Skip to main content
SpringerLink
Log in

Effects of Trimetazidine Administration before Thrombolysis in Patients with Anterior Myocardial Infarction: Short-term and Long-term Results

  • Published:
Cardiovascular Drugs and Therapy Aims and scope Submit manuscript

Abstract

Reperfusion may prevent or reduce the development and extent of necrosis, but may also lead to an increase in reperfusion damage. Experimental studies performed in various animal models of myocardial ischemia have demonstrated the anti-ischemic properties of trimetazidine (TMZ) and have suggested that TMZ has antioxidant properties, without any direct hemodynamic effects. Our study was aimed at investigating the effects of TMZ before thrombolysis in acute anterior myocardial infarction and included 81 patients, hospitalized within 4 hours of the onset of symptoms. Patients were randomly (double-blind) subdivided in two groups The first group (40 patients, Group A, TMZ-pretreatment), received 40 mg TMZ orally about 15 minute before thrombolysis and, subsequently, 20 mg every 8 hours. The second group (41 patients, Group B) received placebo before thrombolysis. Ventricular arrhythmias (VA) due to reperfusion were evaluated in the first 2 hours. VA occurred in 15 of patients in group A, versus 29 in group B, p < 0.05. Creatine kinase (CK) normalization time was achieved after 55.7 ± 12.5 hours in group A, versus 61.2 ± 12.1 hour in group B, p = 0.048. CK peak was 1772 ± 890 in group A vs 2285 ± 910 UI/1 in group B, (p = 0.012). In the follow-up (range 6–22 months), there were 4 deaths, two patients in each group. After 180 days from treatment, the TMZ group showed a smaller end systolic volume than the placebo group (echocardiographic data), 46.2 ± 12 and 52.8 ± 13 ml/m2, respectively, p = 0.037. Our data suggest that TMZ probably reduces reperfusion damage and/or infarct size in patients with anterior AMI subjected to thrombolysis and affects the post-AMI remodeling. Our data must be interpreted with caution because of the selection of patients. These findings require further extensive trials.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Ambrosio G, Welsfeldt ML, Jacobus WE, Flaherty JT. Evidence for a reversible oxygen radical-mediated component of reperfusion injury: Reduction by recombinant superoxide dismutase administered at the time of reflow. Circulation 1987;75:282–291.

    Google Scholar 

  2. Burton KP, Evidence of direct toxic effects of free radicals on the myocardium. Free Rad Biol Med 1988;4:15–24.

    Google Scholar 

  3. Jennings RB, Reimer KA. Factors involved in salvaging ischemic myocardium. Effects of reperfusion of arterial blood. Circulation 1983;68(Suppl):I-25–I-36.

    Google Scholar 

  4. Becker LC, Ambrosio G. Myocardial consequences of reperfusion. Prog Cardiovasc Dis 1987;30:23–44.

    Google Scholar 

  5. Harpey C, Clauser P, Labrid C, Freyria H, Poirier JP. Trimetazidine, a cellular anti-ischemic agent. Cardiovasc Drug Rev 1988;6:292–312.

    Google Scholar 

  6. Belcher P, Drake-Holland AJ, Hynd JW, Noble MIM. Trimetazidine reduces myocardial infarct size, relative area at risk, after temporary artery occlusion in the rabbit. Br J Pharmacol 1992;107:265P.

    Google Scholar 

  7. Drake-Holland AJ, Belcher PR, Hynd JW, Noble IM. Infarct size in rabbits: A modified illustrated by the effects of propanolol and trimetazidine. Basic Res Cardiol 1993;88:250–258.

    Google Scholar 

  8. Takenada F, Sakaniski M, Watanabe A. Effects of trimetazidine in the coronary circulation and myocardial metabolism in the dog. Pharmacometrics 1976;11:429–435.

    Google Scholar 

  9. Fabiani JN, Ponzio O, Emerit I, Massonet-Castel S, Paris M, Chevaller P, Jebara B, Carpentier A. Cardioprotective effects of trimetazidine during coronary artery graft surgery. J Cardiovasc Surg 1992;33:486–490.

