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1.
Medicine (Baltimore) ; 98(49): e18238, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31804349

RESUMO

BACKGROUND: Compound danshen dripping pills (CDDP) and trimetazidine (TMZ) are commonly used in the treatment of unstable angina pectoris (UAP). Currently, the combination of CDDP and TMZ has been widely used for UAP. However, the clinical evidence CDDP combined with TMZ for treating UAP is not sufficient. METHODS: We searched for randomized controlled trials testing CDDP combined with TMZ for the treatment of UAP in Chinese National Knowledge Infrastructure database, VIP database, Chinese Biological and Medicine database, Wangfang database, MEDLINE, EMBASE, Cochrane Library, and Web of Science. Extracted data are analyzed using Review Manager 5.3 software. The quality evaluation, forest plots and funnel plots will be conducted by RevMan5.3 software. Moreover, subgroup analysis and sensitivity analysis will also be completed by RevMan5.3. RESULTS: This systematic review will provide powerful clinical evidence of combination CDDP and TMZ for treating UAP. CONCLUSIONS: This systematic review will be provided up-to-date clinical evidence to evaluate the effectiveness and safety of CDDP combined with TMZ for the treatment of parents with UAP.Registration Number: PROSPERO CRD42019143100.


Assuntos
Angina Instável/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Revisão Sistemática como Assunto , Trimetazidina/uso terapêutico , Vasodilatadores/uso terapêutico , Humanos
2.
Zhejiang Da Xue Xue Bao Yi Xue Ban ; 48(3): 282-288, 2019 May 25.
Artigo em Chinês | MEDLINE | ID: mdl-31496160

RESUMO

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 (VE) to late diastolic velocity (VA) ratio (VE/VA) 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 P<0.05); plasma concentration of hr-CRP, TNF-α, angiotensin Ⅱ and endothelin were significantly reduced after trimetazidine treatment, compared with baseline (all P<0.05) and with placebo (all P<0.05). There were no significant differences in any of above parameters after treatment in placebo group (all P>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.


Assuntos
Complicações do Diabetes , Diabetes Mellitus , Tolerância ao Exercício , Coração , Hipertensão , Trimetazidina , Complicações do Diabetes/complicações , Diabetes Mellitus/tratamento farmacológico , Método Duplo-Cego , Tolerância ao Exercício/efeitos dos fármacos , Coração/efeitos dos fármacos , Humanos , Hipertensão/complicações , Hipertensão/tratamento farmacológico , Peptídeo Natriurético Encefálico/sangue , Estudos Prospectivos , Resultado do Tratamento , Trimetazidina/farmacologia , Trimetazidina/uso terapêutico , Vasodilatadores/farmacologia , Vasodilatadores/uso terapêutico
3.
Niger J Clin Pract ; 22(7): 997-1001, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31293267

RESUMO

Background: In this study, postoperative cardiac functions were observed in patients undergoing coronary artery bypass grafting (CABG) surgery following preoperative administration of the anti-ischemic drug trimetazidine. Materials and Methods: The study included a total of 50 CABG patients; 25 were administered with trimetazidine preoperatively and 25 did not receive trimetazidine. A retrospective evaluation was made of the parameters of age, gender, preoperative echocardiography (ECHO) results, cross-clamping durations, postoperative inotropic requirements, and postoperative 4th-h troponin-I levels and the groups were compared. Results: There was no statistically significant difference determined between the 2 groups in respect of the data of age, gender, comorbidity, preoperative ECHO signs [(ejection fraction (EF), left ventricle end systolic diameter (lvsd), left ventricle end diastolic diameter (lvdd), left atrium diameter (LA), and intraventricular septum thickness (IVS)], inotropic requirements, and postoperative troponin-I levels. In the control group, a positive correlation was determined between postoperative troponin-I levels and DM (r: 0.597, p: 0.002). There was no correlation determined in the trimetazidine group (r:-0.042, p: 0.844). Conclusion: The results of this study demonstrated a positive correlation between postoperative troponin-I levels and DM in the group not administered with trimetazidine. There was no such correlation determined in the group administered with trimetazidine. This result may suggest that DM may increase troponin-I levels in the absence of trimetazidine, and therefore that the drug may be cardioprotective in such cases. Further studies on more extensive patient populations are required to confirm these results.


