[Efficacy and tolerance of trimetazidine, a metabolic antianginal, in combination with a hemodynamic antianginal in stable exertion angina. TRIMPOL I, a multicenter study]. / Efficacité et tolérance de la trimétazidine, antiangoreux métabolique, en association avec un antiangoreux hémodynamique dans l'angor d'effort stable. TRIMPOL I une étude multicentrique.

OBJECTIVE: Assess the antianginal and anti-ischemic effect of trimetazidine in patients with stable exercise-induced angina insufficiently controlled with conventional antianginal drugs. PATIENTS AND METHODS: The study population included patients with coronarographically documented stable exercise-induced angina and no other serious concomitant condition. For inclusion, patients had to have two comparably positive treadmill exercise tests. Conventional antiangina drugs (long-acting nitrate derivatives, beta-blockers or calcium antagonists) were continued as was any other therapy having no effect on the ECG ST segment. The patients were given a 4-week regimen of trimetazidine (20 mg t.i.d.) after the second positive treadmill test and final inclusion. At the end of this period, a final exercise test was performed. The study population included 700 patients (mean age 54 +/- 8.4 years, range 32-71 years, 615 men, 85 women) who completed the entire treatment protocol. RESULTS: The main findings observed after 4 weeks of treatment with trimetazidine were: significant lengthening of the total duration of exercise (486.6 s versus 443.7 s, p < 0.01)), increase in total work (10.6 METS versus 9.4 METS, p < 0.01), significant lengthening of delay to 1 mm ST depression (389.9 s versus 337.8 s, p < 0.01) and of the delay to onset of angina (450.3 s versus 251.7 s, p < 0.01). The other results were a significant reduction in the number of daily episodes of angina (2.47 versus 3.66, p < 0.01) and a reduction in mean use of complementary trinitrine (1.8 versus 2.94, p < 0.01). CONCLUSIONS: Four weeks of treatment with trimetazidine in combination with conventional antiangina drugs leads to a longer delay to development of 1 mm ST depression (ischemia threshold), significant lengthening of total duration of treadmill exercise, increased total work, and longer delay to angina theshold. Clinically, there was a reduction in the mean number of episodes of angina and a reduction in the use of trinitrine.

The antiischemic effects and tolerability of trimetazidine in coronary diabetic patients. A substudy from TRIMPOL-1.

Diabetes mellitus, a disease with a wide prevalence, has major cardiovascular effects, being a risk factor for the development of ischemic heart disease and congestive heart failure. The aim of this open, multicenter study was to assess the antiischemic efficacy and tolerability of trimetazidine, a metabolic agent acting at the myocardial mitochondrial level, in diabetic patients with stable effort angina treated previously with a single conventional antianginal drug. Fifty diabetic patients (mean age 58 years) with proven coronary artery disease, stable effort angina for at least 3 months, and positive, comparable results of two initial treadmill exercise tests separated by a 1-week interval were included in the study. They continued their conventional antianginal monotherapy with a long-acting nitrate, beta-blocker, or calcium channel blocker. After stabilization, 4-week therapy with trimetazidine, three times daily, 20 mg was initiated in combination with previous treatment. The results showed a significant improvement in exercise tolerance (440.2 vs. 383.2 s; P < 0.01), time to 1-mm ST-segment depression (358.3 vs. 301.6 s; P < 0.01), time to onset of anginal pain (400.0 vs. 238.3 s; P < 0.01), and total work (9.39 vs. 8.67 metabolic equivalents, P < 0.01). Maximal ST-segment depression was attenuated compared with baseline (1.82 vs. 1.91 mm). Other findings included a significant decrease in the mean frequency of anginal episodes (3.06 vs. 4.79 per week; P < 0.01) and in mean nitrate consumption (2.29 vs. 4.2 doses/week). These results suggest that trimetazidine may be effective and is well tolerated as combination therapy for diabetic coronary artery disease patients uncontrolled with a single hemodynamic agent.