    Google Scholar 

  10. Kober G, Buck T, Severt H, Vallbracht C. Myocardial protection during percutaneous transluminal coronary angioplasty: Effects of trimetazidine. Eur Heart J 1992;13:1109–1115.

    Google Scholar 

  11. Di Pasquale P, Bucca V, Giuliano P, Maringhini G, Scalzo S, Paterna S. Advantages of immediate two-dimensional echocardiography in patients with acute cardiac ischemic events. Int J Cardiol 1995;51:85–91.

    Google Scholar 

  12. Honore E, Adamantidis MM, Challice CE, Dupuis BA. Cardioprotection by calcium antagonist, piridoxilate and trimetazidine. RCS Med Sci 1986;14:338–339.

    Google Scholar 

  13. Lavanchy N, Martin J, Rossi A. Anti-ischemic effects of trimetazidinc: P-NMR spectroscopy in the isolated rat heart. Arch Int Pharmacodyn Ther 1987;286:97–110.

    Google Scholar 

  14. Bricaud H, Brottier I, Barat JH, Combe C, Broussens B, Bonnet J. Cardioprotective effect of trimetazidine in severe ischemic cardiomyopathy. Cardiovasc Drug Ther 1990;4:861–865.

    Google Scholar 

  15. Fantini E, Demaison L, Sentex E, Grynberg A, Athias P. Some biochemical aspects of the protective effect of trimetazidine on rat cardiomyocytes during hypoxia and reoxygenation. J Mol Cell Cardiol 1994;26:949–958.

    Google Scholar 

  16. Cruz C, Zaoui A, Ayoub S, Harpey C, Goupil P, Younes A. Alterations des myocytes isole' des ventricules de coeur de rat adulte: Protection par la Trimetazidine Concours Medicale. 1987;36(Suppl 34):70–75.

    Google Scholar 

  17. Nagata M, Imamura I, Fugono R, Sugimoto J. The actions of trimetazidine on isolated guinea-pig atria. Jpn J Pharmacol 1971;21:337–343.

    Google Scholar 

  18. Renaud JF. Intemal pH, Na+ and Ca++ regulation by trimetazidine during cardiac cell necrosis. Cardiovasc Drug Ther 1988;1:677–686.

    Google Scholar 

  19. Mardonneau-Parini I, Harpey C. Effects of trimetazidine on membrane damage induced by oxygen free radicals in human red cells. Br J Clin Pharmacol 1985;20:148–151.

    Google Scholar 

  20. Clauser P, Harpey C. Anti-oxidant properties of an anti-ischemic agent. Trimetazidine. In: Emerit J, Packer L, Auclair C, eds. Antioxidants in Therapy and Preventive Medicine. New York: Plenum Press, 1990: 247–250.

    Google Scholar 

  21. Rahman F, Toshiba Y, Kohno H, Kinoshita K, Tokunaga K. The protective effects of trimetazidine on normothermic ischemic myocardium in rats. Jpn J Surg 1989;19:346–350.

    Google Scholar 

  22. Guamieri C, Muscari C. Effect of trimetazidine on mithocondrial function and oxidative damage during reperfusion of ischemic hypertrophied rat myocardium. Pharmacology 1993;46:324–331.

    Google Scholar 

  23. Guamieri C. How can cardiac mitochondrial metabolism be manipulated? Dialogues Cardiovasc Med 1996;1:89–92.

    Google Scholar 

  24. Kay L, Finelli C, Aussedat J, Guarnieri C, Rossi A. Improvement of long-term preservation of the isolated rat heart by trimetazidine: Effects on the energy state and mitochondrial function. Am J Cardiol 1995;76:45B–49B.

    Google Scholar 

  25. de Leiris J, Bouder F. Rationale for trimetazidine administration in myocardial ischemia reperfusion syndrome. Eur Heart J 1993;14(Suppl G):34–40.

    Google Scholar 

  26. Manning AS, Hearse DJ. Reperfusion-induced arrhythmias: Mechanisms and prevention. J Mol Cell Cardiol 1984;16:497–518.

