Antiischemic efficacy of trimetazidine in patients with ischemic heart disease,stable angina pectoris and disturbances of carbohydrate metabolism

AIM: To compare antiischemic effects of trimetazidine in patients with stable angina pectoris with and without disturbances of carbohydrate metabolism. MATERIAL: Patients with ischemic heart disease, stable class II-III angina pectoris and reproducible positive results of on-treatment exercise tests (n=40, mean age 56.7-/+1.95 years, 37 men) with normal carbohydrate metabolism (group 1, n=20) and with disturbances of carbohydrate metabolism (group 2, n=20). METHODS: All patients in addition to individually selected antianginal therapy were given trimetazidine (60 mg/day) for 2 months. Bicycle exercise tests were repeated after 1 and 2 months. Patient's diaries were used for registration of anginal attacks and nitroglycerine consumption. RESULTS: Addition of trimetazidine was associated with significant (p<0.005) prolongation of exercise duration until 1 mm-ST depression in both groups. Exercise duration was 553-/+10.5 and 555-/+10.2 s (p>0.05) at baseline, 657-/+15.3 and 695-/+10.1 s (p<0.05) after 2 months in groups 1 and 2, respectively. Other effects of trimetazidine in groups 1 and 2 included increases of total work performed during exercise test (by 14 and 22%, respectively), decreases in numbers of patients with ST depression (by 40, p<0.05, and 50%, p<0.05, respectively), numbers of anginal attacks (by 30, p<0.001, and 43%, p<0.001, respectively) and nitroglycerine pills (by 13%, p<0.001 and 51%, p<0.001, respectively). The decrease in supplemental nitroglycerine consumption was significantly more pronounced in group 2 (p<0.0001). There was no significant increment in double product in both groups. CONCLUSION: Antiischemic effect of trimetazidine was greater in patients with angina pectoris and disturbances of carbohydrate metabolism than in similar patients without such disturbances. KEY WORDS. trimetazidine; diabetes, type II, ischemic heart disease; angina pectoris.     

Anti-ischemic efficacy of combination of trimetazidine with enalapril in patients with stable effort angina and metabolic syndrome

Efficacy of combination of trimetazidine (60 mg/day) and enalapril in patients with stable effort angina and metabolic syndrome was assessed in a randomized placebo controlled study of 64 patients. Anti-ischemic activity of trimetazidine was found to be significant. It was most pronounced in patients with abnormal 24-hour blood pressure index, waist/hip circumference ratio >1.0 at the background of satisfactory clinical and laboratory compensation of type 2 diabetes.     

曲美他嗪治疗冠心病伴糖尿病的疗效观察

目的 :观察曲美他嗪治疗伴有糖尿病的冠心病 (CHD)治疗效果。方法 :用曲美他嗪治疗 CHD伴有糖尿病 (A组 )与不伴有糖尿病 (B组 )两组各 4周 ,对两组治疗前后平板运动耐量指标变化进行对照。结果 :两组在治疗后的运动总步行时间、运动至心绞痛出现时间和运动到 ST段压低达到 0 .1m V所需时间均较治疗前有明显延长 (P <0 .0 5 ) ,但 A组的效果比 B组更显著 (P <0 .0 5 )。结论 :曲美他嗪治疗伴有糖尿病的 CHD效果比不伴有糖尿病的 CHD更显著。     

Assessment of efficacy and safety of nebivolol in patients with stable effort angina

AIM: To study efficacy and safety of nebivolol in patients with stable angina pectoris. MATERIAL: Twenty patients with stable effort angina pectoris and positive exercise test without contraindications to beta-blockers, signs of NYHA class III-IV heart failure, and obstructive lung disease. After 5-7 days of control period all patients were given nebivolol (starting dose 5 mg/day) for 8 weeks. Graded exercise tests on treadmill and patient's diaries were used for assessment of treatment efficacy. RESULTS: Treatment with nebivolol (5-10 mg o.d. ) was associated with significant slowing of heart rate, lowering of blood pressure, and increase of exercise duration until appearance of angina or 1 mm ST-segment depression. Nebivolol did not affect left ventricular ejection fraction, bronchial conductance, or results of biochemical tests (including lipid profile). Adverse reaction (dizziness which disappeared after lowering of a dose) was registered in 1 patient. CONCLUSION: Nebivolol is an effective drug for the treatment of patients with stable angina.     

