Trimetazidine: a new metabolic approach in angina.
Effective and safe, even in polymedicated patients and those with concomitant disease

Dr Pierre Sabouret
Department of Cardiology, Hôpital Pitié-Salpétrière, Paris, France

In line with current enthusiasm for the metabolic approach to improving the treatment of ischemic heart disease, the use of trimetazidine has been endorsed in the latest recommendations of the task force of the European Society of Cardiology[1] (Table 1) and of the American College of Cardiology/American Heart Association[2] (Table 2). This follows recent publications on its efficacy and safety, in monotherapy or combination therapy, in ischemic heart disease. Furthermore, growing interest has been aroused as to how trimetazidine’s mechanism of action could explain its efficacy and acceptability.

Despite the extensive progress that has been made in its prevention and treatment during recent decades, ischemic heart disease is the primary cause of mortality worldwide today. It is expected to become the world’s leading cause of disease burden (which represents aggregate mortality and morbidity) by 2020.
Faced with this worrying perspective, the metabolic approach has been developed to provide new therapeutic solutions to improve on the unsatisfactory efficacy and tolerability of classic hemodynamic antianginal drugs.

A newly identified mode of action
Trimetazidine has been shown to modify energy metabolism in the heart. This mode of action has been recently determined by Kantor et al.,[3] who demonstrated that the antianginal effects of this metabolic agent may occur because of the inhibition of a mitochondrial enzyme: long-chain 3-ketoacyl-CoA-thiolase, which results in a reduction of fatty acid oxidation and a stimulation of glucose oxidation (Figure 1). Previous randomized clinical studies have shown that inhibition of fatty acid oxidation, combined with stimulation of glucose oxidation, can protect the ischemic heart.

Figure 1. Mode of action of trimetazidine. PDH, pyruvate dehydrogenase; ß-OX, beta-oxidation.

Evidence-based medicine: clinical data on trimetazidine
The growing interest in metabolic agents in the treatment of angina pectoris is due to the results of clinical studies with trimetazidine, which has been proven to be an effective antianginal agent.

Trimetazidine in monotherapy
In several double-blind trials, trimetazidine significantly improved the ergometric capacity and total work output of patients with effort angina,[4,5] reduced the frequency of attacks and nitroglycerin requirements in patients with chronic stable angina,[6] and increased their effort tolerance.[7] A European collaborative working group has demonstrated that the antianginal efficacy of trimetazidine is comparable to that of a beta-blocker (propranolol) but without reducing the heart rate-pressure product nor the coronary blood flow[8] (Figure 2). The absence of alteration of hemodynamic parameters to the same extent as nifedipine confers trimetazidine with an attractive safety profile.[9]

Figure 2. Effect of trimetazidine on time to onset of angina in comparison with propranolol. NS, not significant.

Trimetazidine: a suitable choice for combination therapy
In combination, trimetazidine provides additive benefits with beta-blockers or diltiazem, and superior efficacy to isosorbide dinitrate, without adding any side effects.[10–13]
The efficacy and safety of trimetazidine have also been confirmed in at-risk patients.

Trimetazidine in at-risk populations
Trimetazidine delayed the ischemic threshold in patients with left ventricular dysfunction and coronary artery disease on stress echocardiography.[14] In diabetic patients, trimetazidine significantly improved clinical symptoms, exercise duration, time to onset of angina, and time to 1 mm ST-segment depression. The tolerability of trimetazidine in this polymedicated population was assessed as good or excellent in 98% of patients[15].
In a recent study, the same beneficial effects, with remarkable safety, were extended to an elderly population.[16]

Conclusion
The management and treatment of ischemic heart disease remains a challenge. The angina population is aging, the percentage of hypertensive patients is high and the number of diabetic patients is increasing dramatically; epidemiological studies have revealed that the quality of life of the angina population is fair or poor (Figure 3).[17]

Figure 3. Quality of life of an outpatient cohort with chronic stable angina pectoris.[17]

 

Recently published studies on trimetazidine provide a cluster of evidence about the efficacy, safety and good quality of life achieved with this new metabolic agent.
Further studies are needed to detail the role of this promising metabolic approach to cardiovascular disease. 




