Skip Navigation

European Heart Journal 2001 22(24):2267-2274; doi:10.1053/euhj.2001.2896
Copyright © 2001 by the European Society of Cardiology.
This Article
Right arrow Abstract Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow E-letters: Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when E-letters are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Search for citing articles in:
ISI Web of Science (44)
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Szwed, H.
Right arrow Articles by Winter, M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Szwed, H.
Right arrow Articles by Winter, M.
Social Bookmarking
 Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Combination treatment in stable effort angina using trimetazidine and metoprolol. Results of a randomized, double-blind, multicentre study (TRIMPOL II)

H. Szweda,f1, Z. Sadowskia, W. Elikowskib, A. Koronkiewiczc, A. Mamcarzd, W. Orszulake, E. Skibinskaf, K. Szymczakg, J. Swiatekh and M. Winteri

a Department of Ischemic Heart Disease, National Institute of Cardiology, Warsaw, Poland
b II Department of Internal Disease, City Hospital, Poznan, Poland
c I Department of Internal Disease, City Hospital, PCK, Bialystok, Poland
d Department of Cardiology, Medical University of Warsaw, Warsaw, Poland
e I Department of Cardiology, Institute of Cardiology, Silesian School of Medicine, Katowice, Poland
f Department of Cardiology, Medical University of Bialystok, Bialystok, Poland
g Voivodship Cardiological Center, lomza, Poland
h Department of Cardiology, Voivodship Hospital, Siedlce, Poland
i Cardiologic Diagnostics and Rehabilitation Center, Wroclaw, Poland

revised July 13, 2001; accepted July 18, 2001

Abstract

Aims To assess the antiischaemic efficacy and tolerability of the metabolic agent trimetazidine in combination with metoprolol in patients with stable effort angina.

Methods This was a randomized, multicentre, double-blind, placebo-controlled parallel group study. A total of 426 male and female patients with stable, effortinduced angina and documented coronary artery disease received either placebo or trimetazidine 20mg three times daily in addition to metoprolol 50mg twice daily. Treadmill exercise tests were performed at weeks (–1), 0, 4 and 12.

Results After 12 weeks, there were significantly greater improvements in the metoprolol + trimetazidine group than in the metoprolol + placebo group in: time to 1mm ST segment depression, total workload, time to onset of angina, maximum ST segment depression, mean weekly number of angina attacks, mean weekly nitrate consumption, and grade of anginal pain. There was no evidence of any development of tolerance to trimetazidine. The tolerability of trimetazidine was excellent.

Conclusions Therapy with trimetazidine plus metoprolol produced significant improvements in exercise stress tests and the symptoms of angina relative to metoprolol alone. With its metabolic effect, devoid of any haemodynamic action, trimetazidine is useful for combination therapy in patients with stable angina insufficiently controlled by monotherapy with a beta-blocker.

Key Words: Stable angina, trimetazidine, metoprolol, combination therapy, metabolic agent, exercise testing

f1 Correspondence: Professor Hanna Szwed, National Institute of Cardiology, Ischemic Heart Disease Department, 1 Spartaska Street, 02-637 Warsaw, Poland.