    Google Scholar 

  27. Maupoil V, Rochette L, Tabard A, Clauser P, Arpey C. Direct measurements of the free radical generation in isolated rat heart by electron paramagnetic resonance spectroscopy: Effect of Trimetazidine. In: Emerit I, Packer L, Auclair C, eds. Antioxidants in Therapy and Preventive Medicine. Adv Exp Ed Biol 1990;264:373–376.

  28. Charlene V, Boucher F, Closer P, et al. Effect of a 5 day trimetazidine pretreatment in a model of ischemic and reperfused isolated rat heart: spin trapping experiments. In: Emerit I, Pecker L, Auclair C, eds. Antioxidants in Therapy and Preventive Medicine. Adv Exp Med Biol 1990;264:377–382.

  29. Williams FM, Tanda K, Kas M, Williams TJ. Inhibition of neutrophil accumulation into ischemic reperfused myocardium in the rabbit by trimetazidine. J Mol Cell Cardiol 1992;24(Suppl 1):S90.

    Google Scholar 

  30. Camilleri JP, Joseph D. Effects de la trimetazidine sur I'infarctus experimental du rat reperfusé. Arch Mal Coeur Vaisseaux 1988;81:371–376.

    Google Scholar 

  31. Sellier P, Audoin P, Rayen B, Corona P, Duong TC, Ourbak P. Acute effects of trimetazidine evaluated by exercise testing. Eur J Clin Pharmacol 1987;33:205–207.

    Google Scholar 

  32. Dalla Volta S, Maraglino G, Della Valentina P, Desideri A. Comparison of trimetazidine with nifedipine in effort angina: a double blind cross-over study. Cardiovasc Drug Ther 1990;4:853–860.

    Google Scholar 

  33. Lu C, Dabrowski P, Fragasso G, Chierca S. Effects of trimetazidine on ischemic left ventricular dysfunction in patients with coronary artery disease: A randomized double-blind placebo-controlled, crossover study (Abstract). Circulation 1997;96(Suppl):I-91

    Google Scholar 

  34. Detry JM, Sellier P, Pennaforte S, Cokkinos D, Dargie H, Mathes P. Trimetazidine a new concept in the treatment of angina. Comparison with propanolol in patients with stable angina. Br J Clin Pharmacol 1994;37:279–288.

    Google Scholar 

  35. Brottier L, Barat 1, Combe C, Boussens B, Bonnet J, Bricaud H. Therapeutic value of a cardioprotective agent in patients with severe ischaemic cardiomyopathy. Eur Heart J 1990;11:207–212.

    Google Scholar 

  36. EMIP-FR Pilot Study Group. Free radicals reperfusion and myocardial infarction therapy: European Myocardial Infarction Project-Free radical Pilot study EMIP-FR Pilot Study Group. Eur Heart J 1993;14(Suppl G):48–51.

    Google Scholar 

  37. Drobrusky G, Deroux A, Schutz D. Traitement de I'angor par Vastarel 20 mg en pratique medicale quotidienne. Vie Medicale 1985;9:441–448.

    Google Scholar 

  38. Guillaumet D, Scutz D. Vastarel 20 mg: efficacité et securité d'emploi en cardiologie chez 906 patients insuffisant coronariens. Tempo Med 1982;110:74–78.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Cardiology “Paolo Borsellino”, G. F. Ingrassia Hospital Palermo, Italy

    Pietro Di Pasquale, Pietro Lo Verso, Vincenzo Bucca, Sergio Cannizzaro, Sebastiano Scalzo, Giorgio Maringhini & Rosa Rizzo

  2. Department of Internal Medicine, University of Palermo, Italy

    Salvatore Paterna

Authors
  1. Pietro Di Pasquale
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Pietro Lo Verso
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Vincenzo Bucca
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Sergio Cannizzaro
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Sebastiano Scalzo
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Giorgio Maringhini
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Rosa Rizzo
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Salvatore Paterna
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Di Pasquale, P., Lo Verso, P., Bucca, V. et al. Effects of Trimetazidine Administration before Thrombolysis in Patients with Anterior Myocardial Infarction: Short-term and Long-term Results. Cardiovasc Drugs Ther 13, 423–428 (1999). https://doi.org/10.1023/A:1007804007115

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1007804007115

Search

Navigation