Trimetazidine 20mg tablets

BACKGROUND: Despite maximal treatment, heart failure (HF) remains a major clinical challenge. Besides neurohormonal overactivation, myocardial energy homoeostasis is also impaired in HF. Trimetazidine has the potential to restore myocardial energy status by inhibiting fatty acid oxidation, concomitantly enhancing glucose oxidation. Trimetazidine is an interesting adjunct treatment, for it is safe, easy to use and comes at a low cost. OBJECTIVE: We conducted a systematic review to evaluate all available clinical evidence on trimetazidine in HF. We searched Medline/PubMed, Embase, Cochrane CENTRAL and ClinicalTrials.gov to identify relevant studies. METHODS: Out of 213 records, we included 28 studies in the meta-analysis (containing 2552 unique patients), which almost exclusively randomised patients with HF with reduced ejection fraction (HFrEF). The studies were relatively small (median study size: N=58) and of short duration (mean follow-up: 6 months), with the majority (68%) being open label. RESULTS: Trimetazidine in HFrEF was found to significantly reduce cardiovascular mortality (OR 0.33, 95% CI 0.21 to 0.53) and HF hospitalisations (OR 0.42, 95% CI 0.29 to 0.60). In addition, trimetazidine improved (New York Heart Association) functional class (mean difference: -0.44 (95% CI -0.49 to -0.39), 6 min walk distance (mean difference: +109 m (95% CI 105 to 114 m) and quality of life (standardised mean difference: +0.52 (95% CI 0.32 to 0.71). A similar pattern of effects was observed for both ischaemic and non-ischaemic cardiomyopathy. CONCLUSIONS: Current evidence supports the potential role of trimetazidine in HFrEF, but this is based on multiple smaller trials of varying quality in study design. We recommend a large pragmatic randomised clinical trial to establish the definitive role of trimetazidine in the management of HFrEF.

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Objective: The present systematic review assessed the efficacy of peri-procedurally administered trimetazidine in the prevention of contrast-induced nephropathy (CIN) in patients undergoing coronary interventions with contrast agents. Methods: We performed a systematic literature review of articles published in PubMed and Google Scholar by 7 December 2023 and included articles from the last 15 years that evaluated the efficacy of trimetazidine in preventing CIN in cardiac patients undergoing coronary intervention. Results: After title/abstract and full-text screening, this systematic review included 9 randomized controlled trials (N = 2158 patients) with two groups: Trimetazidine (60–70 mg/day 24 to 48 h before and up to 72 h after the procedure) with hydration and the control group with only hydration. A total of 234/2158 patients developed CIN (Incidence rate [IR], 10.8%) as per the CIN definition of the Contrast Media Safety Committee of the European Society of Urogenital Radiology. The incidence of CIN in the trimetazidine vs. control group was 6.4% (69/1083) vs. 15.4% (165/1075), and the odds ratio (95% CI) was 0.3753 (0.279–0.504). Conclusions: In conclusion, the trimetazidine group had a lower incidence of CIN. Trimetazidine offers a reno-protective effect and helps in reducing the CIN incidence in patients undergoing cardiac intervention. Peri-procedure administration of trimetazidine significantly decreases the risk of CIN in patients despite comorbidities.

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INTRODUCTION: Contrast-induced nephropathy (CIN) is a potential complication associated with the administration of intravenous contrast agents. The objective of this study was to evaluate the effectiveness of remote ischemic preconditioning (RIPC) and two pharmacological interventions in preventing CIN. METHODS: Randomized controlled trials (RCTs) examining the efficacy of RIPC, nicorandil, and trimetazidine in treating CIN were searched within databases such as PubMed, Cochrane Library, Embase, and Web of Science. The primary outcome was the incidence of CIN. The consistency model was used to address heterogeneity and enhance model fit. The assessment of consistency between direct and indirect evidence was conducted through the node-splitting method. Posterior probability estimates and surface under the cumulative ranking area (SUCRA) ranked interventions based on their effectiveness in preventing CIN. The Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) framework was used to grade the quality of evidence. RESULTS: or with a high prevalence of diabetes mellitus. CONCLUSIONS: Nicorandil, trimetazidine, and RIPC all showed renal protective effects. Based on hydration, nicorandil, trimetazidine, and RIPC may show better prophylaxis against CIN than hydration alone after intravenous contrast administration.

