Effects Of Trimetazidine In Patients Research Articles

Cardio-protective effect of trimetazidine in patients with disseminated breast cancer

Abstract Funding Acknowledgements Type of funding sources: None. Relevance of the problem. Anthracycline cardiotoxicity is the most unfavorable form due to irreversible complications of cardiovascular system caused by anthracyclines during the chemotherapy (CT) of the breast cancer (BC). Despite the fact that this type of cardiotoxicity has been studied better than others, the problem of preventing such complications remains relevant to this day. In our study, we suggest Trimetadizine (TMZ) as a cardioprotective agent in patients with disseminated breast cancer receiving Doxorubicin chemotherapy. Material and methods The study included 93 patients (aged 41.2±8.3 years) who underwent surgery for breast cancer and several courses of chemotherapy with Doxorubicin (according to the stage of breast cancer). Patients were randomized into 2 groups: the first group (n=47; G1) received TMZ at a dose of 70 mg daily, in the control group (n=46; G2) patients didn't receive TMZ. All patients before the start of the study underwent a complete echocardiographic examination and checked cardiac biomarkers such as troponin and brain natriuretic peptide (BNP). The exclusion criterion was patients with any kind of cardiovascular pathology. The primary endpoint of the study was a reduction in left ventricular ejection fraction (LVEF) deterioration as assessed by series of echocardiographic studies conducted after each course of chemotherapy, and then every 3 months after completion of chemotherapy for 1 year. Secondary outcome measures included echocardiographic (EchoCG) measurements of LV diastolic dysfunction, structural myocardial changes assessed by echocardiography, and control cardiac biomarkers. Results Both groups achieved the same cumulative dose of Doxorubicin. No patient died or discontinued chemotherapy during the study. There were no significant differences between the two groups in terms of baseline clinical findings, echocardiographic parameters, and changes in biomarkers. 3-5 months after the start of CT, standard echocardiography showed unreliable changes in LVEF, shortening fraction, and LV measurements. However, tissue Doppler showed a decrease in myocardial velocity (P = 0.001) in G2, indicating LV diastolic dysfunction. While no such changes were observed in G1. Conclusion Tissue Doppler proved to be more sensitive than standard echocardiography for early diagnosis of cardiac dysfunction, and TMZ appears to have a cardioprotective effect in case of anthracycline cardiotoxicity.

Effects of trimetazidine in patients with severe chronic heart failure with reduced left ventricular ejection fraction: A prospective, randomized, open-label, cross-over study.

BackgroundTrimetazidine (TMZ) modulates cardiac metabolism, but its use in heart failure remains controversial. The aim of the study was to evaluate the effects of TMZ on exercise capacity, left ventricular ejection fraction (LVEF), mortality, and quality of life in stable patients with heart failure with reduced left ventricular ejection fraction (HFrEF).MethodsForty-five patients with stable advanced HFrEF treated with optimal medical therapy were randomized in a prospective, single-center, open-label, cross-over study of TMZ (35 mg b.i.d.) on top of standard medical therapy or standard pharmacotherapy for two periods of 30 days and one period of 6 months. Initially and at the end of each period all patients underwent the following: exercise testing, six-minute walk test (6MWT), two-dimensional-echocardiography, and quality of life assessment.ResultsThe mean age of patients was 58.2 ± 10.6 years. Etiology of HFrEF was ischemic in 66.6% of patients. After 6 months no significant changes were observed in either group with regards to peak VO2 uptake, 6MWT, LVEF, or quality of life. TMZ had no effect on mortality or cardiovascular events.ConclusionsThe additional use of TMZ on top of standard medical therapy in stable advanced HFrEF patients was not associated with significant changes in mortality, exercise capacity, LVEF, or quality of life.