Assuntos
Ponte de Artéria Coronária , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Cuidados Pré-Operatórios , Trimetazidina/administração & dosagem , Trimetazidina/uso terapêutico , Troponina T/sangue , Vasodilatadores/uso terapêutico , Idoso , Ponte de Artéria Coronária/métodos , Feminino , Hemodinâmica , Humanos , Masculino , Pessoa de Meia-Idade , Traumatismo por Reperfusão Miocárdica/fisiopatologia , Período Pós-Operatório , Período Pré-Operatório , Estudos Retrospectivos
4.
Chin Med J (Engl) ; 132(12): 1461-1466, 2019 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-31205105

RESUMO

BACKGROUND: Low handgrip strength (HS) and declining gait speed (GS) are increasingly obvious with aging, requiring effective, and safe medication for treatment. Trimetazidine (TMZ) modified release tablets, a common anti-angina drug, has potential benefits for alleviating the condition, but this has not yet been fully studied and therefore is the aim of this study. METHODS: This is a prospective randomized controlled study. Fifty-eight eligible patients will be randomly assigned to one of two study groups: TMZ group or control group. For the TMZ group, a dose of 35 mg of oral TMZ will be administered with a meal twice a day for 3 months, in addition to any conventional treatments for angina. Only conventional treatments for angina will be administrated in the control group. The primary outcome will be the 6-min walking distance and the secondary outcomes will be: muscle strength (HS and pinch strength), GS, muscle endurance (five times sit-to-stand test), balance maintenance (tandem standing test), and the frequency of angina per week. Additionally, body mass index, circumferences (biceps, waist, hip, and calf), albumin levels, and the score on a five-question scale for sarcopenia will be obtained during the study. DISCUSSION: This study aims to evaluate the usefulness of TMZ in a population with poor muscle function. The results may provide an effective and safe medical treatment to people with low muscle strength or physical performance. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR1800015000; www.chictr.org.cn/showproj.aspx?proj=25445.


Assuntos
Angina Estável/tratamento farmacológico , Músculo Esquelético/efeitos dos fármacos , Trimetazidina/uso terapêutico , Vasodilatadores/uso terapêutico , Idoso , Angina Estável/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Resultado do Tratamento
5.
Iran J Kidney Dis ; 13(3): 191-197, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-31209192

RESUMO

INTRODUCTION: Contrast-induced Acute Kidney Injury (CI-AKI) is a prevalent complication of chronic kidney disease (CKD) patients. The aim of this study was to evaluate the effects of periprocedural administration of trimetazidine as an anti-oxidant agent on the incidence of CI-AKI in CKD patients based on changes of Neutrophil Gelatinase-Associated Lipocalin (uNGAL) level, which has recently been introduced as an early predictor of CI-AKI. METHODS: One hundred CKD patients with a mean GFR of 50 ± 7 cc/min who were candidate for coronary angiography assigned randomly to receive (50 patients, intervention group) or not receive (50 patients, control group) trimetazidine (70mg/d) for 72 hours. CI-AKI was defined as 0.5 mg or 25% increase in serum creatinine. We also checked uNGAL before and 12h after angiography. RESULTS: Serum creatinine, showed a trend of less increment in the case group, although could not achieve a significant difference, there was a significant difference in urinary NGAL rise between two groups. CI-AKI was defined as 1.7 times increase in uNGAL level (12h after angiography to pre-procedurally uNGAL level ratio) according to the ROC curves. The incidence of CI-AKI according to urinary NGAL definition was 8% in the Trimetazidine group and 24% in the control group (P < .05). CONCLUSION: We concluded that Trimetazidine treatment before angiography may be effective in CI-AKI prevention. Moreover, it is shown that 1.7 times increase in urine NGAL after angiography is a valuable cut off point for clinicians to discriminate high risk patients for contrast nephropathy.


