Myocardial Ischemia. Cardiovascular Clinics. Philadelphia: F.A. Davis, 1987:13–33.

    Google Scholar 

  5. Vermylen J, Verstraete M, Fuster V. Role of platelet activation and fibrin formation in thrombogenesis.J Am Coll Cardiol 1986; 8 (Suppl B):2B-9B.

    PubMed  Google Scholar 

  6. Peerschke EIB. The platelet fibrinogen receptor.Semin Hematol 1986; 22:241–259.

    Google Scholar 

  7. Coller BS. Activation affects access to the platelet receptor for adhesive glycoproteins.J Cell Biol 1986; 103:451–456.

    PubMed  Google Scholar 

  8. Moncada S, Vane JR. Arachidonic acid metabolites and the interactions between platelets and blood-vessel walls.N Engl J Med 1979; 300:1142–1147.

    PubMed  Google Scholar 

  9. Fuster V, Badimon L, Cohen M, et al. Insights into the pathogenesis of acute ischemic syndromes.Circulation 1988; 77:1213–1220.

    PubMed  Google Scholar 

  10. Adams PC, Fuster V, Badimon L, et al. Platelet vessel wall interactions, rheologic factors and thrombogenic substrate in acute coronary syndromes: Preventive strategies.Am J Cardiol 1987; 60 (Suppl G):9G-16G.

    PubMed  Google Scholar 

  11. Badimon L, Badimon JJ, Galvez A, et al. Influence of arterial wall damage and wall shear rate on platelet deposition: Ex vivo study in a swine modelArteriosclerosis 1986; 6:312–320.

    PubMed  Google Scholar 

  12. Davies MJ, Thomas AC. Plaque fissuring—the cause of acute myocardial infarction, sudden ischemic death, and crescendo angina.Br Heart J 1985; 53:363–373.

    PubMed  Google Scholar 

  13. Falk E. Plaque rupture with severe pre-existing stenosis precipitating coronary thrombosis. Characteristics of coronary atherosclerotic plaques underlying fatal occlusive thrombi.Br Heart J 1983; 50:127–134.

    PubMed  Google Scholar 

  14. Levin DC, Fallon JT. Significance of the angiographic morphology of localized coronary stenoses: Histopathologic correlations.Circulation 1982; 66:316–320.

    PubMed  Google Scholar 

  15. Ambrose JA, Winters SL, Stern A, et al. Angiographic morphology and the pathogenesis of unstable angina pectoris.J Am Coll Cardiol 1985; 5:609–616.

    PubMed  Google Scholar 

  16. Sherman CT, Litvack F, Grundfest W, et al. Coronary angioscopy in patients with unstable angina pectoris.N Engl J Med 1986; 315:913–919.

    PubMed  Google Scholar 

  17. Ambrose JA, Winters SL, Arora RR, et al. Angiographic evolution of coronary artery morphology in unstable angina.J Am Coll Cardiol 1986; 7:472–478.

    PubMed  Google Scholar 

  18. Ambrose JA, Tannenbaum MA, Alexopoulos D, et al. Angiographic progression of coronary artery disease and the development of myocardial infarction.J Am Coll Cardiol 1988; 12:56–62.

    PubMed  Google Scholar 

  19. Little WC, Constantinescu M, Applegate RJ, et al. Can coronary angiography predict the site of a subsequent myocardial infarction in patients with mild-to-moderate coronary artery disease?Circulation 1988; 78:1157–1166.

    PubMed  Google Scholar 

  20. Capone G, Wolf NM, Meyer B, et al. Frequency of intracoronary filling defects by angiography in angina pectoris at rest.Am J Cardiol 1985; 56:403–406.

    PubMed  Google Scholar 

  21. Fitzgerald DJ, Roy L, Catella F, et al. Platelet activation in unstable coronary disease.N Engl J Med 1986; 315:983–989.

    PubMed  Google Scholar 

  22. Theroux P, Latour J-G, Leger C, et al. Fibrinopeptide A and platelet factor levels in unstable angina pectoris.Circulation 1987; 75:156–162.

    PubMed  Google Scholar 

  23. Gotoh K, Minamino T, Hatoh O, et al. The role of intracoronary thrombus in unstable angina: Angiographic assessment and thrombolytic therapy during ongoing anginal attacks.Circulation 1988; 77:526–534.