REFERENCES
1. Wood D, De Backer G, Faergeman O et al., and other members of the Task Force. Prevention of coronary heart disease in clinical practice: recommendations of the Second Joint Task Force of European and other Societies on Coronary Prevention. Eur Heart J 1998; 19: 1434–1503.

2: J Am Coll Cardiol 1999 Jun;33(7):2092-197

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Erratum in:

• J Am Coll Cardiol 1999 Jul;34(1):314
• J Am Coll Cardiol 2001 Jul;38(1):296

 
ACC/AHA/ACP-ASIM guidelines for the management of patients with chronic stable angina: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on Management of Patients With Chronic Stable Angina).

Gibbons RJ, Chatterjee K, Daley J, Douglas JS, Fihn SD, Gardin JM, Grunwald MA, Levy D, Lytle BW, O'Rourke RA, Schafer WP, Williams SV, Ritchie JL, Cheitlin MD, Eagle KA, Gardner TJ, Garson A Jr, Russell RO, Ryan TJ, Smith SC Jr.

Publication Types:

• Guideline
• Practice Guideline

PMID: 10362225 [PubMed - indexed for MEDLINE]

3: Circ Res 2000 Mar 17;86(5):580-8

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Comment in:

• Circ Res. 2000 Mar 17;86(5):487-9.

 
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.

Kantor PF, Lucien A, Kozak R, Lopaschuk GD.

Cardiovascular Research Group and the Division of Pediatric Cardiology, University of Alberta, Edmonton, Canada.

Trimetazidine is a clinically effective antianginal agent that has no negative inotropic or vasodilator properties. Although it is thought to have direct cytoprotective actions on the myocardium, the mechanism(s) by which this occurs is as yet undefined. In this study, we determined what effects trimetazidine has on both fatty acid and glucose metabolism in isolated working rat hearts and on the activities of various enzymes involved in fatty acid oxidation. Hearts were perfused with Krebs-Henseleit solution containing 100 microU/mL insulin, 3% albumin, 5 mmol/L glucose, and fatty acids of different chain lengths. Both glucose and fatty acids were appropriately radiolabeled with either (3)H or (14)C for measurement of glycolysis, glucose oxidation, and fatty acid oxidation. Trimetazidine had no effect on myocardial oxygen consumption or cardiac work under any aerobic perfusion condition used. In hearts perfused with 5 mmol/L glucose and 0.4 mmol/L palmitate, trimetazidine decreased the rate of palmitate oxidation from 488+/-24 to 408+/-15 nmol x g dry weight(-1) x minute(-1) (P<0.05), whereas it increased rates of glucose oxidation from 1889+/-119 to 2378+/-166 nmol x g dry weight(-1) x minute(-1) (P<0.05). In hearts subjected to low-flow ischemia, trimetazidine resulted in a 210% increase in glucose oxidation rates. In both aerobic and ischemic hearts, glycolytic rates were unaltered by trimetazidine. The effects of trimetazidine on glucose oxidation were accompanied by a 37% increase in the active form of pyruvate dehydrogenase, the rate-limiting enzyme for glucose oxidation. No effect of trimetazidine was observed on glycolysis, glucose oxidation, fatty acid oxidation, or active pyruvate dehydrogenase when palmitate was substituted with 0.8 mmol/L octanoate or 1.6 mmol/L butyrate, suggesting that trimetazidine directly inhibits long-chain fatty acid oxidation. This reduction in fatty acid oxidation was accompanied by a significant decrease in the activity of the long-chain isoform of the last enzyme involved in fatty acid beta-oxidation, 3-ketoacyl coenzyme A (CoA) thiolase activity (IC(50) of 75 nmol/L). In contrast, concentrations of trimetazidine in excess of 10 and 100 micromol/L were needed to inhibit the medium- and short-chain forms of 3-ketoacyl CoA thiolase, respectively. Previous studies have shown that inhibition of fatty acid oxidation and stimulation of glucose oxidation can protect the ischemic heart. Therefore, our data suggest that the antianginal effects of trimetazidine may occur because of an inhibition of long-chain 3-ketoacyl CoA thiolase activity, which results in a reduction in fatty acid oxidation and a stimulation of glucose oxidation.