Assuntos
Lesão Renal Aguda/prevenção & controle , Meios de Contraste/efeitos adversos , Lipocalina-2/urina , Insuficiência Renal Crônica/complicações , Trimetazidina/uso terapêutico , Lesão Renal Aguda/induzido quimicamente , Idoso , Biomarcadores/urina , Angiografia Coronária/efeitos adversos , Creatinina/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Curva ROC , Método Simples-Cego
6.
Biomed Pharmacother ; 116: 109003, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31125823

RESUMO

Trimetazidine (TMZ) has been shown to optimize myocardial energy metabolism and is a common anti-ischemic agent. Our trial (ChiCTR-TRC-13003298) aimed to explore whether TMZ has any preventive effect on high-altitude fatigue (HAF), cardiac function and cardiorespiratory fitness upon acute high-altitude exposure and how it works on HAF. Thirty-nine healthy young subjects were enrolled in a randomized double-blinded placebo-controlled trial and were randomized to take oral TMZ (n = 20) or placebo (n = 19), 20 mg tid, 14 days prior to departure until the end of study. The 2018 Lake Louise Score questionnaire, echocardiography, assessments of physical working capacity, circulating markers of myocardial energy metabolism and fatigue were performed both before departure and arrival at highland. At follow-up, TMZ significantly reduced the incidence of HAF (p = 0.038), reversed cardiorespiratory fitness impairment, decreased left ventricular end-systolic volume (LVESV, p = 0.032) and enhanced left ventricular ejection fraction (LVEF, p = 0.015) at highland. Relative to the placebo group, the TMZ group had significantly lower LDH (p = 0.025) and lactate levels before (p < 0.001) and after (p = 0.012) physical exercise after acute high-altitude exposure. Additionally, improved left ventricular systolic function might have contributed to ameliorating HAF during TMZ treatment (LVEF, OR = 0.859, 95% CI = 0.741-0.996, p = 0.044). In conclusion, our results demonstrated that TMZ could prevent HAF, cardiorespiratory fitness impairment and improves left ventricular systolic function during acute high-altitude exposure. This trial provides new insights into the effect of TMZ and novel evidence against HAF and cardiorespiratory fitness impairment at highland.


Assuntos
Altitude , Aptidão Cardiorrespiratória/fisiologia , Fadiga/tratamento farmacológico , Fadiga/fisiopatologia , Trimetazidina/uso terapêutico , Adolescente , Doença da Altitude/sangue , Doença da Altitude/tratamento farmacológico , Doença da Altitude/epidemiologia , Doença da Altitude/fisiopatologia , Método Duplo-Cego , Metabolismo Energético/efeitos dos fármacos , Fadiga/sangue , Testes de Função Cardíaca , Humanos , Incidência , L-Lactato Desidrogenase/sangue , Lactatos/sangue , Miocárdio/metabolismo , Placebos , Análise de Regressão , Sístole/efeitos dos fármacos , Trimetazidina/farmacologia , Função Ventricular Esquerda/efeitos dos fármacos , Adulto Jovem
7.
J Pharmacol Sci ; 139(4): 311-318, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30962089

RESUMO

Diabetic cardiomyopathy (DCM) is characterized by cardiac hypertrophy, fibrosis, oxidative stress and inflammation. Trimetazidine (TMZ), a potent metabolism modulator, has been shown to be cardioprotective in experimental models of ischaemia-reperfusion and type 2 diabetes-induced cardiomyopathy. The present study examined whether TMZ inhibits cardiomyopathy induced by insulin-dependent type 1 diabetes. Wistar rats were randomly divided into control group (vehicle alone), diabetes mellitus (DM; induced by streptozocin (STZ) injection) group and DM treated with TMZ (DM/TMZ) group. Cardiac function, histology, plasma biochemistry and molecular mechanism were assessed. STZ induced diabetes in rats as indicated by hyperglycemia, increased and decreased levels of advanced glycation end products (AGEs) and insulin respectively. Diabetic rats were characterized by left ventricular dysfunction, cardiachypertrophy and fibrosis and signs of inflammation and oxidative stress in the myocardium, which were accompanied by elevated levels of NADPH oxidase 2 (Nox2) and transient receptor potential channel 3 (TRPC3) in the heart. TMZ treatment ameliorated diabetes-associated structural and functional alterations by inhibiting Nox2 and TRPC3 without having any effects on glucose, insulin and AGEs levels. These results suggest that TMZ could be used as a therapy to treat cardiomyopathy associated with type 1 induced diabetes mellitus.