    PubMed  Google Scholar 

  24. Gibson RS, Beller GA, Gheorghiade M, et al. The prevalence and clinical significance of residual myocardial ischemia 2 weeks after uncomplicated non-Q wave infarction: A prospective natural history study.Circulation 1986; 73:1186–1198.

    PubMed  Google Scholar 

  25. Timmis AD, Griffin B, Crick JCP, et al. The effects of early coronary patency on the evolution of myocardial infarction: A prospective arteriographic study.Br Heart J 1987; 58:345–351.

    PubMed  Google Scholar 

  26. DeWood MA, Stifter WF, Simpson CS, et al. Coronary arteriographic findings soon after non-Q-wave myocardial infarction.N Engl J Med 1986; 315:417–423.

    PubMed  Google Scholar 

  27. Davies MJ. Thrombosis and coronary atherosclerosis. In: Julian DG, Kubler W, Norris RM, et al. (eds.)Thrombolysis in Cardiovascular Disease. New York: Marcel Dekker, 1989:24–43.

    Google Scholar 

  28. Badimon L, Badimon JJ, Turitto VT, et al. Mechanisms of arterial thrombosis: Platelet thrombus deposition in areas of stenosis (abstract).Circulation 1987; 76 (Suppl IV):IV-102.

    Google Scholar 

  29. Francis CW, Markahm RE Jr, Barlow GH, et al. Thrombin activity of fibrin thrombi and soluble plasmic derivatives.J Lab Clin Med 1983; 102:220–230.

    PubMed  Google Scholar 

  30. Harker LA, Fuster V. Pharmacology of platelet inhibitors.J Am Coll Cardiol. 1986; 8 (Suppl B):21B-32B.

    PubMed  Google Scholar 

  31. Moncada S, Vane JR. Pharmacology and endogenous roles of prostaglandin endoperoxides, thromboxane A2 and prostacyclin.Pharmacol Rev 1978; 30:293–331.

    PubMed  Google Scholar 

  32. Burch JW, Stanford PW, Inhibition of platelet prostaglandin synthetase by oral aspirin.J Clin Invest 1979; 61:314–319.

    Google Scholar 

  33. Hanson SR, Harker LA, Bjornsson TD. Effect of plateletmodifying drugs on arterial thromboembolism in baboons. Aspirin potentiates the antithrombotic actions of dipyridamole and sulfinpyrazone by mechanism(s) independent of platelet cyclooxygenase inhibition.J Clin Invest 1985; 75:1591–1599.

    PubMed  Google Scholar 

  34. Buchanan MR, Riscke JA, Hirsh J. Aspirin inhibits platelet function independent of the acetylation of cyclooxygenase.Thromb Res 1982; 25:363–373.

    PubMed  Google Scholar 

  35. Roth GL, Majerus PW. The mechanism of the effect of aspirin on human platelets. I. Acetylation of a particular fraction protein.J Clin Invest 1975; 56:624–632.

    PubMed  Google Scholar 

  36. Jaffe EA, Weksler BB. Recovery of endothelial cell prostacyclin production after inhibition by low doses of aspirin.J Clin Invest 1979; 63:532–535.

    PubMed  Google Scholar 

  37. Preston FE, Whipps S, Jackson CA, et al. Inhibition of prostacyclin and platelet thromboxane A2 after low-dose aspirin.N Engl J Med 1981; 304:76–79.

    PubMed  Google Scholar 

  38. Kyrle PA, Eichler HG, Jager U, et al. Inhibition of prostacyclin and thromboxane A2 generation by low-dose aspirin at the site of plug formation in man in vivo.Circulation 1987; 75:1025–1029.

    PubMed  Google Scholar 

  39. Clowes AW, Karnovsky MJ. Failure of certain antiplatelet drugs to affect myointimal thickening following arterial endothelial injury in the rate.Lab Invest 1977; 36:452–464.

    PubMed  Google Scholar 

  40. UK-TIA Study Group. United Kingdom transient ischaemic attack (UK-TIA) aspirin trial: Interim results.Br Med J 1988; 296:316–320.

    Google Scholar 

  41. Antiplatelet Trialists' Collaboration. Secondary prevention of vascular disease by prolonged antiplatelet treatment.Br Med J 1988; 296:320–331.

    Google Scholar 

  42. Hirsh J, Salzman EW, Harker L, et al. Aspirin and other platelet active drugs. Relationship among dose, effectiveness, and side effects.Chest 1989; 95 (Suppl):12S-18S.