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Abstract Aims Impaired myocardial energy homeostasis plays an import role in the pathophysiology of heart failure with preserved ejection fraction (HFpEF). Left ventricular relaxation has a high energy demand, and left ventricular diastolic dysfunction has been related to impaired energy homeostasis. This study investigated whether trimetazidine, a fatty acid oxidation inhibitor, could improve myocardial energy homeostasis and consequently improve exercise haemodynamics in patients with HFpEF. Methods and results The DoPING-HFpEF trial was a phase II single-centre, double-blind, placebo-controlled, randomized cross-over trial. Patients were randomized to trimetazidine treatment or placebo for 3 months and switched after a 2-week wash-out period. The primary endpoint was change in pulmonary capillary wedge pressure, measured with right heart catheterization at multiple stages of bicycling exercise. Secondary endpoint was change in myocardial phosphocreatine/adenosine triphosphate, an index of the myocardial energy status, measured with phosphorus-31 magnetic resonance spectroscopy. The study included 25 patients (10/15 males/females; mean (standard deviation) age, 66 (10) years; body mass index, 29.8 (4.5) kg/m2); with the diagnosis of HFpEF confirmed with (exercise) right heart catheterization either before or during the trial. There was no effect of trimetazidine on the primary outcome pulmonary capillary wedge pressure at multiple levels of exercise (mean change 0 [95% confidence interval, 95% CI −2, 2] mmHg over multiple levels of exercise, P = 0.60). Myocardial phosphocreatine/adenosine triphosphate in the trimetazidine arm was similar to placebo (1.08 [0.76, 1.76] vs. 1.30 [0.95, 1.86], P = 0.08). There was no change by trimetazidine compared with placebo in the exploratory parameters: 6-min walking distance (mean change of −6 [95% CI −18, 7] m vs. −5 [95% CI −22, 22] m, respectively, P = 0.93), N-terminal pro-B-type natriuretic peptide (5 (−156, 166) ng/L vs. −13 (−172, 147) ng/L, P = 0.70), overall quality-of-life (KCCQ and EQ-5D-5L, P = 0.78 and P = 0.51, respectively), parameters for diastolic function measured with echocardiography and cardiac magnetic resonance, or metabolic parameters. Conclusions Trimetazidine did not improve myocardial energy homeostasis and did not improve exercise haemodynamics in patients with HFpEF.

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Background: Pulmonary artery hypertension (PAH) is a chronic and progressive disease. Although current therapy has improved the disease prognosis, PAH has a poor survival rate. The key feature leading to disease progression and death is right ventricular (RV) failure. Methods and results: We assessed the role of trimetazidine, a fatty acid beta-oxidation (FAO) inhibitor, in right ventricular function, remodeling, and functional class in PAH patients, with a placebo-controlled double-blind, case-crossover trial. Twenty-seven PAH subjects were enrolled, randomized, and assigned to trimetazidine or placebo for three months and then reallocated to the other study arm. The primary endpoint was RV morphology and function change after three months of treatment. Secondary endpoints were the change in exercise capacity assessed by a 6 min walk test after three months of treatment and the change in pro-BNP and Galectin-3 plasma levels after three months. Trimetazidine use was safe and well-tolerated. After three months of treatment, patients in the trimetazidine group showed a small but significant reduction of RV diastolic area, and a substantial increase in the 6 min walk distance (418 vs. 438 mt, p = 0.023), without significant changes in biomarkers. Conclusions: A short course of trimetazidine is safe and well-tolerated on PAH patients, and it is associated with significant increases in the 6MWT and minor but significant improvement in RV remodeling. The therapeutic potential of this drug should be evaluated in larger clinical trials.

