OBJECTIVE: To determine the effect of trimetazidine on cardiac function and exercise tolerance in primary hypertension patients with type 2 diabetic. METHODS: In this randomized, double-blind, placebo-controlled prospective study, 60 primary hypertensive patients with diabetic were equally assigned into two groups, patients received trimetazidine (20 mg, 3 times a day) or placebo for 1 year. Echocardiography, cardiopulmonary exercise testing were performed; and the plasma N terminal pro B type natriuretic peptide (NT-ProBNP), hr-CRP, TNF-α, angiotensin Ⅱ and endothelin concentration were determined before and after treatment. RESULTS: In trimetazidine group, the left ventricular mass index, the mitral flow velocity E wave to A wave ratio (E/A), the peak early diastolic velocity (V) to late diastolic velocity (V) ratio (V/V) and the peak systolic velocity (Vs) were significantly improved, the plasma NT-ProBNP level was significantly decreased, and the exercise time, metabolic equivalent, maximal oxygen uptake and anaerobic threshold were significantly increased (all <0.05); plasma concentration of hr-CRP, TNF-α, angiotensin Ⅱ and endothelin were significantly reduced after trimetazidine treatment, compared with baseline (all <0.05) and with placebo (all <0.05). There were no significant differences in any of above parameters after treatment in placebo group (all >0.05). No severe adverse reaction was observed in both groups. CONCLUSIONS For patients with both hypertension and diabetes, trimetazidine can improve cardiac function and increase exercise tolerance.
Diabetes Complications ; complications ; Diabetes Mellitus ; drug therapy ; Double-Blind Method ; Exercise Tolerance ; drug effects ; Heart ; drug effects ; Humans ; Hypertension ; complications ; drug therapy ; Natriuretic Peptide, Brain ; blood ; Prospective Studies ; Treatment Outcome ; Trimetazidine ; pharmacology ; therapeutic use ; Vasodilator Agents ; pharmacology ; therapeutic use

INTRODUCTION: Contrast-induced nephropathy (CIN) is a serious but preventable complication of coronary procedures. Trimetazidine (TMZ) has recently been explored for use in preventing post-procedural CIN due to its cellular anti-ischemic and antioxidant properties. The objective is to assess the efficacy of oral TMZ in the prevention of contrast induced nephropathy during elective coronary angiography and PCI among patients with renal impairment.

METHODS: We conducted a systematic search of the Cochrane Central Register of Controlled Trials, Pubmed/ MEDLINE, EMBASE, clinicaltrials.gov for articles published until June 2016 for randomized controlled trials examining the effects of adding oral TMZ to standard therapy in preventing CIN. Outcome measures were incidence of CIN, defined as a 0.5 mg/dl or ?25% increase in serum creatinine 48-72 hours after contrast exposure, and incidence of dialysisrequiring CIN. Validity of studies was assessed through a risk assessment tool available from Cochrane. Treatment effect was estimated by calculating the Mantel-Haenszelweighted risk ratio (RR) using a fixed-effects model available from RevMan 5.3.

RESULTS: A total of four studies comprising 714 patients (TMZ group=352, Control group=362) were included in the final analysis. Pooled results revealed the TMZ group was associated with significantly fewer incidences of CIN compared to control (RR 0.33, 95% confidence interval [CI], 0.20, 0.53; P<.00001), with a relative risk reduction of 67% and an absolute risk reduction of 11.04% (NNT=nine). No dialysis-requiring CIN was observed in the included studies.

CONCLUSION: The addition of oral TMZ to standard hydration confers a significant benefit in preventing CIN after coronary procedures among patients with mild to moderate renal impairment. We recommend the addition of TMZ to standard prevention strategies. However, a large well-designed trial should be conducted to determine its effect on other outcomes such as prevention of dialysis-requiring CIN and mortality. 

