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Thrombolysis in the Management of Acute Myocardial Infarction and Unstable Angina Pectoris

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Summary

Thrombolytic therapy has recently gained ascendance as an accepted form of treatment for acute myocardial infarction. Since the majority of patients with acute infarction have an occlusive coronary thrombus, plasminogen activators administered to these patients generate plasmin that proteolyses the fibrin elements of the thrombus and thereby reestablishes coronary patency. In addition to the conventional agents streptokinase and urokinase, newer, more fibrin-selective plasminogen activators are currently available for use or study, including tissue plasminogen activator and pro-urokinase.

In acute myocardial infarction, the agents that have been studied most extensively are streptokinase and tissue plasminogen activator. Among the major recent studies of the use of these activators, several important observations have been made, including the need for administration of agent within 3 hours of the onset of pain, the efficacy of the intravenous route of administration, significant reduction in mortality with early administration, and significantly improved left ventricular function with early administration. Haemorrhagic complications remain a problem, but with judicious dosing their incidence can be kept to a minimum. Early studies in patients with unstable angina suggest that plasminogen activators may also have a role in the management of this clot-dependent disorder.

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References

  • Adelman B, Michelson AD, Loscalzo J, Greenberg J, Handin RI. Plasmin effect on platelet glycoprotein Ib-von Willebrand factor interactions. Blood 65: 32–40, 1985

    PubMed  CAS  Google Scholar 

  • Aldrich MS, Sherman SA, Greenberg HS. Cerebrovascular complications of streptokinase infusion. Journal of the American Medical Association 253: 1777–1779, 1985

    Article  PubMed  CAS  Google Scholar 

  • Ambrose JA, Hjemdahl-Monsen C, Burrico S, Sherman W, Cohen M, et al. Quantitative and qualitative effects of intracoronary streptokinase in unstable angina and non-Q wave infarction. Journal of the American College of Cardiology 9: 1156–1165, 1987

    Article  PubMed  CAS  Google Scholar 

  • Anderson JL. Development and evaluation of anisoylated plasminogen streptokinase activator complex (APSAC) as a second generation thrombolytic agent. Journal of the American College of Cardiology 10: 22B-27B, 1987

    Article  Google Scholar 

  • Anderson JL, Rothbard RL, Hackworthy RA, Sorenson SG, Fitzpatrick PG, et al. for the APSAC Multicentre Investigators. Multicenter reperfusion trial of intravenous anisoylated plasminogen streptokinase activator complex (APSAC) in acute myocardial infarction: controlled comparison with intracoronary streptokinase. Journal of the American College of Cardiology 11: 1152–1163, 1988

    Google Scholar 

  • Sakata Y. Influence of alpha-2-plasmin inhibitor on adsorption of plasminogen to fibrin. Thrombosis Research 19: 149–155, 1980

    Article  PubMed  Google Scholar 

  • Bassand JP, Machecourt J, Cassagnes J, Anguenot T, Lusson JR, et al. A multicenter double-blind trial of intravenous APSAC versus heparin in acute myocardial infarction. Journal of the American College of Cardiology 11: 232A, 1988

    Google Scholar 

  • Bode C, Matsueda G, Hui KY, Haber E. Antibody-directed urokinase: a specific fibrinolytic agent. Science 230: 765–767, 1985

    Article  Google Scholar 

  • Booth NA, Walker E, Maughan R, Bennett B. Plasminogen activator in normal subjects after exercise or venous occlusion: tPA circulates as complexes with C1-inhibitor and PAI-1. Blood 69: 1600–1604, 1987

    PubMed  CAS  Google Scholar 

  • Burket MW, Smith MR, Walsh TE, Brewster PS, Fraker Jr TD. Relation of effectiveness of intracoronary thrombolysis in acute myocardial infarction to systemic thrombolytic state. American Journal of Cardiology 56: 441–445, 1985

    Article  PubMed  CAS  Google Scholar 

  • Chesebro JH, Knatterud G, Roberts R, Borer J, Cohen LS, et al. Thrombolysis in Myocardial Infarction (TIMI) Trial, Phase I: a comparison between intravenous tissue plasminogen activator and intravenous streptokinase: clinical findings through hospital discharge. Circulation 76: 147–154, 1987