Chronic effects of trimetazidine on ergometric parameters in effort angina

With the participation of B. Bouniol, Bourges; M. Gallet, Lyon; R. Gilly, C. Morbidelli, Menton; J.D. Le Roy, Tours; and J.P. Monassier, Colmar.     

Effects of myocardial revascularisation in patients with effort angina and those with effort and nocturnal angina

The effects of coronary artery bypass graft operation were studied in 32 patients with daytime ambulatory ST segment changes and 14 patients with daytime and nocturnal angina and ST segment changes. Patients had ambulatory ST segment monitoring and exercise testing before and after operation and coronary arteriography was repeated in 34 patients after operation. Before operation, patients with daytime and nocturnal ischaemia tended to have more severe coronary artery disease, lower exercise tolerance, and more frequent ambulatory ST segment changes than those who had daytime ST segment changes only. After operation chest pain recurred in 22% of patients and ST segment depression during exercise testing or ambulatory ST segment monitoring recurred in 37% of the patients and was significantly more frequent in those with nocturnal ischaemia than in those with daytime ischaemia. Graft patency rates were similar in patients with and those without recurrence of ischaemia. After operation the frequency and magnitude of ST segment changes and exercise duration were improved in patients with preoperative daytime angina and also in those with daytime and nocturnal angina. The improvement was more pronounced in the latter groups. Thus, absence of postoperative angina is not a reliable indicator of the absence of reversible myocardial ischaemia. After revascularisation, patients with rest and nocturnal angina can expect relief from ischaemia, and if this recurs postoperatively, the threshold is improved and pain usually occurs only on exertion.     

Effects of myocardial revascularisation in patients with effort angina and those with effort and nocturnal angina.

The effects of coronary artery bypass graft operation were studied in 32 patients with daytime ambulatory ST segment changes and 14 patients with daytime and nocturnal angina and ST segment changes. Patients had ambulatory ST segment monitoring and exercise testing before and after operation and coronary arteriography was repeated in 34 patients after operation. Before operation, patients with daytime and nocturnal ischaemia tended to have more severe coronary artery disease, lower exercise tolerance, and more frequent ambulatory ST segment changes than those who had daytime ST segment changes only. After operation chest pain recurred in 22% of patients and ST segment depression during exercise testing or ambulatory ST segment monitoring recurred in 37% of the patients and was significantly more frequent in those with nocturnal ischaemia than in those with daytime ischaemia. Graft patency rates were similar in patients with and those without recurrence of ischaemia. After operation the frequency and magnitude of ST segment changes and exercise duration were improved in patients with preoperative daytime angina and also in those with daytime and nocturnal angina. The improvement was more pronounced in the latter groups. Thus, absence of postoperative angina is not a reliable indicator of the absence of reversible myocardial ischaemia. After revascularisation, patients with rest and nocturnal angina can expect relief from ischaemia, and if this recurs postoperatively, the threshold is improved and pain usually occurs only on exertion.     

Leg showering therapy in patients with intermittent claudication

Ten patients with intermittent claudication were treated using a recently constructed "chair" in which the seated patient has alternately warm and cool water flushed over the legs and feet. A trial treatment was given for 25 minutes, three times a week for 5 weeks. Ankle/arm index, skin perfusion pressure and calf blood flow all remained unchanged immediately after such a series of treatment. Even at follow-up 6 months later, values were unchanged but for a minute increase in ankle/arm index in the poorer leg. Walking capacity was additionally measured and an improvement was seen, also after 6 months. The role of the contrast temperature treatment in this improvement is, however, unclear.     