BACKGROUND: Ischemic heart disease is the most common type of heart disease and an important cause of death in Korea. Among marketed anti-anginal medications, molsidomine, nicorandil, and trimetazidine are approved in Korea with unique mechanism of actions. As these drugs are not approved by the US Food and Drug Administration, the access to the up-to-dated and comprehensive safety-related information has been less than optimal from drug information resources used by Korean pharmacists. METHODS: A systematic review was conducted using Embase and Korean manuscripts to compile safety updates for these medications. Out of 418 articles from keyword searches, 52 studies were reviewed in full to compare adverse effects (AEs) with the approved package inserts (PI). RESULTS: Molsidomine related adverse effects were mostly mild or moderate, but anxiety, palpitation, epigastric pain, and sexual potency reduction were additional AEs found from the review not listed in PI. Although PI has included ulceration in oral cavity and gastrointestinal tracts including anus by nicorandil, the Korea FDA recently recommended adding corneal, genital, and skin ulcers to the approved PI. Trimetazidine induced Parkinsonism, worsening of the symptoms for patients diagnosed with Parkinson's disease, gastrointestinal burning, and muscle cramps were additionally identified AEs not listed in PI for trimetazidine. CONCLUSION: Continuous evaluations of the safety profile of these agents are needed to balance the risks and benefits to provide evidence-based safety counseling to the patients. In addition, more focused efforts on spontaneous reporting are warranted by healthcare professionals to safeguard patients against AEs.
Anal Canal ; Anxiety ; Burns ; Cause of Death ; Counseling ; Delivery of Health Care ; Gastrointestinal Tract ; Heart Diseases ; Humans ; Korea ; Molsidomine* ; Mouth ; Muscle Cramp ; Myocardial Ischemia ; Nicorandil* ; Parkinson Disease ; Parkinsonian Disorders ; Pharmacists ; Product Labeling ; Risk Assessment ; Skin Ulcer ; Trimetazidine* ; Ulcer ; United States Food and Drug Administration

OBJECTIVES: To evaluate the efficacy of trimetazidine dihydrochloride as a treatment for chronic tinnitus. METHODS: A total of 97 chronic tinnitus patients were evaluated in this randomized, prospective, double-blind, placebo-controlled trial. After assessing for eligibility, 82 patients were randomly assigned into placebo or trimetazidine groups according to the medication. The trimetazidine group received 20×3 mg/day per oral trimetazidine dihydrochloride and the placebo group received 20×3 mg/day per oral placebo for 3 months. Tinnitus handicap inventory (THI), visual analogue scale (VAS) questionnaires and audiometric results were used to determine the effectiveness of trimetazidine treatment. RESULTS: The study group comprised 82 tinnitus subjects, 42 (51%) of whom received trimetazidine dihydrochloride and 40 (49%) who received placebo. There was no significant difference between placebo and trimetazidine groups in THI grade and VAS (both pre- and posttreatment scores) (P>0.05) and no significant improvement was observed in subjective loudness score in either group (P>0.05). Additionally there was no significant difference between groups in pre- and posttreatment pure tone hearing thresholds at all measured frequencies (P>0.05). CONCLUSION: Trimetazidine dihydrochloride therapy was ineffective for relieving chronic tinnitus.
Double-Blind Method* ; Hearing ; Humans ; Prospective Studies ; Tinnitus* ; Trimetazidine*