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We investigated the impact of trimetazidine treatment on left ventricular (LV) functions and cardiac biomarkers in diabetic patients with diastolic dysfunction as an early stage of diabetic cardiomyopathy. Sixty-three patients were randomly assigned to receive either trimetazidine or a placebo for 3 months. At baseline and after 3-months of treatment, measurements of serum levels of glycemic control parameters, lipid profile, tumor necrosis factor alpha, transforming growth factor beta 1, n-terminal pro brain natriuretic peptide and assessment of modified Medical Research Council (mMRC) dyspnea score, echocardiographic indices of LV functions and LV global longitudinal strain (GLS) were performed. After 3-months, trimetazidine group exhibited a significant reduction in left atrial volume index by 6.99% versus an increase by 0.66% in placebo group, p = 0.034. Moreover, average e' increased by a significantly higher percentage in trimetazidine versus placebo group (8.46 ± 18.64 vs. -2.49 ± 14.52, respectively. p = 0.015). Trimetazidine treatment resulted in a significant increase in LVGLS by 6.66% versus LVGLS reduction by 2.79% in placebo group (p = 0.004). Trimetazidine group had a significantly lower median mMRC dyspnea score compared to placebo (0 vs. 1, respectively, p = 0.015) and a significantly lower low-density lipoprotein (LDL-C) (103.43 ± 28.31 vs. 125.34 ± 45.27, respectively, p = 0.032). There was no significant difference between both groups in levels of other biomarkers. Three-months treatment with trimetazidine improved diastolic function parameters, LVGLS, dyspnea severity and LDL-C levels in diabetic patients with diastolic dysfunction.

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Bipolar disorder's core feature is the pathological disturbances in mood, often accompanied by disrupted thinking and behavior. Its complex and heterogeneous etiology implies that a range of inherited and environmental factors are involved. This heterogeneity and poorly understood neurobiology pose significant challenges to existing drug development paradigms, resulting in scarce treatment options, especially for bipolar depression. Therefore, novel approaches are needed to discover new treatment options. In this review, we first highlight the main molecular mechanisms known to be associated with bipolar depression-mitochondrial dysfunction, inflammation and oxidative stress. We then examine the available literature for the effects of trimetazidine in said alterations. Trimetazidine was identified without a priori hypothesis using a gene-expression signature for the effects of a combination of drugs used to treat bipolar disorder and screening a library of off-patent drugs in cultured human neuronal-like cells. Trimetazidine is used to treat angina pectoris for its cytoprotective and metabolic effects (improved glucose utilization for energy production). The preclinical and clinical literature strongly support trimetazidine's potential to treat bipolar depression, having anti-inflammatory and antioxidant properties while normalizing mitochondrial function only when it is compromised. Further, trimetazidine's demonstrated safety and tolerability provide a strong rationale for clinical trials to test its efficacy to treat bipolar depression that could fast-track its repurposing to address such an unmet need as bipolar depression.

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Trimetazidine (TMZ), used for treating stable angina pectoris, has garnered attention in the realm of sports due to its potential performance-enhancing properties, and the World Anti-Doping Agency (WADA) has classified TMZ on the S4 list of prohibited substances since 2014. The purpose of this narrative mini-review is to emphasize the biochemical aspects underlying the abusive use of TMZ among athletes as a metabolic modulator of cardiac energy metabolism. The myocardium's ability to adapt its energy substrate utilization between glucose and fatty acids is crucial for maintaining cardiac function under various conditions, such as rest, moderate exercise, and intense effort. TMZ acts as a partial inhibitor of fatty acid oxidation by inhibiting 3-ketoacyl-CoA thiolase (KAT), shifting energy production from long-chain fatty acids to glucose, reducing oxygen consumption, improving cardiac function, and enhancing exercise capacity. Furthermore, TMZ modulates pyruvate dehydrogenase (PDH) activity, promoting glucose oxidation while lowering lactate production, and ultimately stabilizing myocardial function. TMZs role in reducing oxidative stress is notable, as it activates antioxidant enzymes like glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD). In conclusion, TMZs biochemical mechanisms make it an attractive but controversial option for athletes seeking a competitive edge.

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