PMID: 10720420 [PubMed - indexed for MEDLINE]

4: Arch Mal Coeur Vaiss 1986 Aug;79(9):1331-6

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[The effects of trimetazidine on ergometric parameters in exercise-induced angina. Controlled multicenter double blind versus placebo study]

[Article in French]

Sellier P.

The antianginal effect of trimetazidine was assessed by a controlled multicentre double-blind versus placebo trial. The study included 32 males, average age 59.5 years, with stable angina of effort. The stability of angina was determined by two exercise stress tests performed at the beginning and at the end of a 15 day pre-selection period under placebo. The patients included in the trial were given 3 tablets a day of either trimetazidine (20 mg per tablet) or of placebo for one month. At the end of the treatment period the patients underwent a third exercise stress test. Comparing the results of exercise testing before and after treatment by a Mann and Whitney test, a statistically significant improvement with trimetazidine was demonstrated with respect to placebo for three parameters: total work increased from 4200 +/- 372 to 5620 +/- 387 Kpm in the trimetazidine group compared to 4191 +/- 399 to 4564 +/- 431 Kpm for placebo (p = 0.012); the duration of exercise increased from 10.2 +/- 0.5 to 12.1 +/- 0.5 minutes with trimetazidine compared to 10.2 +/- 0.5 to 10.7 +/- 0.5 with placebo (p = 0.016); the period to 1 mm ST depression increased from 8.3 +/- 0.6 to 9.8 +/- 0.5 minutes with trimetazidine compared to 8.4 +/- 0.5 to 9.0 +/- 0.7 minutes with placebo (p = 0.034). These results show that signs of ischaemia are delayed by trimetazidine. There were no significant changes in peripheral haemodynamics at rest or on effort. The antianginal action of trimetazidine seems therefore to be unrelated to a chronotropic or vasomotor effect and could be related to a mechanism of cellular regulation.

Publication Types:

• Clinical Trial
• Controlled Clinical Trial

PMID: 3101636 [PubMed - indexed for MEDLINE]

5: Presse Med 1986 Oct 16;15(35):1771-4

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[Ergometric effects of a single administration of trimetazidine]

[Article in French]

Sellier P, Audouin P, Payen B, Duong TC, Ourbak P.

The effects on exercise capacity of a single oral dose of 60 mg of trimetazidine were studied during a double-blind, placebo controlled cross-over study. Ten patients with stable angina and angiographically proven coronary artery lesions underwent ergometric bicycle exercise tests before and two hours after administration of the drug. A blood sample, for trimetazidine levels, was taken at the end of the recovery period. The homogeneity of the group and the lack of significance of the order of administration were established by cross-over analysis of the "control" tests and the "treated" tests. As compared with placebo, a statistically significant difference was noted after trimetazidine in the following parameters: total work (+31%, P less than 0.02), duration of exercise (+17%, P less than 0.02), percentage of the predicted maximal heart rate reached (+4%, P = 0.05), time to 1 mm ST segment depression (+17%, P less than 0.05) and degree of ST depression at maximum exercise level of the first control test (-31%, P less than 0.05); there was no significant difference in heart rate, blood pressure at rest and rate-pressure product during exercise between treatment and placebo. Two patients showed no response to trimetazidine. In the eight patients who did respond, there was a correlation factor of 0.73 between the plasma levels of trimetazidine and the increase in work performed. In conclusion, a single 60 mg dose of trimetazidine improves exercise tolerance and delays the ischaemic threshold during exercise without any detectable peripheral haemodynamic effects.