Trimetazidin hatása a primer perkután koronáriaintervención átesett akut koronáriaszindrómás betegekben : Szisztematikus irodalmi áttekintés és metaanalízis

Effect of trimetazidine in patients with acute coronary syndrome, undergoing primary percutaneous coronary intervention. Systematic review and meta-analysis Aims: The aim of our study is to review and meta-analytically analyze data from studies published comparing patients with acute coronary syndrome who have undergone primary PCI and received trimetazidin additionally to the optimal medical therapy or placebo during the reperfusion procedure. Methods and results: Our meta-analysis follows the points of PRISMA protocol and meets all of their criteria. We managed a search in three scientific database using the following keyword combination (coronar* OR heart disease ORacs) AND (trimetazidine). 917 publications were collected and a statistical analysis was performed on nine ran­domized-controlled trials (RCT). Three outcomes was analyzed by mean difference calculation, changes in left ventricle ejection fraction (LVEF), cardiac troponin I (cTnI) and high-sensitivity C-reactive protein (hs-CRP) levels. For the LVEF a significant increase was observed in the trimetazidin group (MD: 3.4%, CI: 1.393–5.408, P=0.001). There was significant improvement in the level of cTnI compared pre- and post-procedurally. (MD: 0.426, CI: 0.060–0.791, P=0.022). Non-significant improvement was measured in the hs-CRP level (MD: 1,214, CI: –0.122–2.549, P=0.075). Conclusions: Based on the results of our meta-analysis it can be suggested that the trimetazidine administered as adjunctive therapy in the treatment of primary PCI in patients with ACS yielded significant results in two of the three parameters we studied, which were improvement in LVEF and change in cTnI, while the third parameter, in the case of hs-CRP not-significant change was measurable. In evaluating our results, we took into account whether the participants did or did not fully receive optimal medical therapy (OMT) and numerous limitating factors.

Cardioprotective effect of Trimetazidine in patients with early breast cancer receiving anthracycline-based chemotherapy

Abstract Background Anthracyclines, alone or in combination with other drugs, are among the most effective chemotherapeutic agents to treat breast cancer both in the adjuvant and neoadjuvant settings. Unfortunately, anthracycline-associated dose-dependent cardiotoxicity is a limiting factor in clinical use. Extensive efforts have been devoted to identifying strategies to prevent anthracycline-induced cardiotoxicity. However, most cardioprotective agents have shown little efficacy in clinical trials. We hypothesized that myocardial damage by anthracyclines could be rationally prevented by using trimetazidine (TMZ), previously reported to interfere with anthracycline- and trastuzumab-induced cardiotoxicity. Therefore, we planned a randomized, controlled, open trial to determine whether TMZ may prevent the development of left ventricular (LV) dysfunction in patients receiving standard treatment for breast cancer. Methods The trial included 73 patients (41.2±8.1 years) undergoing surgery for breast cancer, who were scheduled for adjuvant epirubicin-containing chemotherapy and, if indicated, trastuzumab. Patients were randomly allocated in a 1:1 ratio to receive TMZ or baseline therapy only (control group). The main study endpoint was a reduction in the deterioration of left ventricular ejection fraction (LVEF), as evaluated by serial echocardiography performed at randomization and then every 3 months after the start of chemotherapy and for 1 year after its completion. Secondary outcome measures included echocardiographic indices of LV diastolic dysfunction, structural myocardial alterations, as assessed by speckle tracking echocardiography, and changes in cardiac biomarkers (troponin and brain natriuretic peptide). Results We found no significant differences between the two groups regarding baseline clinical and echocardiographic parameters. The two groups reached a similar cumulative dose of doxorubicin. No patient died during the study and no patients withdrew from chemotherapy. Three months after the start of chemotherapy, nonsignificant changes were observed in LVEF, shortening fraction, and LV diameters. No significant changes in cardiac biomarkers were observed in either group. Tissue Doppler imaging detected a significant decrease in myocardial velocities (P=0.001) in the control group, indicating LV diastolic dysfunction. In the same group, speckle tracking imaging revealed a statistically significant alteration in ventricular deformation (P=0.01), which means a decrease in LV systolic function. In the TMZ group, no significant alterations in LV diastolic function were observed. Conclusions Tissue Doppler imaging and speckle tracking imaging are more sensitive than conventional echocardiograms in the early diagnosis of cardiac dysfunction and TMZ seems to have an important role in the prevention of cardiotoxicity. Funding Acknowledgement Type of funding source: None

P3448Nephroprotective effect of Trimetazidine in patients with ischemic heart failure and chronic kidney disease

P3448Nephroprotective effect of Trimetazidine in patients with ischemic heart failure and chronic kidney disease

Effect of Trimetazidine in Patients Undergoing Percutaneous Coronary Intervention: A Meta-Analysis.

