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Thromb Haemost 1999; 82(S 01): 117-120
DOI: 10.1055/s-0037-1615567
Commentaries
Schattauer GmbH

TNK-tPA for Acute Myocardial Infarction: The Clinical Experience

Sorin V. Pislaru
1   From the Department of Cardiology, University of Leuven, Leuven, Belgium
,
Frans Van de Werf
1   From the Department of Cardiology, University of Leuven, Leuven, Belgium
› Author Affiliations
Further Information

Publication History

Publication Date:
14 December 2017 (online)

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Summary

Thrombolytic therapy has become the mainstay of treatment for acute transmural myocardial infarction. Present fibrinolytic regimens have a number of shortcomings, including the failure to induce early and sustained reperfusion in as many as 40-50% of the patients, and to prevent reocclusion in another 10-20% of the patients. The efforts for improving thrombolysis are focused on the development of new agents (fibrinolytics, anticoagulants, and antiplatelet agents). TNK-tPA is a triple combination mutant of wild-type tissue plasminogen activator that exhibits a longer plasma half-life, an enhanced fibrin-specificity, and an increased resistance to the plasminogen activator inhibitor-1. This paper summarizes the results of clinical trials with TNK-tPA in acute myocardial infarction.

Key words

Thrombolysis - TNK-tPA - acute myocardial infarction
 

  • References

  • 1 Van de Werf F, Califf RM, Armstrong PW, Bates ER, Ross AM, Kleinman NS, Topol EJ. on behalf of the GUSTO-I steering committee Progress culminating from ten years of clinical trials on thrombolysis for acute myocardial infarction. Eur Heart J 1995; 16: 1024-6.
    CrossrefPubMedGoogle Scholar
  • 2 Lincoff AM, Topol EJ. Illusion of reperfusion. Does anyone achieve optimal reperfusion during acute myocardial infarction? Circulation 1993; 88: 1361-74.
    PubMedGoogle Scholar
  • 3 Tanwell P, Tebbe U, Neuhaus K-L, Glasle-Schwarz L, Wojcik J, Seifried E. Pharmacokinetics and fibrin specificity of alteplase during accelerated infusions in acute myocardial infarction. J Am Coll Cardiol 1992; 19: 1071-5.
    CrossrefPubMedGoogle Scholar
  • 4 The GUSTO Investigators. An international randomized trial comparing four thrombolytic strategies for acute myocardial infarction. N Engl J Med 1993; 329: 673-82.
    CrossrefPubMedGoogle Scholar
  • 5 Kruithof EK, Tran-Thang C, Ransijn A, Bachmann F. Demonstration of a fast-acting inhibitor of plasminogen activators in human plasma. Blood 1984; 64: 907-13.
    PubMedGoogle Scholar
  • 6 Browne MJ, Carey JE, Chapman CG, Tyrrell AW, Entwisle C, Lawrence GM, Reavy B, Dodd I, Esmail A, Robinson JH. A tissue-type plasminogen activator mutant with prolonged clearance in vivo. Effect of removal of the growth factor domain. J Biol Chem 1988; 263: 1599-602.
    PubMedGoogle Scholar
  • 7 Hotchkiss A, Refino CJ, Leonard CK, O'Connor JV, Crowley C, McCabe J, Tate K, Nakamura G, Powers D, Levinson A, Mohler M, Spellman MW. The influence of carbohydrate structure on the clearance of recombinant tissue-type plasminogen activator. Thromb Haemost 1988; 60: 255-61.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 8 Madison EL, Goldsmith EJ, Gerard RD, Gething MJ, Sambrook JF, Bassel-Duby RS. Amino acid residues that affect interaction of tissue-type plasminogen activator with plasminogen activator inhibitor 1. Proc Natl Acad Sci USA 1990; 87: 3530-3.
    CrossrefPubMedGoogle Scholar
  • 9 Collen D, Lijnen HR, Gold HK. Towards better thrombolytic therapy. Prog Cardiovasc Dis 1991; 34: 101-12.
    CrossrefPubMedGoogle Scholar
  • 10 Bennett WF, Paoni NF, Keyt BA, Botstein D, Jones AJ, Presta L, Wurm FM, Zoller MJ. High resolution analysis of functional determinants on human tissue-type plasminogen activator. J Biol Chem 1991; 266: 5191-201.
    PubMedGoogle Scholar
  • 11 Keyt BA, Paoni NF, Refino CJ, Berleau L, Nguyen H, Chow A, Lai J, Pena L, Pater C, Ogez J, Etcheverry T, Botstein D, Bennett W. A faster-acting and more potent form of tissue plasminogen activator. Proc Natl Acad Sci USA 1994; 91 (9) 3670-4.
    CrossrefPubMedGoogle Scholar
  • 12 Benedict CR, Refino CJ, Keyt BA, Pakala R, Paoni NF, Thomas GR, Bennett WF. New variant of human tissue plasminogen activator (TPA) with enhanced efficacy and lower incidence of bleeding compared with recombinant human TPA. Circulation 1995; 92: 3032-40.
    CrossrefPubMedGoogle Scholar
