Comparing effectiveness of adding prolonged trimetazidine or isosorbide dinitrate to beta-adrenoblocker therapy in stable angina patients

Aim. To study effects of adding isosorbide dinitrate (ID) and trimetazidine MB 35 mg (Tr) to beta-adrenoblocker therapy in stable angina (SA) patients. Material and methods. In total, 40 patients with Functional Class II-III SA were examined. Combined therapy effectiveness was studied in a three-month randomized, open, comparative, parallel trial. Physical stress tolerance (PST) in treadmill test, angina attack incidence, nitrate dose, and health self-assessment dynamics (visual analogue scale) were assessed. Results. In both groups, PST increase by Month 1 was similar: 17% and 19%, respectively. Then PST stayed the same in ID group, and further increased in Tr group. By Month 3, PST in Tr group was twice as high as that in ID group: 15% and 34%, respectively. In Tr group, ST depression reduction, comparing to the baseline, was greater than in ID group: 49% vs 27%, respectively. It was associated with reduced angina attack incidence and need in short-acting nitrates. General health self-assessment improved by 20% (Month 1) and 35% (Month 3), comparing to 13% and 18% in ID group, respectively. Two participants dropped out of ID group, due to low medication tolerability (n=2), and myocardial infarction development (n=1). Conclusion. Comparing to ID, Tr demonstrated better tolerability profile, and long-run tolerance effect absence.

1. Lazar EJ, Frishman WH. Profile of an ideal antianginal agent. Drugs 1989; 38(Suppl 2): 1S-8.

2. ATP-survey. Российские данные из доклада Академика Оганова Р.Г. на Конгрессе кардиологов ВНОК 2003.

3. Manchanda SC, Krishnaswami S. Combination treatment with trimetazidine and diltiazem in stable angina pectoris. Heart 1997; 78: 353-7.

4. Akhras F, Jackson G. Efficacy of nifedipine and isosorbide mononitrate in combination with atenolol in stable angina. Lancet 1991; 338: 1036-9.

5. Марцевич С.Ю. Современные взгляды на терапию нитратами больных ишемической болезнью сердца. Сердце 2003; 2(2): 88-90.

6. Гиляревский С.Р. Применение нитратов при сердечно-сосудистых заболеваниях: границы доказанного и реальная практика. Cердце 2003; 3(3): 150-5.

7. Marzilli M. Trimetazidine: a metabolic agent for the treatment of stable angina. Eur Heart J 2001; 3(Suppl. O): O12-5.

8. Szwed H, Sadowski Z, Elikowski W, еt al. Combination treatment in stable effort angina using trimetazidine and metoprolol. Results of a randomized, double-blind, multicentre study (TRIMPOL II). Eur Heart J 2001; 22(24): 2267-74.

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(5): 580-8.

10. Петрий Н.Ю., Петрий В.В, Маколкин В.И. Оценка эффективности комбинации метопролола с триметазидином и изосорбида динитратом у больных со стабильной стенокардией с эпизодами безболевой ишемии миокарда в амбулаторных условиях. Кардиология 2001; 11: 11-3.

11. Chazov EI, Lepakchin VK,Zharova EA, et al. Trimetazidin in Angina Combination Therapy – TACT study: trimetazidine versus cjnventional treatment in patients with sta,le angina pectoris in a randomized, placebo-controlled, multicenter study Am J Ther 2005; 12(1): 35-42.

12. Hanania G, Haiat R, Olive T, et al. Coronary artery disease observed in general hospitals: ETTIC study. Comparison between trimetazidine and mononitrate isosorbide for patients receiving betablockers. Ann Cardiol Angeiol (Paris) 2002; 51(5): 268-74.

13. Selier P, Broustet JP. Assesment of Antiishemic and Antianginal Effect at Trough Plasma Concentration and Safety of Trimetazidine MR 35 mg in Patient with Stable Angina Pectoris. Cardiovasc Drugs 2003; 3: 361-9.

14. Michaelides AP, Spiropoulos K, Dimopoulos K, et al. Antianginal Efficacy of the combination of Trimetazidine-Propranolol Compared with Isosorbide Dinitrate-Propranolol in Patient with Stable Angina. Clin Drug Invest 1997; 13(1): 8-14.