    PubMed  Google Scholar 

  43. Graham DY, Smith LJ. Aspirin and the stomach.Ann Intern Med 1986; 104:390–398.

    PubMed  Google Scholar 

  44. Friedman PL, Brown EJ, Gunther S, et al. Coronary vasoconstrictor effect of indomethacin in patients with coronary artery disease.N Engl J Med 1981; 305:1171–1175.

    PubMed  Google Scholar 

  45. Moncada S, Korbut R, Dipyridamole and other phosphodiesterase inhibitors act as antithrombotic agents by potentiating endogenous prostacyclin.Lancet 1978; 1:1286–1289.

    PubMed  Google Scholar 

  46. Crutchley DJ, Ryan US, Ryan JW. Effects of aspirin and dipyridamole on the degradation of adenosine diphosphate by cultured cells derived from bovine pulmonary artery.J Clin Invest 1980; 66:29–35.

    PubMed  Google Scholar 

  47. FitzGerald GA. Dipyridamole.N Engl J Med 1987; 316:1247–1257.

    PubMed  Google Scholar 

  48. The Persantine-Aspirin Reinfarction Study Group. Persantine and aspirin in coronary heart disease.Circulation 1980; 62:449–461.

    Google Scholar 

  49. Bousser MG, Eschwege E, Haugenau M, et al. “AICLA” controlled trial of aspirin and dipyridamole in the secondary prevention of atherothrombotic cerebral ischemia.Stroke 1983; 14:5–14.

    PubMed  Google Scholar 

  50. American-Canadian Cooperative Study Group. Persantine-aspirin trial in cerebral ischemia. Part II: Endpoint results.Stroke 1985; 16:406–415.

    Google Scholar 

  51. Brown BG, Cukingnan RA, DeRouen T, et al. Improved graft patency in patients treated with platelet-inhibiting therapy after coronary bypass surgery.Circulation 1985; 72:138–146.

    PubMed  Google Scholar 

  52. Goldman S, Copeland J. Moritz T, et al. Improvement in early saphenous vein graft patency after coronary artery bypass surgery with antiplatelet therapy: Results of a Veterans Administration Cooperative Study.Circulation 1988; 77:1324–1332.

    PubMed  Google Scholar 

  53. Hess H, Mietaschk A, Deichsel G. Drug-induced inhibition of platelet function delays progression of peripheral occlusive arterial disease: A prospective double-blind ateriographically controlled trial.Lancet 1985; 1:415–419.

    PubMed  Google Scholar 

  54. Harker LA, Slichter SJ. Studies of platelet and fibrinogen kinetics in patients with prosthetic heart valves.N Engl J Med 1970; 283:1302–1305.

    PubMed  Google Scholar 

  55. Sullivan JM, Harken DE, Gorlin R. Pharmacologic control of thromboembolic complications of cardiac-valve replacement.N Engl J Med 1971; 284:1391–1394.

    PubMed  Google Scholar 

  56. Chesebro JH, Fuster V, Elveback LR, et al. Trial of combined warfarin plus dipyridamole or aspirin therapy in prosthetic heart valve replacement. Danger of aspirin compared with dipyridamole.Am J Cardiol 1983; 51:1537–1541.

    PubMed  Google Scholar 

  57. Steele PP, Rainwater J, Vogel R. Platelet suppressant therapy in patients with prosthetic cardiac valves: Relationship of clinical effectiveness to alteration of platelet survival time.Circulation 1979; 60:910–913.

    PubMed  Google Scholar 

  58. Kaegi A, Pineo GF, Shimizu A, et al. Arteriovenous-shunt thrombosis: Prevention by sulfinpyrazone.N Engl J Med 1974; 290:304–306.

    PubMed  Google Scholar 

  59. Report from the Anturan Reinfarction Italian Study. Sulfinpyrazone in post-myocardial infarction.Lancet 1982; 1:237–242.

    Google Scholar 

  60. Cairns JA, Gent M, Singer J, et al. Aspirin, sulfinpyrazone, or both in unstable angina.N Engl J Med 1985; 313:1369–75.

    PubMed  Google Scholar 

  61. Canadian Cooperative Study Group. A randomized trial of aspirin and sulfinpyrazone in threatened stroke.N Engl J Med 1978; 299:53–59.

    Google Scholar 

  62. Lee H, Paton RC, Ruan C. The in vitro effect of ticlopidine on fibrinogen and factor VIII binding to human platelets (abstract).Thromb Haemost 1981; 46:67.