Optimizing the metabolism of the myocardium is a new strategy for patients with ischemic heart disease. Many studies have reported beneficial effects of trimetazidine (TMZ) on the clinical prognosis of patients with ischemic heart disease, but whether these beneficial effects are extended to patients undergoing percutaneous coronary intervention (PCI) remains uncertain. A meta-analysis was performed to evaluate the effect of TMZ on patients undergoing PCI. We conducted an electronic search of PubMed, Cochrane databases, the China National Knowledge Infrastructure, and Chinese Biological Medicine Database to identify randomized controlled trials. Methodological quality was assessed according to the Jadad scale score, and the meta-analysis was performed using Cochrane Collaboration RevMan 5.2 and Comprehensive Meta-Analysis. Dichotomous data were analyzed using relative risk (RR) or odds ratio (OR) with effect size indicated by the 95% confidence interval (CI), and continuous variables were analyzed using weighted mean differences (WMD) with effect size indicated by the 95% CI. Sensitivity analysis was performed by changing the statistical methods and effect model. Nine studies involving a total of 778 patients were included in this meta-analysis. Additional use of TMZ significantly improved the left ventricular ejection fraction (WMD: 3.11, 95% CI: [2.26, 3.96]) and reduced elevated cardiac troponin Ic level (RR: 0.69, 95% CI: [0.48, 0.99]), angina attacks during PCI (OR: 0.16, 95% CI: [0.07, 0.38]), and ischemic ST-T changes on the echocardiogram during PCI (RR: 0.76, 95% CI: [0.59, 0.98]). However, no significant difference was observed in serum BNP level 30 days after PCI between the experimental and control group. Additional use of TMZ for patients undergoing PCI may reduce myocardial injury during the procedure and improve cardiac function.

Trimetazidine and Cardioprotection

Trimetazidine (TMZ) is a metabolic agent used in cardiology for more than 40 years. Several studies assessed the cardioprotective effects of TMZ in patients with chronic coronary heart disease (CHD) as well as in patients with heart failure (HF). In light of the inclusion of TMZ in the current guidelines on the management of stable CHD, we reviewed the published literature on TMZ, focusing mainly its effects on patients with stable angina and HF. According to the published literature, there is sufficient evidence to support the addition of this agent in the treatment of symptomatic patients with stable angina.

Effects of trimetazidine in patients with acute myocardial infarction: data from the Korean Acute Myocardial Infarction Registry

Excess myocardial fatty acid oxidation can cause a range of deleterious myocardial effects. Trimetazidine (TMZ) is a clinically effective antianginal agent that selectively inhibits long-chain 3-ketoacyl CoA thiolase, reducing fatty acid oxidation and stimulating glucose oxidation. The role of TMZ in acute myocardial infarction (AMI), however, remains unclear. Our retrospective analysis explores the effect on clinical outcomes of adding TMZ to standard treatment in patients with AMI. All 13,733 AMI patients registered in the Korean Acute Myocardial Infarction Registry from 2005 to 2008 were retrospectively enrolled. Patients were divided into two groups: those treated with TMZ during their in-hospital management period and those who were not. Primary endpoints were all-cause death combined in-hospital and 12-month death and major adverse cardiac events (MACE), which included all-cause death, recurrent myocardial infarction (MI), repeated percutaneous coronary intervention (PCI) for target lesion revascularization (TLR), and coronary artery bypass graft. Propensity-matched patients were analyzed using an adjusted Cox proportional hazards model. Baseline clinical and angiographic characteristics in the TMZ and no-TMZ groups were generally similar, with the exceptions of pre-PCI thrombolysis in myocardial infarction flow grade, stent type, and stent length. Over 12 months, the relative risk of all-cause death fell by 59 % (event rate 2.3 vs. 6.4 %; hazard ratio 0.41, 95 % CI 0.18-0.97, P = 0.042) and the relative risk of MACE fell by 76 % (event rate 2.3 vs. 9.5 %; hazard ratio 0.24, 95 % CI 0.10-0.56, P = 0.001) in the TMZ group compared with those in the no-TMZ group. Trimetazidine appeared to improve clinical outcomes in AMI patients by significantly reducing all-cause mortality and MACE over 12 months.