Publication Types:

• Clinical Trial
• Controlled Clinical Trial
• Randomized Controlled Trial

PMID: 2947148 [PubMed - indexed for MEDLINE]

6: Presse Med 1986 Oct 16;15(35):1775-8

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[Effectiveness of trimetazidine in stable effort angina due to chronic coronary insufficiency. A double-blind versus placebo study]

[Article in French]

Passeron J.

The antianginal activity of trimetazidine (Vastarel 20 mg) was evaluated in a double blind study versus placebo. The 54 subjects of the survey were males, of mean age 55.2 +/- 1.4 years in the trimetazidine group and 55.5 +/- 1.8 years in the placebo group, suffering from stable angina. The stability of angina was tested by two exercise tests carried out at the beginning and at the end of a two-week preselection period under placebo. Three tablets daily of either trimetazidine or placebo were given at random for two weeks. At the end of that time, a third exercise test was carried out. The clinical results showed a significant reduction (P less than 0.001) in the number of weekly attacks from 8.1 +/- 0.3 to 2.9 +/- 0.5 under trimetazidine and from 7.6 +/- 0.2 to 4.9 +/- 0.5 under placebo. Moreover, nitroglycerin consumption over a week decreased from 9.1 +/- 0.6 to 3.1 +/- 0.5 tablets under trimetazidine and from 7.9 +/- 0.3 to 5.4 +/- 0.6 tablets under placebo. The difference was significant (P less than 0.001). The global evaluation of the exercise tests showed a significant difference in favor of trimetazidine: 19 patients out of 27 improved under trimetazidine, as compared to 11 out of 27 under placebo. The total workload-capacity after treatment was increased by 62.1% under trimetazidine, and by 24.7% under placebo (P = 0.007). The rate-pressure product diminished by 12% with trimetazidine and by 4% with the placebo. Nevertheless, the interaction was not significant (P = 0.079). This study made it possible to evaluate the significant reduction of stress attacks frequency and nitroglycerin consumption under trimetazidine versus placebo. This clinical improvement was assessed by ergometric parameters.

Publication Types:

• Clinical Trial
• Randomized Controlled Trial

PMID: 2947149 [PubMed - indexed for MEDLINE]

7: Presse Med 1986 Oct 16;15(35):1775-8

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[Effectiveness of trimetazidine in stable effort angina due to chronic coronary insufficiency. A double-blind versus placebo study]

[Article in French]

Passeron J.

The antianginal activity of trimetazidine (Vastarel 20 mg) was evaluated in a double blind study versus placebo. The 54 subjects of the survey were males, of mean age 55.2 +/- 1.4 years in the trimetazidine group and 55.5 +/- 1.8 years in the placebo group, suffering from stable angina. The stability of angina was tested by two exercise tests carried out at the beginning and at the end of a two-week preselection period under placebo. Three tablets daily of either trimetazidine or placebo were given at random for two weeks. At the end of that time, a third exercise test was carried out. The clinical results showed a significant reduction (P less than 0.001) in the number of weekly attacks from 8.1 +/- 0.3 to 2.9 +/- 0.5 under trimetazidine and from 7.6 +/- 0.2 to 4.9 +/- 0.5 under placebo. Moreover, nitroglycerin consumption over a week decreased from 9.1 +/- 0.6 to 3.1 +/- 0.5 tablets under trimetazidine and from 7.9 +/- 0.3 to 5.4 +/- 0.6 tablets under placebo. The difference was significant (P less than 0.001). The global evaluation of the exercise tests showed a significant difference in favor of trimetazidine: 19 patients out of 27 improved under trimetazidine, as compared to 11 out of 27 under placebo. The total workload-capacity after treatment was increased by 62.1% under trimetazidine, and by 24.7% under placebo (P = 0.007). The rate-pressure product diminished by 12% with trimetazidine and by 4% with the placebo. Nevertheless, the interaction was not significant (P = 0.079). This study made it possible to evaluate the significant reduction of stress attacks frequency and nitroglycerin consumption under trimetazidine versus placebo. This clinical improvement was assessed by ergometric parameters.