References

  1. McClellan KJ, Plosker GL. Trimetazidine. A review of its use in stable angina pectoris and other coronary conditions. Drugs. 1999;58:143–157[CrossRef][Web of Science][Medline]
  2. Eur Heart J. 1997;18:394–413[Free Full Text]
  3. Packer M. Combined beta-adrenergic and calcium entry blockade in angina pectoris. N Engl J Med. 1989;320:709–718[Web of Science][Medline]
  4. Pepine CJ, Abrams J, Marks RG, Morris JJ, Scheidt SS, Handberg E. Characteristics of a contemporary population with angina pectoris. Am J Cardiol. 1994;74:226–231[CrossRef][Web of Science][Medline]
  5. Fox KM, Mulcahy D, Findlay I, Ford I, Dargie HJ. The Total Ischaemic Burden European Trial (TIBET). Effects of atenolol, nifedipine SR and their combination on the exercise test and total ischaemic burden in 608 patients with stable angina. Eur Heart J. 1996;17:96–103[Abstract/Free Full Text]
  6. Savonitto S, Ardissino D, Egstrup K. Combination therapy with metoprolol and nifedipine versus monotherapy in patients with stable angina pectoris. Results of the International Multicenter Angina Exercise (IMAGE) Study. J Am Coll Cardiol. 1996;27:311–316[Abstract]
  7. Knight C. From antianginal drugs to myocardial cytoprotective agents. Am J Cardiol. 1995;76:4B–7B[CrossRef][Medline]
  8. Stanley WC, Lopaschuk GD, Hall JL, McCormack. Regulation of myocardial carbohydrate metabolism under normal and ischaemic conditions. Potential for pharmacological interventions. Cardiovasc Res. 1997;33:243–257[Free Full Text]
  9. Kantor PF, Lucien A, Kozak R, Lopaschuk GD. The antianginal drug trimetazidine shifts cardiac energy metabolism from fatty acid oxidation to glucose oxidation by inhibiting mitochondrial long-chain 3-ketoacyl coenzyme A thiolase. Circ Res. 2000;86:580–588[Abstract/Free Full Text]
  10. El Banani H, Bernard M, Baetz D. Changed in intracellular sodium and pH during ischaemia-reperfusion are attenuated by trimetazidine. Comparison between low- and zero-flow ischaemia. Cardiovasc Res. 2000;47:688–696[Abstract/Free Full Text]
  11. Passeron J. Effectiveness of trimetazidine in stable effort angina due to chronic coronary insufficiency. A double-blind versus placebo study. Presse Med. 1986;15:1775–1778[Web of Science][Medline]
  12. Detry JM, Sellier P, Pennaforte S. Trimetazidine: a new concept in the treatment of angina. Comparison with propranolol in patients with stable angina. Br J Clin Pharmacol. 1994;37:279–288[Web of Science][Medline]
  13. Dalla-Volta S, Maraglino G, Della-Valentina P. Comparison of trimetazidine with nifedipine in effort angina: a double-blind, crossover study. Cardiovasc Drugs Ther. 1990;4:853–859
  14. Levy S. Combination therapy of trimetazidine with diltiazem in patients with coronary artery disease. Group of South of France Investigators. Am J Cardiol. 1995;76:12B–16B[CrossRef][Medline]
  15. Manchanda SC, Krishnasawami S. Combination treatment of trimetazidine and diltiazem in stable angina pectoris. Heart. 1997;78:353–357[Abstract/Free Full Text]
  16. Michaelides AP, Spiropoulos K, Dimopoulos K, Athanasiades D, Toutouzas P. Antianginal efficacy of the combination of trimetazidine–propranolol compared with isosorbide dinitrate–propranolol in patients with stable angina. Clin Drug Invest. 1997;13:8–14
  17. Szwed H, Pachocki R, Domzal-Bocheska M. Skuteczno i tolerancja trimetazydyny jako leku wiecowego u chorych z wysilkowa dusznica bolesna w skojarzeniu z jednym lekiem przeciwdlawicowym. Elektrofiz i Stym Serca. 1997;4:237–247
  18. Committee for Proprietary Medicinal Products (CPMP), Note for guidance on the clinical investigation of anti-anginal products in stable angina pectoris, London, European Agency for the Evaluation of Medicinal Products, 1996

Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
Am J Health Syst PharmHome page
K. Zerumsky and B. F. McBride
Ranolazine in the management of chronic stable angina
Am. J. Health Syst. Pharm., December 1, 2006; 63(23): 2331 - 2338.
[Abstract] [Full Text] [PDF]