    Article  Google Scholar 

  • Collen D, Bounameaux H, de Cock F, Lijnen HR, Verstraete M. Analysis of coagulation and fibrinolysis during intravenous infusion of recombinant human tissue-type plasminogen activator in patients with acute myocardial infarction. Circulation 73: 511–517, 1986a

    Article  PubMed  CAS  Google Scholar 

  • Collen D, Stassen J-M, Stump DL, Verstraete M. Synergism of thrombolytic agents in vivo. Circulation 74: 838–842, 1986b

    Article  PubMed  CAS  Google Scholar 

  • Davies MJ, Thomas A. Thrombosis and acute coronary-artery lesions in sudden cardiac ischemic death. New England Journal of Medicine 310: 1137–1140, 1984

    Article  PubMed  CAS  Google Scholar 

  • DeWood MA, Spores J, Notske R, Mouser LT, Burroughs R, et al. Prevalence of total coronary occlusion during the early hours of transmural myocardial infarction. New England Journal of Medicine 303: 897–902, 1980

    Article  PubMed  CAS  Google Scholar 

  • DeWood MA, Stifter WE, Simpson CS, Spores J, Eugster GS, et al. Coronary arteriographic findings soon after non-Q-wave myocardial infarction. New England Journal of Medicine 315: 417–423,1986

    Article  PubMed  CAS  Google Scholar 

  • Dosne AM, Dupuy E, Bodevin E. Production of a fibrinolytic inhibitor by cultured endothelial cells derived from human umbilical vein. Thrombosis Research 12: 377–387, 1978

    Article  PubMed  CAS  Google Scholar 

  • Fitzgerald DJ, Catella F, Roy L, FitzGerald GA. Marked platelet activation in vivo after intravenous streptokinase in patients with acute myocardial infarction. Circulation 77: 142–150, 1988

    Article  PubMed  CAS  Google Scholar 

  • Francis CW, Marder VJ. Physiologic regulation and pathologic disorders of fibrinolysis. In Colman RW et al. (Eds) Hemostasis and thrombosis, p. 359, Lippincott, Philadelphia, 1987

    Google Scholar 

  • Fulton W. I-Labelled fibrinogen, autoradiography and stereoarteriography in identification of coronary thrombotic occlusion. British Heart Journal 38: 880, 1976

    PubMed  CAS  Google Scholar 

  • Garabedian HD, Gold HK, Leinbach RC, Johns JA, Yasuda T, et al. Comparative properties of two clinical preparations of recombinant human tissue-type plasminogen activator in patients with acute myocardial infarction. Journal of the American College of Cardiology 9: 599–607, 1987

    Article  PubMed  CAS  Google Scholar 

  • Gimpel LW, Gold HK, Leinbach RC, Yasuda T, Johns JA, et al. Bleeding time measurement predicts spontaneous bleeding during thrombolysis with recombinant tissue-type plasminogen activator. Journal of the American College of Cardiology 11: 231A, 1988

    Google Scholar 

  • Gold HK, Coller B, Yasuda T, Saito T, Leinbach RC, et al. A monoclonal antibody to the platelet receptor GPIIb/IIIa (7E3) accelerates thrombolysis with recombinant tissue-type plasminogen activator (rt-PA) and prevents coronary reocclusion. Circulation 76: IV–377, 1987a

    Google Scholar 

  • Gold HK, Johns JA, Leinbach RC, Yasuda T, Grossbard E, et al. A randomized, blinded, placebo-controlled trial of recombinant human tissue-type plasminogen activator in patients with unstable angina pectoris. Circulation 75: 1192–1199, 1987b

    Article  PubMed  CAS  Google Scholar 

  • Gold HK, Leinbach RC, Garabedian HD, Yasuda T, Johns JA, et al. Acute coronary reocclusion after thrombolysis with recombinant human tissue-type plasminogen activator: prevention by maintenance infusion. Circulation 73: 347–352, 1986