BACKGROUND AND OBJECTIVES: Studies reveal that the microvolt T wave alternans (MTWA) test has a high negative predictive value for arrhythmic mortality among patients with ischemic or non-ischemic cardiomyopathy. In this study, we investigate the effects of trimetazidine treatment on MTWA and several echocardiographic parameters in patients with stable coronary artery disease. SUBJECTS AND METHODS: One hundred patients (23 females, mean age 55.6±9.2 years) with stable ischemic heart disease were included in the study group. Twenty-five age- and sex-matched patients with stable coronary artery disease formed the control group. All patients were stable with medical treatment, and had no active complaints. Trimetazidine, 60 mg/day, was added to their current treatment for a minimum three months in the study group and the control group received no additional treatment. Pre- and post-treatment MTWA values were measured by 24 hour Holter testing. Left ventricular systolic and diastolic functions were assessed by echocardiography. RESULTS: After trimetazidine treatment, several echocardiographic parameters related with diastolic dysfunction significantly improved. MTWA has been found to be significantly improved after trimethazidine treatment (63±8 µV vs. 53±7 µV, p<0.001). Abnormal MTWA was present in 29 and 11 patients pre- and post-treatment, respectively (p< 0.001). CONCLUSION: Trimetazidine improves MTWA, a non-invasive determinant of electrical instability. Moreover, several echocardiographic parameters related with left ventricular functions also improved. Thus, we can conclude that trimetazidine may be an effective agent to prevent arrhythmic complications and improve myocardial functions in patients with stable coronary artery disease.
Cardiomyopathies ; Coronary Artery Disease* ; Coronary Vessels* ; Echocardiography ; Electrocardiography ; Female ; Humans ; Mortality ; Myocardial Ischemia ; Trimetazidine* ; Ventricular Function, Left

BACKGROUND AND OBJECTIVES: The aim of this study was to investigate the impact of treatment with oral trimetazidine (TMZ) applied before and after percutaneous coronary interventions (PCI) on short-term left ventricular functions and plasma brain natriuretic peptide (BNP) levels in patients with non-ST segment elevation myocardial infarction (NSTEMI) undergoing PCI. SUBJECTS AND METHODS: The study included 45 patients who were undergoing PCI with the diagnosis of NSTEMI. The patients were randomized into two groups. The first group (n=22) of the patients hospitalized with the diagnosis of NSTEMI was given conventional therapy plus 60 mg TMZ just prior to PCI. Treatment with TMZ was continued for one month after the procedure. TMZ treatment was not given to the second group (n=23). Echocardiography images were recorded and plasma BNP levels were measured just prior to the PCI and on the 1st and 30th days after PCI. RESULTS: The myocardial performance index (MPI) was greater in the second group (p=0.02). In the comparison of BNP levels, they significantly decreased in both of the groups during the 30-day follow-up period (29.0+/-8 and 50.6+/-33, p<0.01 respectively). However, decreasing of BNP levels was higher in the group administered with TMZ. The decrease of left ventriclular end-diastolic volume was observed in all groups at 30 days after intervention, but was higher in the group administered with TMZ (p=0.01). CONCLUSION: Trimetazidine treatment commencing prior to PCI and continued after PCI in patients with NSTEMI provides improvements in MPI, left ventricular end diastolic volume and a decrease in BNP levels.
Brain ; Echocardiography ; Follow-Up Studies ; Humans ; Myocardial Infarction ; Natriuretic Peptide, Brain ; Percutaneous Coronary Intervention ; Plasma ; Stroke Volume ; Trimetazidine ; Ventricular Function, Left

OBJECTIVES: Trimetazidine (TMZ) is known to reduce the generation of oxygen-derived free radicals. The objective of the present study was to evaluate the effects of TMZ on neomycin-induced ototoxicity in transgenic zebrafish (Brn3C: EGFP). METHODS: Five-day, postfertilization zebrafish larvae were exposed to 125 microM neomycin and one of the following TMZ concentrations for 1 hour: 10 microM, 100 microM, 500 microM, 1,000 microM, 1,500 microM, or 2,000 microM. Hair cells within the neuromasts of the supraorbital (SO1 and SO2), otic (O1), and occipital (OC1) lateral lines were analyzed using fluorescence microscopy and confocal microscopy (n=10). Hair cell survival was calculated as a percentage of hair cells in the control group that were not exposed to neomycin. Ultrastructural changes were evaluated using scanning electron microscopy. RESULTS: TMZ protected against neomycin-induced hair cell loss in the neuromasts (TMZ 1,000 microM, 11.2+/-0.4 cells; 125 microM neomycin only, 4.2+/-0.5 cells; n=10; P<0.05) and decreased the terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-biotin nick end labeling (TUNEL) reaction. In the ultrastructural analysis, structures of mitochondria and hair cells within the neuromasts were preserved in zebrafish exposed to 125 microM neomycin and 1,000 microM TMZ. CONCLUSION: TMZ attenuated neomycin-induced hair cell loss in zebrafish. The results of this study suggest that neomycin induces apoptosis, and that apoptotic cell death can be prevented by treatment with tremetazidine.
Apoptosis ; Cell Death ; Cell Survival ; DNA Nucleotidylexotransferase ; Free Radicals ; Hair* ; Larva ; Microscopy, Confocal ; Microscopy, Fluorescence ; Mitochondria ; Neomycin ; Trimetazidine* ; Zebrafish*