Publication Types:

• Clinical Trial
• Randomized Controlled Trial

PMID: 2947149 [PubMed - indexed for MEDLINE]

8: Br J Clin Pharmacol 1994 Mar;37(3):279-88

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Trimetazidine: a new concept in the treatment of angina. Comparison with propranolol in patients with stable angina. Trimetazidine European Multicenter Study Group.

Detry JM, Sellier P, Pennaforte S, Cokkinos D, Dargie H, Mathes P.

Saint-Luc University Hospital, Brussels, Belgium.

1. Trimetazidine has a direct anti-ischaemic effect on the myocardium without altering the rate x pressure product or coronary blood flow. 2. The effects of trimetazidine (20 mg three times daily) were compared with those of propranolol (40 mg three times daily) in a double-blind parallel group multicentre study in 149 men with stable angina. 3. Reproducibility of exercise performance was verified during a 3 week run-in placebo washout period. All patients had > 1 mm ST-depression on exercise test. 4. After 3 months, similar anti-anginal efficacy was observed between the trimetazidine (n = 71) and propranolol (n = 78) groups. No significant differences were observed between trimetazidine and propranolol as regards anginal attack rate per week (mean difference P-TMZ: 2; 95% CI: -4.4, 0.5) and exercise duration (mean difference P-TMZ: 0 s; 95% CI: -33, 34) or time to 1 mm ST segment depression (mean difference P-TMZ: 13 s; 95% CI: -24, 51). Heart rate and rate x pressure product at rest and at peak exercise remained unchanged in the trimetazidine group but significantly decreased with propranolol (P < 0.001 in all cases). With both drugs there was a trend to decreased ischaemic episodes in the 46% patients who experienced ambulatory ischaemia on Holter monitoring. Six patients stopped trimetazidine and 12 propranolol. Of these, five in each group were withdrawn because of deterioration in cardiovascular status. 5. The results suggest that trimetazidine and propranolol at the doses studied have similar efficacy in patients with stable angina pectoris.(ABSTRACT TRUNCATED AT 250 WORDS)

Publication Types:

• Clinical Trial
• Multicenter Study
• Randomized Controlled Trial

PMID: 8198938 [PubMed - indexed for MEDLINE]

9: Cardiovasc Drugs Ther 1990 Aug;4 Suppl 4:853-9

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Comparison of trimetazidine with nifedipine in effort angina: a double-blind, crossover study.

Dalla-Volta S, Maraglino G, Della-Valentina P, Viena P, Desideri A.

Department of Clinical Medicine, University of Padova Medical School and Hospital, Italy.

Trimetazidine has been shown to have an antianginal effect, increasing exercise capability without producing any significant change of heart rate or systolic blood pressure. The aim of this study was to compare trimetazidine efficiency to that of another classical antianginal drug. A double-blind crossover trimetazidine versus nifedipine trial was carried out in 39 male patients, mean age 58 years, with effort angina for 5 years on average, and a mean number of weekly attacks of 2.4. Thirteen patients had previous myocardial infarction. Nineteen patients received nifedipine (40 mg per day) then trimetazidine (60 mg per day), and 20 patients received the drugs in the opposite order. Each therapeutic period of 6 weeks was preceded by 1 week of washout with placebo. Drug efficacy was assessed by a bicycle exercise tolerance test, performed at the beginning and at the end of each therapeutic period, and by clinical symptoms observed with placebo or with treatment. The statistical analysis was performed according to a crossover design, with repeated measurements. The decrease of the number of weekly attacks was not significantly different with trimetazidine and nifedipine. Results on the exercise test showed no significant differences for maximum workload, the duration of exercise, ST-segment depression at peak exercise, and the time to 1-mm ST-segment depression. Heart rate and systolic blood pressure were not significantly different at rest and at peak exercise. However, the change in the rate-pressure product at the same workload differed significantly between the drugs: It decreased with nifedipine and remained unchanged with trimetazidine, indicating the difference to be in the mode of action of the drug.(ABSTRACT TRUNCATED AT 250 WORDS)

Publication Types:

• Clinical Trial
• Randomized Controlled Trial

PMID: 2093381 [PubMed - indexed for MEDLINE]

10: Heart 1997 Oct;78(4):353-7

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Combination treatment with trimetazidine and diltiazem in stable angina pectoris.