  • 13 Collen D, Stassen JM, Yasuda T, Refino C, Paoni N, Keyt B, Roskams T, Guerrero JL, Lijnen HR, Gold HK, Bennett WF. Comparative thrombolytic properties of tissue-type plasminogen activator and of a plasminogen activator inhibitor-1-resistant glycosylation variant, in a combined arterial and venous thrombosis model in the dog. Thromb Haemost 1994; 72: 98-104.
    PubMedGoogle Scholar
  • 14 Cannon CP, McCabe CH, Gibson MC, Ghali M, Sequeira RF, McKendall GR, Breed J, Modi NB, Fox NL, Tracy RP, Love TW, Braunwald E. and the TIMI 10A Investigators TNK-tissue plasminogen activator in acute myocardial infarction. Results of the Thrombolysis in Myocardial Infarction (TIMI) 10A dose-ranging trial. Circulation 1997; 95: 351-6.
    PubMedGoogle Scholar
  • 15 Bovill EG, Terrin ML, Stump DC, Berke AD, Frederick M, Collen D, Feit F, Gore JM, Hillis LD, Lambrew CT, Leigoff R, Mann KG, Markis JE, Pratt CM, Sharkey SW, Sopko G, Tracy RP, Chesebro JH. for the TIMI Investigators 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: 256-65.
    PubMedGoogle Scholar
  • 16 Vanderschueren S, Barrios L, Kerdsinchai P, Van den Heuvel P, Hermans L, Vrolix M, De Man F, Benit E, Muyldermans L, Collen D, Van de, Werf F. for the STAR Trial Group A randomized trial of recombinant staphy-lokinase versus alteplase for coronary artery patency in acute myocardial infarction. Circulation 1995; 92: 2044-9.
    CrossrefPubMedGoogle Scholar
  • 17 Modi NB, Eppler S, Breed J, Cannon CP, Braunwald E, Love TW. Pharmacokinetics of a slower clearing tissue plasminogen activator variant, TNK-tPA, in patients with acute myocardial infarction. Thromb Haemost 1998; 79: 134-9.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 18 Cannon CP, McCabe CH, Gibson MC, Adgey JA, Sweiger MJ, Sequeira RF, Muller MS, McCluskey ER, Fox NL, Van de Werf F, Braunwald E. TNK-tissue plasminogen activator compared with front-loaded tissue plasminogen activator in acute myocardial infarction: primary results of the TIMI 10B trial. Circulation 1997; 96 (Suppl I) I-206 Abstract.
    PubMedGoogle Scholar
  • 19 Cannon CP, Gibson MC, McCabe CH, Adgey JAA, Schweiger MJ, Sequeira RF, Grollier G, Giugliano RP, Frey M, Mueller HS, Steingart RM, Weaver DW, Van de, Werf F, Braunwald E. for the TIMI 10B Investigators TNK-Tissue Plasminogen Activator compared with Front-loaded Alteplase in Acute Myocardial Infarction: Results of the TIMI 10B Trial. Circulation. 1998 In press.
    PubMedGoogle Scholar
  • 20 Giugliano RP, Cannon CP, McCabe CH, Van de Werf FJ, Braunwald E. Lower dose heparin with thrombolysis is associated with lower rates of intracranial hemorrhage: Results from TIMI 10B and ASSENT I. Circulation 1997; 96 (Suppl I) I-535 Abstract.
    PubMedGoogle Scholar
  • 21 Vorchheimer DA, Baruch L, Thompson TD, Kukin ML. North American vs. non-north American streptokinase use in GUSTO-I: Impact of protocol deviation on mortality benefit of TPA. Circulation 1997; 96 (Suppl I) I-535 Abstract.
    PubMedGoogle Scholar
  • 22 Gore JM, Granger CB, Simoons ML, Sloan MA, Weaver WD, White HD, Barbash GI, Van de Werf F, Aylward PE, Topol EJ, Califf RM, for the. GUSTO-I Investigators Stroke after thrombolysis: Mortality and functional outcomes in the GUSTO-I Trial. Circulation 1995; 92: 2811-8.
    CrossrefPubMedGoogle Scholar
  • 23 Simoons ML, Maggioni AP, Knatterud G, Leimgerger JD, de Jaegere R, van Domburg R, Boersma E, Franzosi MG, Schroder R, Braunwald E. Individual risk assessment for intracranial hemorrhage during thrombolytic therapy. Lancet 1993; 342: 1523-8.
    CrossrefPubMedGoogle Scholar
  • 24 Stangl K, Laule M, Tenckhoff B, Stangl V, Gliech V, Dubel P, Grohmann A, Melzer C, Langel J, Wernecke KD, Baumann G, Ziemer S. Fibrinogen breakdown, long-lasting systemic fibrinolysis, and procoagulant activation during alteplase double-bolus regimen in acute myocardial infarction. Am J Cardiol 1998; 81: 841-7.
    CrossrefPubMedGoogle Scholar
  • 25 The Continuous Infusion versus Double-bolus Administration of Alteplase (COBALT) Investigators. A comparison of continuous infusion of alteplase with double-bolus administration for acute myocardial infarction. N Engl J Med 1997; 337: 1124-30.
    CrossrefPubMedGoogle Scholar
  • 26 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: 329-36.
    CrossrefPubMedGoogle Scholar
  • 27 Lopez-Sendon JL. on behalf of the InTIME Investigators Intravenous nPA for Treatment of Infarction Myocardium Early: the InTIME study. Eur Heart J 1997; 18 (Suppl) 454 Abstract.
    PubMedGoogle Scholar
  • 28 Vanderschueren S, Dens J, Kerdsinchai P. et al. Randomized coronary patency trial of double-bolus recombinant staphylokinase versus front-loaded alteplase in acute myocardial infarction. Am Heart J 1997; 134: 213-9.
    CrossrefPubMedGoogle Scholar