    Google Scholar 

  63. O'Brien JR. Ticlopidine, a promise for the prevention and treatment of thrombosis and its complications.Haemostatis 1983; 13:1–54.

    Google Scholar 

  64. Violi F, Scrutinio, D, Cimminello C, et al. Study of Ticlopidine in Unstable Angina (S.T.A.I.) (abstract).J Am Coll Cardiol 1989; 13(suppl A):238A.

    Google Scholar 

  65. White CW, Chaitman B, Lassar TA, et al. Antiplatelet agents are effective in reducing the immediate complications of PTCA: Results from the ticlopidine multicenter trial (abstract).Circulation 1987; 76 (Suppl IV):IV-400.

    Google Scholar 

  66. Limet R, David JL, Magotteaux P, et al. Prevention of aorta-coronary bypass graft occlusion.J Thorac Cardiovasc Surg 1987; 94:773–783.

    PubMed  Google Scholar 

  67. Gent M, Blakely JA, Easton JD, et al. The Canadian American Ticlopidine Study (CATS) in thromboembolic stroke.Lancet 1989; 1:1215–1220.

    PubMed  Google Scholar 

  68. Hass WK, Eston JD, Adams HP, et al. A randomized trial comparing ticlopidine hydrochloride with aspirin for the presentation of stroke in high-risk patients.N Engl J Med 1989; 321:501–507.

    PubMed  Google Scholar 

  69. Von Schacky C. Prophylaxis of atherosclerosis with marine omega-3 fatty acids. A comprehensive strategy.Ann Intern Med 1987; 107:890–899.

    PubMed  Google Scholar 

  70. Leaf A, Weber PC. Cardiovascular effects in n-3 fatty acids.N Engl J Med 1988; 318:549–557.

    PubMed  Google Scholar 

  71. Reuben SR, Kuan P, Cairns T, et al. Effects of dazoxiben and exercise performance in chronic stable angina.Br J Clin Pharmacol 1983; 15 (Suppl 1):83S-86S.

    PubMed  Google Scholar 

  72. Thaulow E, Dale J, Myhre E. Effects of a selective thromboxane synthetase inhibitor, dazoxiben, and of acetylsalicylic acid on myocardial ischemia in patients with coronary artery disease.Am J Cardiol 1984: 53:1255–1258.

    PubMed  Google Scholar 

  73. Gresele P, Van Houtte E, Arnout J, et al. Thromboxane synthase inhibition combined with thromboxane receptor blockade. A step forward in antithrombotic strategy.Thromb Haemost 1984; 52:364.

    PubMed  Google Scholar 

  74. Smith MC, Danviriyasup K, Crow JW, et al: Prostacyclin substitution for heparin in long-term hemodialysis.Am J Med 1982; 73:669–678.

    PubMed  Google Scholar 

  75. Coppe D, Sobel M, Seavans L, et al. Preservation of platelet function and number by prostacyclin during cardiopulmonary bypass.J Thorac Cardiovasc Surg 1981; 81:274–278.

    PubMed  Google Scholar 

  76. Uchida Y, Hanai T, Hasewaga K, et al. Recanalization of obstructed coronary artery by intracoronary administration of prostacyclin in patients with acute myocardial infarction.Adv Prostaglandin Thromboxand Leukotriene Res 1983; 11:377–383.

    Google Scholar 

  77. Topol EJ, Califf RM, George BS, et al. Insights derived from the Thrombolysis and Angioplasty in Myocardial Infarction (TAMI) trials.J Am Coll Cardiol 1988; 12 (Suppl A):24A-31A.

    PubMed  Google Scholar 

  78. Fisher CA, Kappa JR, Sinha AK, et al. Comparison of equimolar concentrations of iloprost. prostacyclin, and prostaglandin E1 on human platelet function.J Lab Clin Med 1987; 109:184–190.

    PubMed  Google Scholar 

  79. Roberts WC, Buja LM. The frequency and significance of coronary arterial thrombi and other observations in fatal acute myocardial infarction. A study of 107 necropsy patients.Am J Med 1972; 52:425–443.

    PubMed  Google Scholar 

  80. Bini A, Fenoglio JJ, Mesa-Tejada R, et al. Identification and distribution of fibrinogen. fibrin, and fibrin(ogen) degradation products in atherosclerosis. Use of monoclonal antibodies.Arteriosclerosis 1989; 9:109–121.