曲美他嗪治疗不稳定型心绞痛的疗效分析

目的　观察曲美他嗪与传统药物相结合治疗对冠心病不稳定型心绞痛患者心肌缺血的保护作用。方法　将 60例冠心病不稳定型心绞痛患者随机分成两组 ,治疗组 3 0例 ,除用硝酸酯类、β-阻滞剂等传统药物治疗外 ,加用曲美他嗪 2 0 mg,每日 3次口服。对照组 3 0例接受传统药物治疗 ,连续观察 4周。观察两组患者心绞痛发作次数、心电图缺血性 ST-T的疗效及血压、心率的变化。结果　治疗组心绞痛发作次数较对照组明显减少分别为 [( 3 .2± 1.4)次 ,( 5 .7± 1.6)次 ]两组比较 P<0 .0 5 ,心电图缺血性 ST-T改善的疗效明显好于对照组 ,P<0 .0 5 ,而两组的心率、血压变化无明显差异。结论　曲美他嗪作为一种影响代谢的药物 ,对改善心肌缺血有良好的效果 ,且方法简便 ,疗效显著 ,安全可靠 ,易于接受。     

Clinical benefits of trimetazidine in patients with recurrent angina

In clinical practice there is a major problem with angina, which is resistant to medical therapy with hemodynamically acting agents. In that group of patients it is necessary to consider the indications for coronary angiography and percutaneous transluminal coronary angioplasty (PTCA) or coronary artery bypass grafts (CABG). But some of these patients, especially those who had previous CABG or PTCA, coronary diabetic patients and elderly patients do not qualify for revascularization procedures. In patients with recurrent angina the beneficial effect of trimetazidine, a metabolic agent, that shifts cardiac energy metabolism from fatty acid oxidation to glucose oxidation was demonstrated. In the TRIMPOL II analysis of subgroup of post-revascularized patients with recurrent angina was demonstrated the improvement in exercise treadmill test parameters and clinical symptoms in a group treated with trimetazidine added to preexisting monotherapy with metoprolol in comparison with placebo plus metoprolol. The time to 1 mm ST-segment depression was increased with trimetazidine by 80s and was significantly greater than that recorded in the placebo group (465+/-143.8s vs 385.1+/-144.6s, P<0.01). The time to onset of angina was significantly greater for the group treated with trimetazidine in comparison with placebo (508.1+/-132.4 vs 433.6+/-164s, P=0.031). The total duration of exercise was significantly greater than that recorded for patients with placebo plus metoprolol (524.4+/-131.5 vs 466.9+/-144.8, P=0.048). A similarly significant observation was made regarding workload (10.1+/-2.4 vs 9+/-2.4 METs, P=0.035). The maximum ST-segment depression at peak exercise was significantly smaller in the trimetazidine group than in placebo group (1.4+/-0.8 vs 1.8+/-0.7 mm, P<0.01). The mean number of angina attacks per week was 1.7+/-2.3 for patients in the trimetazidine treated group, as compared with 3.1+/-2.9 for patients receiving placebo (P<0.01). The rate-pressure product at peak of exercise remained unchanged. The results suggest the rationale for metabolic therapy in post-revascularized patients with recurrent angina. Because no influence on heart rhythm, blood pressure, blood glucose level and excellent tolerability, trimetazidine may be also especially recommended for elderly and coronary diabetic patients, especially those with impaired left ventricular function.     

曲美他嗪对稳定性劳力型心绞痛的疗效观察

目的 试验目的为评价曲美他嗪（ＴＭＺ）与传统药物相结合对稳定性劳力型心绞痛患抗心绞痛的疗效及耐受性。方法 在１周的时间内经２次运动试验。结果为阳性且运动持续时间变异低于１０％的１３８例稳定性劳力型心绞痛患入选试验。给予ＴＭＺ２０ｍｇ,每天３次联合单一的β阻滞剂、钙通道阻滞剂或长效的硝酸脂类治疗１２周。１３１例患完成试验。行统计学分析。结果 与试验前相比、运动耐量和总工作量显提高（Ｐ〈０．０     

The effectiveness of isoxsuprine in patients with intermittent claudication

Sixty male patients with intermittent claudication were investigated in a randomized, double-blind, placebo-controlled study in order to determine the effectiveness of Isoxsuprine. The analysis of the results was made on the basis of subjective assessment of symptoms by the patients themselves and also on the results of segmental blood-pressure measurements and ankle/arm indices at rest and after standardised exercise. Significant differences were demonstrated between the active and placebo groups as regards pain-free walking distance although arterial pressure measurements did not show statistically significant differences between the two groups. Isoxsuprine appears to be significantly beneficial only for patients with obstructions at the femoro-popliteal level.     