Assuntos
Cardiotônicos/uso terapêutico , Cardiomiopatias Diabéticas/prevenção & controle , NADPH Oxidase 2/antagonistas & inibidores , Estresse Oxidativo/efeitos dos fármacos , Canais de Cátion TRPC/antagonistas & inibidores , Trimetazidina/uso terapêutico , Animais , Diabetes Mellitus Tipo 1/complicações , Cardiomiopatias Diabéticas/etiologia , Cardiomiopatias Diabéticas/genética , Modelos Animais de Doenças , Masculino , Terapia de Alvo Molecular , Ratos Wistar , Trimetazidina/farmacologia
8.
Neuroepidemiology ; 52(3-4): 220-226, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30831572

RESUMO

BACKGROUND: The prevalence of drug-induced parkinsonism (DIP) has been reported with the use of trimetazidine (TMZ), an antianginal medication available in Asian and European countries. Very few studies have evaluated the association between DIP and TMZ use, and studies using population-based data from national databases are lacking. OBJECTIVES: To investigate the association between DIP and use of TMZ in patients with angina using data from a national healthcare claims database and to determine the predictive factors of DIP in TMZ use. METHODS: A cross-sectional study was conducted on patients aged 40 years or more diagnosed with angina, using the Korean National Healthcare claims 2014 database. The association between TMZ use and DIP was evaluated using multivariate logistic regression analysis, adjusting for confounders, including age; sex; insurance type; comorbidities; and concurrent medications known to be commonly associated with DIP, such as typical and atypical antipsychotics. RESULTS: Of the patients included in the study, 19% were prescribed TMZ. In addition, 2.5% of TMZ users had preexisting extrapyramidal and movement disorders. TMZ use was found to be a significant predictor of a new diagnosis of parkinsonism (adjusted OR [aOR] 1.39; 95% CI 1.06-1.81; p = 0.016). Age ≥65 years (aOR 2.07; 95% CI 1.13- 3.74; p = 0.017) and stroke as comorbid disease (aOR 3.23; 95% CI 1.87-5.61; p < 0.001) were also significantly associated with a new diagnosis of parkinsonism in TMZ users. CONCLUSIONS: Treatment with TMZ was a statistically significant predictor of a new diagnosis of parkinsonism. Efforts should focus on close monitoring of, and education on, TMZ use in relation to DIP in all patients who are prescribed TMZ, including those with preexisting extrapyramidal and movement disorders.


Assuntos
Transtornos Parkinsonianos/induzido quimicamente , Transtornos Parkinsonianos/epidemiologia , Vigilância da População , Trimetazidina/efeitos adversos , Trimetazidina/uso terapêutico , Vasodilatadores/efeitos adversos , Adulto , Idoso , Angina Instável/tratamento farmacológico , Angina Instável/epidemiologia , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Transtornos Parkinsonianos/diagnóstico , Vigilância da População/métodos , República da Coreia/epidemiologia , Vasodilatadores/uso terapêutico
9.
JAMA Cardiol ; 4(3): 230-235, 2019 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-30725091

RESUMO

Importance: Hypertrophic cardiomyopathy causes limiting symptoms in patients, mediated partly through inefficient myocardial energy use. There is conflicting evidence for therapy with inhibitors of myocardial fatty acid metabolism in patients with nonobstructive hypertrophic cardiomyopathy. Objective: To determine the effect of oral therapy with trimetazidine, a direct inhibitor of fatty acid ß-oxidation, on exercise capacity in patients with symptomatic nonobstructive hypertrophic cardiomyopathy. Design, Setting, and Participants: This randomized, placebo-controlled, double-blind clinical trial at The Heart Hospital, University College London Hospitals, London, United Kingdom was performed between May 31, 2012, and September 8, 2014. The trial included 51 drug-refractory symptomatic (New York Heart Association class ≥2) patients aged 24 to 74 years with a maximum left ventricular outflow tract gradient 50 mm Hg or lower and a peak oxygen consumption during exercise of 80% or less predicted value for age and sex. Statistical analysis was performed from March 1, 2016 through July 4, 2018. Interventions: Participants were randomly assigned to trimetazidine, 20 mg, 3 times daily (n = 27) or placebo (n = 24) for 3 months. Main Outcomes and Measures: The primary end point was peak oxygen consumption during upright bicycle ergometry. Secondary end points were 6-minute walk distance, quality of life (Minnesota Living with Heart Failure questionnaire), frequency of ventricular ectopic beats, diastolic function, serum N-terminal pro-brain natriuretic peptide level, and troponin T level. Results: Of 49 participants who received trimetazidine (n = 26) or placebo (n = 23) and completed the study, 34 (70%) were male; the mean (SD) age was 50 (13) years. Trimetazidine therapy did not improve exercise capacity, with patients in the trimetazidine group walking 38.4 m (95% CI, 5.13 to 71.70 m) less than patients in the placebo group at 3 months after adjustment for their baseline walking distance measurements. After adjustment for baseline values, peak oxygen consumption was 1.35 mL/kg per minute lower (95% CI, -2.58 to -0.11 mL/kg per minute; P = .03) in the intervention group after 3 months. Conclusions and Relevance: In symptomatic patients with nonobstructive hypertrophic cardiomyopathy, trimetazidine therapy does not improve exercise capacity. Pharmacologic therapy for this disease remains limited. Trial Registration: ClinicalTrials.gov identifier: NCT01696370.