    Article  PubMed  CAS  Google Scholar 

  • Golder JP, Stephens RW. Miniactivin: a human monocyte product which specifically inactivates urokinase-type plasminogen activator. European Journal of Biochemistry 136: 517–522, 1983

    Article  PubMed  CAS  Google Scholar 

  • Gruppo Italiano per lo Studio della Streptochinasi nell Infarto Miocardio (GISSI). Effectiveness of intravenous thrombolytic treatment in acute myocardial infarction. Lancet 1: 397–402, 1986

    Google Scholar 

  • Guerci AD, Gerstenblith G, Brinker JA, Chandra NC, Gottlieb SO, et al. A randomized trial of intravenous tissue plasminogen activator for acute myocardial infarction with subsequent randomization to elective coronary angioplasty. New England Journal of Medicine 317: 1613–1618, 1987

    Article  PubMed  CAS  Google Scholar 

  • Gurewich V, Pannell R, Louie S, Kelley P, Suddith RL, et al. Effective and fibrin-specific clot lysis by a zymogen precursor form of urokinase (pro-urokinase). Journal of Clinical Investigation 73: 1731–1739, 1984

    Article  PubMed  CAS  Google Scholar 

  • Holvoet P, Lijnen HR, Collen D. A monoclonal antibody specific for lys-plasminogen: application to the study of activation pathways of plasminogen in vivo. Journal of Biological Chemistry 260: 12106–12111, 1985

    PubMed  CAS  Google Scholar 

  • Husain SS, Gurewich V, Lipinski B. Purification and partial characterization of a single-chain high-molecular-weight form of urokinase from human urine. Archives of Biochemistry and Biophysics 220: 31–38, 1983

    Article  PubMed  CAS  Google Scholar 

  • ISAM Study Group. A prospective trial of intravenous streptokinase in acute myocardial infarction (ISAM): mortality, morbidity, and infarct size at 21 days. New England Journal of Medicine 314: 1465–1471, 1986

    Article  Google Scholar 

  • ISIS Collaborative Study Group. ISIS-2. Randomized trial of intravenous streptokinase, oral aspirin, both, or neither among 17,187 cases of suspected acute myocardial infarction: 1S1S-2. Second International Study of Infarct Survival Collaborative Group. Lancet 2: 349–360, 1988

    Google Scholar 

  • Jang I-K, van Haecke J, de Geest H. Coronary thrombolysis with recombinant tissue-type plasminogen activator: patency rate and regional wall motion after 3 months. Journal of the American College of Cardiology 8: 1455–1460, 1986

    Article  PubMed  CAS  Google Scholar 

  • Kasper W, Mainertz T, Wollschlaeger H, Bonzel T, Wolff P, et al. Coronary thrombolysis during acute myocardial infarction by intravenous BRL26921, a new anisoylated plasminogen-streptokinase activator complex. American Journal of Cardiology 58: 418–421, 1986

    Article  PubMed  CAS  Google Scholar 

  • Kawano T, Morimoto K, Uemura Y. Urokinase inhibitor in human placenta. Nature 217: 253–254, 1968

    Article  PubMed  CAS  Google Scholar 

  • Kennedy JW, Ritchie JL, Davis KB, Fritz JK. Western Washington randomized trial of intracoronary streptokinase in acute myocardial infarction. New England Journal of Medicine 309: 1477–1482, 1983

    Article  PubMed  CAS  Google Scholar 

  • Kennedy JW, Ritchie JL, Davis KB, Stadius ML, Maynard C, et al. The Western Washington randomized trial of intracoronary streptokinase in acute myocardial infarction: a 12-month follow-up report. New England Journal of Medicine 312: 1073–1078, 1985

    Article  PubMed  CAS  Google Scholar 

  • Kosow DP. Kinetic mechanism of the activation of human plasminogen by streptokinase. Biochemistry 14: 4459–4465, 1975

    Article  PubMed  CAS  Google Scholar 

  • Loscalzo J. A structural and kinetic comparison of recombinant human single-chain and two-chain tissue plasminogen activator. Journal of Clinical Investigation, 82: 1391–1397, 1988