Diagnostic work-up of patients with intermittent claudication.

In this paper a number of techniques are described that provide information concerning the functional disturbances caused by anatomic lesions within the vascular system in patients with intermittent claudication. These techniques are part of a currently growing entity that is called the "Vascular Laboratory". Main characteristics of these techniques are that they are painless, atraumatic and without any danger to the patient. Therefore, they can both be used for diagnosis as well as for follow-up of the patients. Moreover, many of them are useful for detecting stenotic lesions at an early stage of evolution. In any patient with intermittent claudication, the walking distance, oscillography at rest and after exercise and systolic blood pressure determination should be performed. Segmental plethysmography is extremely sensitive mainly when performed together with systolic blood pressure determination. Venous occlusion plethysmography has been significantly improved in recent years and is capable of providing direct information concerning the circulation through the diseased limb. There seems to be tremendous improvement in the techniques using ultrasound allowing presently construction of an anatomic picture of the vessels (Ultrasonic arteriography).     

Prevalence of angina, myocardial infarction and intermittent claudication assessed by Rose Questionnaire among patients with Behcet's syndrome

Objective. To determine the risk of clinical cardiovasculardisease in middle-aged patients with Behcet's syndrome (BS)compared with gender-matched non-BS subjects. Methods. The prevalence of angina, myocardial infarction (MI),doctor diagnosed ischaemic heart disease (IHD) and intermittentclaudication were sought by the Rose Angina Questionnaire in225 (141 M/84 F) BS patients (mean age: 52 ± 8) withBS and 117 (74 M/43 F) controls (mean age: 50 ± 5). Informationon atherosclerotic risk factors was also collected. Results. The prevalence of angina, MI and doctor-diagnosed IHDwere not different between BS patients and non-BS controls inthe whole study population and when males and females were separatelyanalysed. Angina tended to be more common among females comparedwith males among both patients and controls. Intermittent claudicationwas found to be significantly more common among BS patients,especially in males with venous disease. Conclusions. The findings in this cross-sectional clinical studyare in line with previous observations not indicating acceleratedatherosclerosis in BS. Intermittent claudication might not bea suitable tool for the detection of peripheral atheroscleroticdisease especially among BS patients having venous disease. KEY WORDS: Behcet's syndrome, Atherosclerosis, Cardiovascular disease, Angina, Myocardial infarction, Peripheral arterial disease, Claudication Submitted 30 September 2007; revised version accepted 20 December 2007.     

Clinical efficacy of picotamide in long-term treatment of intermittent claudication

The clinical efficacy of picotamide was investigated in a randomized, double-blind, placebo-controlled study in patients with peripheral occlusive arterial disease of the lower limbs at functional stage II of the Fontaine classification. Forty patients with a history of claudication for at least six months were admitted to the study and were given either 3 x 300 mg tablets of picotamide (20 subjects) or three identical placebo tablets (20 subjects) for six months. The two groups of patients were similar in regard to clinical features and potential risk factors. At the end of treatment painfree walking distance and systolic ankle-arm pressure ratio improved more in the picotamide than in the placebo group (p = 0.05). Systolic ankle pressure curves, determined before and after the six-month treatment, showed a positive trend to a higher postexercise ankle pressure and a faster return to the preexercise levels in the picotamide group; however, the difference was not statistically significant. Laboratory monitoring revealed a slight prolongation of bleeding time, a significant decrease in arachidonic acid-induced platelet aggregation, and an enhanced fibrinolysis with absence of interference with hemostasis in the picotamide group. One patient in the placebo group developed a major cardiovascular event (angina pectoris) during the study. These results indicate that picotamide is an effective drug that may modify the natural course of intermittent claudication and associated vascular problems.