Manchanda SC, Krishnaswami S.

Department of Cardiology, All India Institute of Medical Sciences, New Delhi, India.

OBJECTIVE: To assess antianginal efficacy and possible adverse haemodynamic effects of combination treatment with trimetazidine and diltiazem in patients with stable angina. DESIGN: Double blind, randomised, placebo controlled trial of four weeks duration. SETTING: Outpatient department of two Indian hospitals. SUBJECTS: 64 male patients with stable angina, uncontrolled on diltiazem alone. INTERVENTIONS: Diltiazem 180 mg and trimetazidine 60 mg, or diltiazem 180 mg and placebo daily. MAIN OUTCOME MEASURE: Change in exercise time to 1 mm ST segment depression. RESULTS: 33 patients (55%) had no exercise induced angina at 3 mm ST segment depression at inclusion in the study (silent ischaemia). Intention to treat analysis showed that of 32 patients in each treatment group, the number (%) of patients responding to trimetazidine compared to placebo was: for anginal attacks, 28 (87.5) v 15 (46.9), p < 0.001; for exercise time to 1 mm ST segment depression, 21 (65.6) v 9 (28.1), p < 0.003; for exercise time to angina, 12 (37.5) v 5 (15.6), p < 0.05; and for maximum work at peak exercise, 17 (53.1) v 8 (25), p < 0.02. Compared to placebo, there was net improvement with trimetazidine in mean anginal attacks of 4.8/ week (95% confidence interval (CI) 7.5 to 2.1; p < 0.002); in mean exercise times at 1 mm ST segment depression of 94.2 seconds (95% CI 182.8 to 5.6; p < 0.05), and at onset of angina of 113.1 seconds (95% CI 181.6 to 44.6; p < 0.02); and in mean maximum work at peak exercise of 1.4 metabolic equivalents (95% CI 2.4 to 0.3; p < 0.05). CONCLUSIONS: Patients with stable angina uncontrolled with diltiazem had a clinically important improvement after combination treatment with trimetazidine, without adverse haemodynamic events or increased side effects.

Publication Types:

• Clinical Trial
• Randomized Controlled Trial

PMID: 9404250 [PubMed - indexed for MEDLINE]

11: Am J Cardiol 1995 Aug 24;76(6):12B-16B

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Combination therapy of trimetazidine with diltiazem in patients with coronary artery disease. Group of South of France Investigators.

Levy S.

Division of Cardiology, Hopital Nord, University of Marseille School of Medicine, France.

The efficacy of trimetazidine, an antianginal agent with a direct effect on ischemic myocardium, has been tested alone or in combination with beta blockers or nifedipine. The combination with diltiazem, a widely used calcium antagonist, has not been studied. The aim of this study was to evaluate the potential benefit of oral trimetazidine (20 mg 3 times daily) in combination with oral diltiazem (60 mg three times daily). This was a multicenter, placebo-controlled study with a follow-up period of 6 months. Patients with stable angina and a positive exercise electrocardiogram before and after 15 days of diltiazem therapy were included. The 67 patients were randomized to diltiazem plus placebo (group I, 35 patients) and diltiazem plus trimetazidine (group II, 32 patients). Follow-up included a bicycle ergometer maximal exercise test and a physical examination at inclusion and at 3 and 6 months. The 2 groups were similar in terms of ergometric parameters, except for the ischemic threshold, defined as the time to 1-mm ST-segment depression. The latter was shorter in group II. Comparison of exercise tests performed at inclusion and after 6 months of therapy in both groups showed that the ischemic threshold was significantly prolonged (2 minutes 41 seconds; p < 0.001) in group II. This was not the case for group I, which showed a 41-second prolongation only (difference not significant). The work (kPM) produced at 1-mm ST-segment depression was also significantly increased in group II (1,445.9 kPM; p < 0.001) compared with group I (563.7 kPM; p = 0.012).(ABSTRACT TRUNCATED AT 250 WORDS)