Home page
Eur Heart J SupplHome page
P. G. Steg and D. Tchetche
Pharmacologic management of stable angina: role of ivabradine
Eur. Heart J. Suppl., September 1, 2006; 8(suppl_D): D16 - D23.
[Abstract] [Full Text] [PDF]


Home page
J CARDIOVASC PHARMACOL THERHome page
P. Parang, B. Singh, and R. Arora
Metabolic Modulators for Chronic Cardiac Ischemia
Journal of Cardiovascular Pharmacology and Therapeutics, October 1, 2005; 10(4): 217 - 223.
[Abstract] [PDF]


Home page
Eur Heart J SupplHome page
P. Gabriel Steg and D. Himbert
Unmet medical needs and therapeutic opportunities in stable angina
Eur. Heart J. Suppl., September 1, 2005; 7(suppl_H): H7 - H15.
[Abstract] [Full Text] [PDF]


Home page
Physiol. Rev.Home page
W. C. Stanley, F. A. Recchia, and G. D. Lopaschuk
Myocardial Substrate Metabolism in the Normal and Failing Heart
Physiol Rev, July 1, 2005; 85(3): 1093 - 1129.
[Abstract] [Full Text] [PDF]


Home page
Eur Heart JHome page
L. Lee, J. Horowitz, and M. Frenneaux
Metabolic manipulation in ischaemic heart disease, a novel approach to treatment
Eur. Heart J., April 2, 2004; 25(8): 634 - 641.
[Abstract] [Full Text] [PDF]


Home page
J CARDIOVASC PHARMACOL THERHome page
U. Thadani
Current Medical Management of Chronic Stable Angina
Journal of Cardiovascular Pharmacology and Therapeutics, March 1, 2004; 9(1_suppl): S11 - S29.
[Abstract] [PDF]


Home page
Circ. Res.Home page
G. D. Lopaschuk, R. Barr, P. D. Thomas, and J. R.B. Dyck
Beneficial Effects of Trimetazidine in Ex Vivo Working Ischemic Hearts Are Due to a Stimulation of Glucose Oxidation Secondary to Inhibition of Long-Chain 3-Ketoacyl Coenzyme A Thiolase
Circ. Res., August 8, 2003; 93 (3): e33 - e37.
[Abstract] [Full Text] [PDF]


Home page
SEMIN CARDIOTHORAC VASC ANESTHHome page
G. D. Lopaschuk and M. Marzilli
Mode of Action of Trimetazidine and Other New Metabolic Agents in the Treatment of Ischemic Heart Disease
Seminars in Cardiothoracic and Vascular Anesthesia, March 1, 2003; 7(1): 91 - 96.
[PDF]


Home page
Eur Heart JHome page
M. Frenneaux
New tricks for an old drug
Eur. Heart J., December 2, 2002; 23(24): 1898 - 1899.
[PDF]


Home page
CirculationHome page
R. Liao, M. Jain, L. Cui, J. D'Agostino, F. Aiello, I. Luptak, S. Ngoy, R. M. Mortensen, and R. Tian
Cardiac-Specific Overexpression of GLUT1 Prevents the Development of Heart Failure Attributable to Pressure Overload in Mice
Circulation, October 15, 2002; 106(16): 2125 - 2131.
[Abstract] [Full Text] [PDF]


Home page
Eur Heart JHome page
P. Meurin
Does 'more' mean maximal therapy
Eur. Heart J., September 2, 2002; 23(18): 1480 - 1480.
[Full Text] [PDF]


Home page
Eur Heart JHome page
C. Mannheimer and T. Eliasson
A reply
Eur. Heart J., September 2, 2002; 23(18): 1480 - 1480.
[Full Text] [PDF]


This Article
Right arrow Abstract Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow E-letters: Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when E-letters are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Search for citing articles in:
ISI Web of Science (44)
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Szwed, H.
Right arrow Articles by Winter, M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Szwed, H.
Right arrow Articles by Winter, M.
Social Bookmarking
 Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?