Trimetazidine added to combined hemodynamic antianginal therapy in patients with type 2 diabetes: a randomized crossover trial

In nondiabetic patients with stable angina, combined treatment with hemodynamic agents and trimetazidine is well-tolerated and effective in controlling ischemia. This study aims to evaluate the antiischemic and metabolic effects of trimetazidine in patients with type 2 diabetes mellitus, not eligible for revascularization, who remained symptomatic despite the use of at least 2 antianginal agents. A randomized, double-blind, crossover clinical trial was used. Ten patients were randomized to receive trimetazidine (20 mg, 3 times a day) or placebo for 6-week periods. At baseline and at the end of each 6-week intervention period, clinical and biochemical evaluations, exercise testing, 24-hour ambulatory blood pressure, and Holter monitoring were performed. During trimetazidine therapy, patients had significant improvement on angina functional class (P < .05), with decrease in the number of weekly angina episodes (1.5 +/- 0.8 vs 0.4 +/- 0.7, P < .01), and in sublingual nitrate doses (1.4 +/- 0.7 mg vs 0.1 +/- 0.3 mg, P < .001). Time to 1-mm ST-segment depression during exercise test was increased after trimetazidine use (229 +/- 126 seconds at baseline, 276 +/- 101 seconds after placebo, and 348 +/- 145 seconds after trimetazidine, P < .001). No differences were observed between treatment periods on mean 24-hour blood pressure, heart rate, and rate-pressure product evaluated concomitantly with ambulatory blood pressure and Holter monitoring. Glycemic and lipid profiles were similar after trimetazidine and placebo use. In patients with diabetes who remain symptomatic, the addition of trimetazidine improves symptoms and exercise responses without hemodynamic or metabolic changes. The present data suggest that trimetazidine may be an effective adjunct therapy for these patients, but further investigation is needed to confirm these findings.

Trimetazidine to reverse ischemia in patients with class I or II angina: a randomized, double-blind, placebo-controlled dobutamine–atropine stress echocardiography study

We sought to evaluate the effects of trimetazidine on ischemia induced by dobutamine-atropine stress echocardiography in patients with class I or class II angina. In a randomized, double-blind, placebo-controlled study, 66 patients with proved coronary disease were subjected to dobutamine-atropine stress echocardiography. Ischemia was proved in 56 patients who were included in the study and who had been on standard maintenance medications (propranolol, aspirin and statin). They were randomized to placebo or trimetazidine, 20 mg three times daily for a 12-week period, when dobutamine-atropine stress echocardiography was repeated. Fifty-two patients (56.53+/-8.9 years old) completed the study. No differences were seen between groups at entry. Thirty patients had class I and 26 class II angina. At the end of the study, 42 had class I and 14 class II angina (P=0.01), owing to patients being in the trimetazidine arm. We did not observe any differences between groups either for onset time of ventricular ischemic dysfunction, or for wall-motion score index. Comparing variation at peak using the delta wall-motion score index, we observed no differences, but only a trend toward reduction favoring trimetazidine (P=0.09). We did not detect a significant anti-ischemic effect of trimetazidine in patients with mild angina, but there was a clear improvement in angina class.

The anti-ischemic effect of trimetazidine in patients with postprandial myocardial ischemia is unrelated to meal composition