    Article  PubMed  CAS  Google Scholar 

  • Loscalzo J, Vaughan DE. Human tissue-type plasminogen activator facilitates platelet disaggregation. Journal of Clinical Investigation 79: 1749–1755, 1987

    Article  PubMed  CAS  Google Scholar 

  • Loscalzo J, Wharton TP, Kirshenbaum JM, Levine HJ, Flaherty JT, et al., for the Prourokinase in Myocardial Infarction Study Group. The efficacy and fibrin specificity of prourokinase in acute myocardial infarction. Circulation, in press 1989

  • Mickelson JK, Simpson PJ, Gallas MT, Lucchesi BR. Thromboxane synthetase inhibition with CGS 13080 improves coronary blood flow after streptokinase-induced thrombolysis. American Heart Journal 113: 1345–1352, 1987

    Article  PubMed  CAS  Google Scholar 

  • Monk JP, Heel RC. Anisoylated plasminogen streptokinase activator complex (APSAC). A review of its mechanism of action, clinical pharmacology and therapeutic use in acute myocardial infarction. Drugs 34: 25–49, 1987

    CAS  Google Scholar 

  • Mueller HS, Rao AK, Forman MA, for the TIMI investigators. Thrombolysis in myocardial infarction (TIMI): comparative studies of coronary reperfusion and systemic fibrinogenolysis with two forms of recombinant tissue-type plasminogen activator. Journal of the American College of Cardiology 10: 479–490, 1987

    Article  PubMed  CAS  Google Scholar 

  • Nelles L, Lijnen HR, Collen D, Holmes WE. Characterization of recombinant human single chain urokinase-type plasminogen activator mutants produced by site-specific mutagenesis of lysine 158. Journal of Biological Chemistry 262: 5682–5689, 1987

    PubMed  CAS  Google Scholar 

  • Nicklas JM, Topol EJ, Kander N, Walton JA, Gorman L, et al. Randomized, double-blind, placebo-controlled trial of rt-PA in unstable angina. Circulation 76: IV–305, 1987

    Google Scholar 

  • Niewiarowski S, Senyi AF, Gillies P. Plasmin-induced platelet aggregation and platelet release reaction. Journal of Clinical Investigation 52: 1647–1659, 1973

    Article  PubMed  CAS  Google Scholar 

  • Passamani E, Hodges M, Herman M, Grose R, Chaitman B, et al. The Thrombolysis in Myocardial Infarction (TIMI) phase II pilot study: tissue plasminogen activator followed by percutaneous transluminal coronary angioplasty. Journal of the American College of Cardiology 10: 51B-64B, 1987

    Article  Google Scholar 

  • Rao AK, Pratt B, Berke A, Jaffe A, Ockene I, et al. Thrombolysis in Myocardial Infarction (TIMI) Trial, Phase I: hemorrhagic manifestations and changes in plasma fibrinogen and the fibrinolytic system in patients treated with recombinant tissue plasminogen activator and streptokinase. Journal of the American College of Cardiology 11: 1–11, 1988

    Article  PubMed  CAS  Google Scholar 

  • Rentrop P, Blanke H, Karsch KR, Wiegand V, Kostering H, et al. Acute myocardial infarction: intracoronary application of nitroglycerine and streptokinase. Clinical Cardiology 2: 354–363, 1979

    PubMed  CAS  Google Scholar 

  • Rijken DC, Collen DC. Purification and characterization of the plasminogen activator secreted by human melanoma cells in culture. Journal of Biological Chemistry 256: 7035–7041, 1981

    PubMed  CAS  Google Scholar 

  • Rijken DC, Hoylaerts M, Collen D. Fibrinolytic properties of one-chain and two-chain human extrinsic (tissue type) plasminogen activator. Journal of Biological Chemistry 257: 2920–2925, 1982

    PubMed  CAS  Google Scholar 

  • Rijken DC, Juhan-Vague I, Collen D. Complexes between tissue-type plasminogen activator and proteinase inhibitors in human plasma, identified with an immunoradiometric assay. Journal of Laboratory and Clinical Medicine 101: 285–294, 1983