    PubMed  Google Scholar 

  81. ISIS-2 (Second International Study of Infarct Survival) Collaborative Group. Randomized trial of intravenous streptokinase, oral aspirin, both, or neither among 17, 187 cases of suspected acute myocardial infarction: ISIS-2.Lancet 1988; 2:349–360.

    Google Scholar 

  82. Lewis HD, Davis JW, Archibald DG, et al. Protective effects of aspirin against acute myocardial infarction and death in men with unstable angina. Results of a Veterans Administration Cooperative Study.N Engl J Med 1983; 309:396–403.

    PubMed  Google Scholar 

  83. Theroux P, Ouimet H, McCans J, et al. Aspirin, heparin, or both to treat acute unstable angina.N Engl J Med 1988; 319:1105–1111.

    PubMed  Google Scholar 

  84. Report of the Working Party on Anticoagulation Therapy in Coronary Thrombosis to the Medical Researh Council. Assessment of short-term anticoagulation administration after cardiac infarction.Br Med J 1969; 1:335–342.

    Google Scholar 

  85. Drapkin A, Merskey C. Anticoagulation therapy after acute myocardial infarction. Relation of therapeutic benefit to patient's age, sex and severity of infarction.JAMA 1972; 222:541–548.

    PubMed  Google Scholar 

  86. Veterans Administration Hospital Investigators. Anticoagulants in acute myocardial infarction. Results of a cooperative clinical trial.JAMA 1973; 225:724–729.

    Google Scholar 

  87. Chalmers TC, Matta RJ, Smith H, et al. Evidence favoring the use of anticoagulants in the hospital phase of acute myocardial infarction.N Engl J Med 1977; 297:1091–1096.

    PubMed  Google Scholar 

  88. Turpie AGG, Robinson JG, Doyle DJ, et al. Comparision of high-dose with low-dose subcutaneous heparin to prevent left ventricular mural thrombosis in patients with acute transmural anterior myocardial infarction.N Engl J Med 1989; 320:352–357.

    PubMed  Google Scholar 

  89. The SCATI (Studio Sulla Calciparina nell'Angina & nella Trombosi Ventricolare nell'Imparto) Group. Randomised controlled trial of subcutaneous calcium-haparin in acute myocardial infarction.Lancet 1989; 2:182–186.

    Google Scholar 

  90. Telford AM, Wilson C. Trial of heparin versus atenolol in prevention of myocardial infarction in intermediate coronary syndrome.Lancet 1981; 1:1225–1228.

    PubMed  Google Scholar 

  91. Ambrose JA, Hjemdahl-Monsen CE, Borrico S, et al. Angiographic demonstration of a common link between unstable angina pectoris and non-Q wave acute myocardial infarction.Am J Cardiol 1988; 61:244–247.

    PubMed  Google Scholar 

  92. Johennessen KA, Stratton JR, Taulow E, et al. Usefulness of aspirin plus dipyridamole in reducing left ventricular thrombus formation in anterior wall acute myocardial infarction.Am J Cardiol 1989; 63:101–102.

    PubMed  Google Scholar 

  93. Fuster V, Stein B, Badimon L, et al. Antithrombotic therapy after myocardial reperfusion in acute myocardial infarction.J Am Coll Cardiol 1988; 12 (Suppl A):78A-84A.

    PubMed  Google Scholar 

  94. Gash AK, Spann JF, Sherry S, et al. Factors influencing reocclusion after coronary thrombolysis for acute myocardial infarction.Am J Cardiol 1986; 57:175–177.

    PubMed  Google Scholar 

  95. Harrison DG, Ferguson DW, Collins SM, et al. Rethrombosis after reperfusion with streptokinase: Importance of geometry of residual lesions.Circulation 1984; 69:991–999.

    PubMed  Google Scholar 

  96. Badger RS, Brown BG, Kennedy JW, et al. Usefulness of recanalization of 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; 59:519–522.

    PubMed  Google Scholar 

  97. De Guise P, Theroux P, Bonan R, et al. Re-thrombosis after successful thrombolysis and angioplasty in acute myocardial infarction (abstract).J Am Coll Cardiol 1988; 11 (Suppl A):192A.

    Google Scholar 

  98. TIMI Study Group. Comparison of invasive and conservative strategies after treatment with intravenous tissue plasminogen activator in acute myocardial infarction. Results of the Thrombolysis in Myocardial Infarction (TIMI) phase II trial.N Engl J Med 1989; 320:618–627.