Animals ; Atrial Fibrillation ; drug therapy ; Dogs ; Female ; Heart Atria ; drug effects ; ultrastructure ; Male ; Malondialdehyde ; metabolism ; Microscopy, Electron, Transmission ; Platelet Activation ; drug effects ; Trimetazidine ; pharmacology ; therapeutic use ; Vasodilator Agents ; pharmacology ; therapeutic use

BACKGROUND AND OBJECTIVES: There is increasing evidence to suggest that trimetazidine (TMZ) has the ability to improve ischemic heart failure by way of optimizing the heart's energy metabolism. The aim of this study was to examine the changes of the myocardial enhancement pattern by using two-phase, contrast enhanced, ECG-gated, multi-detector computed tomography (MDCT) after the administration of TMZ in a porcine myocardial infarction model. SUBJECTS AND METHODS: The porcine myocardial infarction model was created by balloon occlusion of the left anterior descending coronary artery. We randomized the swine into two groups: group I (n=7: aspirin only) and group II (n=7: aspirin plus 1 mg/kg TMZ for 4 weeks). Echocardiography and MDCT were performed and the ejection fraction (EF, %), end-systolic volume (ESV, mL) and end-diastolic volume (EDV, mL) were measured at 28 days after induction of myocardial infarction. Three enhancement patterns, including the early arterial phase defect (ED), the 4-min late enhancement (LE) and the residual defect (RD), were also investigated and those were described as class I [ED (-), RD (-), LE (+/-)], class II [ED (+), RD (-), LE (+)], and class III [ED (+), RD (+), LE (+)]. We performed histopathologic examination after sacrificing the animals. RESULTS: The baseline and follow-up echocardiography at 4 weeks after the induction of MI demonstrated no significant differences between the two groups. The LV indices by MDCT were also similar between the two groups (group I: EF, ESV and EDV=46.0+/-12.5%, 35.9+/-23.0 mL and 69.0+/-40.2 mL, respectively, group II: EF, ESV and EDV=49.8+/-13.2%, 43.8+/-23.1 mL and 82.8+/-24.6 mL, respectively, p=NS). The percent wall thickness was similar (69.1+/-19.6% vs. 64.9+/-10.5%, respectively, p=NS), but the enhancement pattern was different between the two groups (group I: class I, II and III=0 (0%), 0 (0%): and 7 (100%) respectively, group II: class I, II and III=0 (0%), 2 (28.6%) and 5 (71.4%), respectively, p<0.001). The volume of tissue that lacked triphenyl tetrazolium chloride was similar between two groups (8.4+/-1.9% vs. 7.3+/-2.6%, respectively, p=NS). CONCLUSION: TMZ administration produced different enhancement patterns on MDCT. This result suggests that TMZ administration can reduce the residual defect in a porcine myocardial infarction model. Although further experiments are needed for determining the effect of TMZ on reducing the irreversible area of infarcted myocardium, this is the first report that proved the beneficial effect of TMZ by performing MDCT.
Animals ; Aspirin ; Balloon Occlusion ; Coronary Vessels ; Echocardiography ; Energy Metabolism ; Follow-Up Studies ; Heart Failure ; Infarction ; Myocardial Infarction* ; Myocardium ; Swine ; Tomography, X-Ray Computed ; Trimetazidine*

No abstract available.
Myocardial Infarction* ; Trimetazidine*