    PubMed  CAS  Google Scholar 

  • Rothbard DL, Fitzpatrick P, Francis CW, Caton DM, Hood Jr WB, et al. Relationship of the lytic state to successful reperfusion with standard- and low-dose intracoronary streptokinase. Circulation 71: 562–570, 1985

    Article  PubMed  CAS  Google Scholar 

  • Schafer AI, Adelman B. Plasmin inhibition of platelet function and of arachidonic acid metabolism. Journal of Clinical Investigation 75: 456–461, 1985

    Article  PubMed  CAS  Google Scholar 

  • Schafer AI, Maas AK, Ware JA, Johnson PC, Rittenhouse SE, et al. Platelet protein phosphorylation, elevation of cytosolic calcium, and inositol phospholipid breakdown in platelet activation induced by plasmin. Journal of Clinical Investigation 78: 73–79, 1986

    Article  PubMed  CAS  Google Scholar 

  • Sharma B, Wyeth RP, Gimenez HJ, Franciosa JA. Intracoronary prostaglandin E1 plus streptokinase in acute myocardial infarction. American Journal of Cardiology 58: 1161–1166, 1986

    Article  PubMed  CAS  Google Scholar 

  • Sharma B, Wyeth RP, Heinemann FA, Kolath G. Adjunctive use of intracoronary prostaglandin E1 with streptokinase enhances intracoronary thrombolysis. Circulation 76: IV–181, 1987

    Google Scholar 

  • Sherman CT, Litvack F, Grundfest W, Lee M, Hickey A, et al. Coronary angioscopy in patients with unstable angina pectoris. New England Journal of Medicine 315: 913–919, 1986

    Article  PubMed  CAS  Google Scholar 

  • Simoons ML, Serruys PW, Brand Bar F, de Zwaans C, et al. Improved survival after early thrombolysis in acute myocardial infarction: a randomized trial by the Interuniversity Cardiology Institute in the Netherlands. Lancet 2: 578–581, 1985

    Article  PubMed  CAS  Google Scholar 

  • Sobel BE, Saffitz JE, Fields LE, Myears DW, Sarnoff SJ, et al. Intramuscular administration of human tissue-type plasminogen activator in rabbits and dogs and its implications for coronary thrombolysis. Circulation 75: 1261–1272, 1986

    Article  Google Scholar 

  • Stampfer MJ, Goldhaber SZ, Yusuf MRCP, Peto R, Hennekens CH. Effects of intravenous streptokinase in acute myocardial infarction: pooled results from randomized trials. New England Journal of Medicine 307: 1180–1182, 1982

    Article  PubMed  CAS  Google Scholar 

  • Suenson E, Petersen LC. Fibrin and plasminogen structures essential to stimulation of plasmin formation by tissue-type plasminogen activator. Biochimica et Biophysica Acta 870: 510–519, 1986

    Article  PubMed  CAS  Google Scholar 

  • TIMI Study Group. The Thrombolysis in Myocardial Infarction (TIMI) Trial. New England Journal of Medicine 312: 932–936, 1985

    Google Scholar 

  • Topol EJ, Bates ER, Walton Jr JA, Baumann G, Wolfe S, et al. Community hospital administration of intravenous tissue plasminogen activator in acute myocardial infarction: improved timing, thrombolytic efficacy and ventricular function. Journal of the American College of Cardiology 10: 1173–1177, 1987a

    Article  PubMed  CAS  Google Scholar 

  • Topol EJ, Califf RM, George BS, Kereiakes DJ, Abbottsmith CW, et al. A randomized trial of immediate versus delayed elective angioplasty after intravenous tissue plasminogen activator in acute myocardial infarction. New England Journal of Medicine 317: 581–588, 1987b

    Article  PubMed  CAS  Google Scholar 

  • Topol EJ, Califf RM, Kereiakes DJ, George BS. Thrombolysis and angioplasty in myocardial infarction (TAMI) trial. Journal of the American College of Cardiology 10: 65B-74B, 1987c