Publication Types:

• Clinical Trial
• Multicenter Study
• Randomized Controlled Trial

PMID: 7645522 [PubMed - indexed for MEDLINE]

12. Michaelides AP, Spiropoulos K, Dimopoulos K Antianginal efficacy of the combination of trimetazidine-propranolol compared with isosorbide dinitrate-propranolol in patients with stable angina. Clin Drug Invest 1997; 13(1): 8–14.
13. Swed H, Sadowski Z, Pachocki R Efficacy and safety of trimetazidine in patients with persistent stable angina pectoris under b-blocker therapy TRIMPOL II multicentre study. Eur Heart J 1999; 20 (abstract suppl): 2516.

14: Am J Cardiol 1998 Oct 1;82(7):898-901

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Effects of trimetazidine on ischemic left ventricular dysfunction in patients with coronary artery disease.

Lu C, Dabrowski P, Fragasso G, Chierchia SL.

Istituto Scientifico H. San Raffaele, Milan, Italy.

We studied 15 patients with chronic coronary artery disease (13 men aged 62 +/- 8 years) undergoing dobutamine (5 to 40 microg/kg/min) echocardiography at the end of two 15-day treatment periods with placebo and trimetazidine (20 mg 3 times daily) given in random order, according to a double-blind, crossover design. Results show that trimetazidine improves resting left ventricular function and reduces the severity of dobutamine-induced ischemic myocardial dysfunction.

Publication Types:

• Clinical Trial
• Randomized Controlled Trial

PMID: 9781975 [PubMed - indexed for MEDLINE]

15. Swed H, Sadowski Z, Pachocki R  The antiischemic effects and tolerability of trimetazidine in coronary diabetic patients. Cardiovasc Drugs Ther 1999; 13: 217–222.
16. Swed H, Sadowski Z, Pachocki R  Anti-ischaemic efficacy and tolerability of trimetazidine in elderly patients with angina pectoris. Clin Drug Invest 2000; 19(1): 1–8.

17: Am J Cardiol 1994 Aug 1;74(3):226-31

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Characteristics of a contemporary population with angina pectoris. TIDES Investigators.

Pepine CJ, Abrams J, Marks RG, Morris JJ, Scheidt SS, Handberg E.

Department of Medicine, University of Florida, Gainesville.

To characterize a contemporary, nonhospitalized population with angina pectoris, data were obtained from a geographically diverse cohort of 5,125 outpatients with chronic stable angina cared for by 1,266 primary care physicians between September and November of 1990. Diagnosis was based on history supported by evidence for coronary artery disease (coronary angiography, old myocardial infarction, or an abnormal stress test, either alone or in combination). The mean age of the patients was 69 years and 53% were women. Seventy percent had > 1 associated illness and 64% took > 1 cardiovascular drug. Median angina frequency was approximately 2 episodes/week and increased angina frequency (p < 0.0001) was associated with decreased overall feeling of well-being. Although effort angina was present in 90% of patients, 47% also had rest angina and 35% had mental stress-evoked angina. Female gender (relative risk [RR] 1.09; 95% confidence interval [CI] 1.02 to 1.16), concomitant illness (RR 1.17; CI 1.09 to 1.25), and pharmacotherapy (RR 1.14; CI 1.07 to 1.22) were associated with excess risk for rest angina. Younger age (RR 1.30; CI 1.20 to 1.41), female gender (RR 1.16; CI 1.07 to 1.26), concomitant illness (RR 1.13; CI 1.03 to 1.24), and pharmacotherapy (RR 1.28; CI 1.15 to 1.93) were associated with excess risk for mental stress angina. These data suggest that contemporary outpatients with angina are frequently women and elderly patients with high rates of associated illness, rest, and mental stress-related angina.

Publication Types:

• Clinical Trial

PMID: 8037126 [PubMed - indexed for MEDLINE]