    Google Scholar 

  99. Elwood PC, Cochrane AL, Burr ML, et al. A randomized controlled trial of acetylsalicylic acid in the secondary prevention of mortality from myocardial infarction.Br Med J 1974; 1:436–440.

    PubMed  Google Scholar 

  100. Coronary Drug Project Group. Aspirin in coronary heart disease.J Chronic Dis 1976; 29:625–642.

    Google Scholar 

  101. Uberla K. Multicenter two-year prospective study onthe prevention of secondary myocardial infarction by ASA in comparison with phenprocoumon and placebo. In: Breddin K, Dorndorf W, Loew D, et al. (eds.)Acetylsalicylic Acid in Cerebral Ischemia and Coronary Heart Disease. Stuttgart: Schattauer, 1978:157–169.

    Google Scholar 

  102. Breddin K, Loew D, Lechner K, et al. The German-Austrian Aspirin Trial: A comparison of acetylsalicylic acid, placebo and phenprocoumon in secondary prevention of myocardial infarction.Circulation 1980; 62 (Suppl V):V63-V72.

    PubMed  Google Scholar 

  103. Elwood PC, Sweetnam PM. Aspirin and secondary mortality after myocardial infarction.Lancet 1979; 2:1313–1315.

    PubMed  Google Scholar 

  104. Aspirin Myocardial Infarction Study Research Group. A randomized, controlled trial of aspirin in persons recovered from myocardial infarction.JAMA 1980; 243:661–669.

    Google Scholar 

  105. The Anturane Reinfarction Trial Research Group. Sulfinpyrazone in the prevention of sudden death after myocardial infarction.N Engl J Med 1980; 302:250–256.

    Google Scholar 

  106. The Anturane Reinfarction Trial: Reevaluation of outcome.N Engl J Med 1982; 306:1005–1008.

    Google Scholar 

  107. Klimt CR, Knatterud GL, Stamler J, et al. Persantine-Aspirin Reinfarction Study. Part II. Secondary coronary prevention with persantine and aspirin.J Am Coll Cardiol 1986; 7:251–269.

    PubMed  Google Scholar 

  108. Peto R. Aspirin after myocardial infarction (editorial).Lancet 1980; 1:1172–1173.

    PubMed  Google Scholar 

  109. Second Report of the Working Party on Anticoagulant Therapy in Coronary Thrombosis to the Medical Research Council. An assessment of long-term anticoagulant administration after cardiac infarction.Br Med J 1964; 2:837–843.

    Google Scholar 

  110. Ebert RV, Borden CW, Hipp HR, et al. Long-term anticoagulant therapy after myocardial infarction. Final report of the Veterans Administration Cooperative Study.JAMA 1969; 207:2263–2267.

    PubMed  Google Scholar 

  111. Report of the Sixty Plus Reinfarction Study Research Group. A double-blind trial to assess long-term oral anticoagulant therapy in elderly patients after myocardial infarction.Lancet 1980; 2:989–993.

    Google Scholar 

  112. An International Anticoagulant Review Group. Collaborative analysis of long-term anticoagulant administration after acute myocardial infarction.Lancet 1970; 1:203–209.

    Google Scholar 

  113. Smith P, Arnesan H. Oral anticoagulants reduce mortality, reinfarction and cerebrovascular events after myocardial infarction—WARIS Study (abstract).Eur Heart J 1989; 10(suppl):264.

    Google Scholar 

  114. 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; 307:701–708.

    Google Scholar 

  115. The 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; 321:129–135.

    Google Scholar 

  116. Peto R, Gray R, Collins R, et al. A randomized trial of the effects of prophylactic daily aspirin among male British doctors.Br Med J 1988; 296:313–316.

    Google Scholar 

  117. Fuster V, Cohen M, Halparin JL. Aspirin in the prevention of coronary disease.N Engl J Med 1989; 321:183–185.

    PubMed  Google Scholar 

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  1. Chief, Division of Cardiology, Mount Sinai Medical Center, One Gustave L. Levy Pl., 10029, New York, NY, USA

    Bernardo Stein & Valentin Fuster MD

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Stein, B., Fuster, V. Role of platelet inhibitor therapy in myocardial infarction. Cardiovasc Drug Ther 3, 797–813 (1989). https://doi.org/10.1007/BF01869563

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Key Words

  • aspirin
  • secondary prevention
  • acute myocardial infarction
  • plaque rupture, platelet inhibitors
  • platelet adhesion
  • aggregation coronary thrombosis