    Article  Google Scholar 

  • Topol EJ, Morris DC, Smalling RW, Schumacher RR, Taylor CR, et al. A multicenter, randomized, placebo-controlled trial of a new form of intravenous recombinant tissue-type plasminogen activator (Activase) in acute myocardial infarction. Journal of the American College of Cardiology 9: 1205–1213, 1987d

    Article  PubMed  CAS  Google Scholar 

  • Van de Werf F, Nobuhara M, Collen D. Coronary thrombolysis with human single-chain urokinase-type plasminogen activator in patients with acute myocardial infarction. Annals of Internal Medicine 104: 345–348, 1986

    PubMed  Google Scholar 

  • Van Mourik JA, Lawrence DA, Loskutoff DJ. Purification of an inhibitor of plasminogen activator (antiactivator) synthesized by endothelial cells. Journal of Biological Chemistry 259: 14914–14921, 1984

    PubMed  Google Scholar 

  • Van Zonneveld A-J, Veerman H, Pannekoek H. Autonomous functions of structural domains on human tissue-type plasminogen activator. Proceedings of the National Academy of Sciences (USA) 83: 4670–4674, 1986

    Article  Google Scholar 

  • Vaughan DE, Goldhaber SZ, Kim J, Loscalzo J. Recombinant tissue plasminogen activator in acute pulmonary embolism: quantitation of fibrinolytic specificity and hematologic determinants of efficacy. Circulation 75: 1200–1203, 1987

    Article  PubMed  CAS  Google Scholar 

  • Vaughan DE, Plavin SR, Schafer AI, Loscalzo J. Prostaglandin E1 markedly accelerates thrombolysis by tissue plasminogen activator. Blood, in press, 1989

  • Verstraete M. Intravenous administration of thrombolytic agents is the only realistic approach in evolving myocardial infarction. European Heart Journal 6: 568–573, 1985

    Google Scholar 

  • Verstraete M, Arnold AER, Brower RW, Collen D, de Bono DP, et al. Acute coronary thrombolysis with recombinant human tissue-type plasminogen activator: initial patency and influence of maintained infusion on reocclusion rate. American Journal of Cardiology 60: 231–237, 1987

    Article  PubMed  CAS  Google Scholar 

  • Verstraete M, Bernard R, Bory M, Brower RW, Collen D, et al. Randomised trial of intravenous recombinant tissue-type plasminogen activator versus intravenous streptokinase in acute myocardial infarction. Lancet 1: 842–847, 1985

    Article  PubMed  CAS  Google Scholar 

  • Wallen P, Wiman B. Characterization of human plasminogen. II. Separation and partial characterization of different forms of human plasminogen. Biochimica et Biophysica Acta 257: 122–131, 1972

    Article  PubMed  CAS  Google Scholar 

  • White HD, Norris RM, Brown MA, Takayama M, Maslowski A, et al. Effect of intravenous streptokinase on left ventricular function and early survival after acute myocardial infarction. New England Journal of Medicine 317: 850–856, 1987

    Article  PubMed  CAS  Google Scholar 

  • Wilcox RG, von der Lippe G, Olsson CG, Jensen G, Skene AM, et al. for the ASSET Study Group. Trial of tissue plasminogen activator for mortality reduction in acute myocardial infarction: Anglo-Scandinavian Study of Early Thrombolysis (ASSET). Lancet 2: 525–530, 1988

    Article  PubMed  CAS  Google Scholar 

  • Yusuf S, Collins R, Peto R, Furberg C, Stampfer MJ, et al. Intravenous and intracoronary fibrinolytic therapy in acute myocardial infarction: overview of results on mortality, reinfarction, and side-effects from 33 randomized controlled trials. European Heart Journal 6: 556–585, 1985

    PubMed  CAS  Google Scholar 

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Loscalzo, J. Thrombolysis in the Management of Acute Myocardial Infarction and Unstable Angina Pectoris. Drugs 37, 191–204 (1989). https://doi.org/10.2165/00003495-198937020-00006

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