Background Previous studies provide evidence for a significant reduction of coronary flow reserve after ingestion of meals of different compositions. A possible role of hyperinsulinemia and increased free fatty acid levels, which are deleterious during acute myocardial ischemia and reperfusion, has been hypothesized. We assessed in patients with stable coronary disease the effects of high-fat meals (HFMs) and high-carbohydrate meals (HCMs) on ischemic threshold and stress left ventricular function on placebo and after partial fatty acid inhibition by trimetazidine (TMZ). Methods Ten patients (9 men, age 68 ± 7 years) were allocated to placebo and TMZ (40 mg TID), both administered in the 24 hours preceding testing, according to a randomized double-blind study design. All patients underwent stress (treadmill exercise testing according to the Bruce protocol) echocardiography after fasting (8 hours) and after an HFM and HCM (2 hours) either on placebo or on TMZ. Time to 1-mm ST-segment depression (time to 1 mm) and stress wall motion score index (WMSI) were evaluated. Results An HFM did not affect exercise variables compared with fasting, whereas an HCM resulted in a reduction of the ischemic threshold (time to 1 mm from 402 ± 141 to 292 ± 123 seconds, P = .025). Compared with placebo, TMZ improved time to 1 mm after fasting, HFM, and HCM (432 ± 153 vs 402 ± 141, 439 ± 118 vs 380 ± 107, 377 ± 123 vs 292 ± 123, F 1,9 = 26.91, P = .0006). Compared with placebo, on TMZ, stress WMSI decreased from 1.55 ± 0.25 to 1.29 ± 0.14 after fasting, from 1.57 ± 0.10 to 1.39 ± 0.28 after HFM, and from 1.64 ± 0.21 to 1.39 ± 0.21 after HCM (F 1,9 = 37.04, P = .0002). Interestingly, stress WMSI on TMZ was never different from rest WMSI on placebo. Conclusions In patients with coronary disease, exercise testing after an HCM results in more severe myocardial ischemia compared with that after an HFM. The observed beneficial effects of the partial fatty acid inhibitor TMZ seem to be unrelated to meal composition and are possibly caused by the better glucose use induced by the drug.

122 Long-term cardioprotective effects of trimetazidine in patients with ischemic dilated cardiomyopathy

122 Long-term cardioprotective effects of trimetazidine in patients with ischemic dilated cardiomyopathy

Short- and long-term beneficial effects of trimetazidine in patients with diabetes and ischemic cardiomyopathy

Background Trimetazidine (TMZ) has been shown to partially inhibit free fatty acid oxidation by shifting substrate utilization from fatty acid to glucose. The aim of this study was to assess the effects of TMZ in patients with diabetes and ischemic cardiomyopathy. Methods Sixteen patients with diabetes and ischemic hypokinetic cardiomyopathy (all males) on conventional therapy were randomized to receive either placebo or TMZ (20 mg 3 times per day), each arm lasting 15 days, and then again to receive either placebo or TMZ for 2 additional 6-month periods, according to a double-blind, crossover design. At the end of each period, all patients underwent exercise testing, 2-dimensional echocardiography, and hyperinsulinemic/euglycemic clamp. Among the others, New York Heart Association class, ejection fraction, exercise time, fasting blood glucose, end-clamp M value (index of total body glucose disposal) and endothelin-1 levels were evaluated. Results Both in the short and long term (completed by 13 patients), on TMZ compared to placebo, ejection fraction (47 ± 7 vs 41 ± 9 and 45 ± 8 vs 36 ± 8%, P < .001 for both) and M value (4.0 ± 1.8 vs 3.3 ± 1.6, P = .003, and 3.5 ± 1.5 vs 2.7 ± 1.6 mg/kg body weight/min, P < .01) increased, while fasting blood glucose (121 ± 30 vs 136 ± 40, P = .02 and 125 ± 36 vs 140 ± 43, P = .19) and endothelin-1 (8.8 ± 3.8 vs 10.9 ± 3.8, P < .001 and 6.2 ± 2.4 vs 9.2 ± 4.3 pg/mL, P = .03) decreased. In the short term, 10 patients decreased 1 class on the NYHA scale during treatment with TMZ ( P = .019 vs placebo). Eight patients decreased 1 NYHA class while on long-term TMZ treatment, while on placebo 1 patient increased 1 NYHA class and none improved ( P = .018 vs placebo). Conclusions In a short series of patients with diabetes and ischemic cardiomyopathy, TMZ improved left ventricular function, symptoms, glucose metabolism, and endothelial function. Shifting energy substrate preference away from fatty acid metabolism and toward glucose metabolism by TMZ appears an effective adjunctive treatment in patients with diabetes with postischemic cardiomyopathy.