Assuntos
Cardiomiopatia Hipertrófica/tratamento farmacológico , Tolerância ao Exercício/efeitos dos fármacos , Miocárdio/metabolismo , Trimetazidina/uso terapêutico , Vasodilatadores/uso terapêutico , Administração Oral , Adulto , Idoso , Cardiomiopatia Hipertrófica/fisiopatologia , Ácidos Graxos/metabolismo , Feminino , Insuficiência Cardíaca/metabolismo , Insuficiência Cardíaca/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Mordida Aberta/patologia , Consumo de Oxigênio/efeitos dos fármacos , Qualidade de Vida , Trimetazidina/administração & dosagem , Reino Unido/epidemiologia , Vasodilatadores/administração & dosagem
10.
Mymensingh Med J ; 28(1): 114-119, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30755559

RESUMO

Ischaemic cardiomyopathy (ICM) remains a major health problem, both in developed and developing countries like Bangladesh where it causes a significant number of morbidity and mortality. The treatment and outcome of ICM chiefly depends on the presence and extent of hibernating myocardium. In this regard addressing anginal symptoms is the key to patients' comfort as well to achieving the goal of treatment. Glyceryl trinitrate (GTN) and trimetazidine (TMZ) are two widely used drugs for relieving angina. This pilot study was designed to answer some of the confusions and controversies regarding their use and to bring precision in decision making in the treatment of ICM. Here, comparison of GTN and trimetazidine were done by assessing the symptoms by NYHA and CCS class following their use in ICM patients, admitted in Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, Bangladesh from 15th October, 2015 to 15th April, 2016, who were randomly placed in two groups in a prospective manner. Most of the patients were in age group 51-60 years and were male in both the groups. It was observed that there was no significant difference in NYHA and CCS class at base line and at discharge between two groups (p>0.05). But statistically significant (p<0.05), improvement noted at 6 weeks and 12 weeks in GTN group in comparison to trimetazidine group. GTN stood out to be a better option than TMZ in the treatment of ICM. Moreover GTN is a cheaper option than TMZ.


Assuntos
Cardiomiopatias/tratamento farmacológico , Contração Miocárdica/efeitos dos fármacos , Isquemia Miocárdica/tratamento farmacológico , Isquemia Miocárdica/fisiopatologia , Nitroglicerina/uso terapêutico , Trimetazidina/uso terapêutico , Vasodilatadores/uso terapêutico , Bangladesh , Humanos , Masculino , Projetos Piloto , Estudos Prospectivos , Resultado do Tratamento
11.
Am Heart J ; 210: 98-107, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30771737

RESUMO

BACKGROUND: About 30% of angina patients have persisting symptoms despite successful revascularization and antianginal therapy. Moreover, in stable patients, percutaneous coronary intervention (PCI) does not improve survival as compared with medical therapy alone. Trimetazidine, an antianginal agent devoid of hemodynamic effect, may help reducing symptoms and improving outcomes after PCI. The ATPCI study is investigating the efficacy and safety of adding trimetazidine to standard-of-care in angina patients who had a recent PCI. METHODS: ATPCI is a randomized, double-blind, parallel-group, placebo-controlled, event-driven study in patients with coronary artery disease having undergone PCI because of stable angina (elective PCI) or unstable angina/NSTEMI (urgent PCI). After PCI, patients were randomized to trimetazidine (35 mg bid) or placebo on top of standard-of-care including event prevention drugs and antianginal treatment. Patients will be followed for 2 to 4 years. The primary efficacy endpoint is a composite of cardiac death, hospitalization for a cardiac event and recurrence or persistence of angina. Safety events related to trimetazidine use will be monitored. RESULTS: Recruitment lasted from September 2014 to June 2016. A total of 6007 patients were enrolled (58% and 42% after elective and urgent PCI, respectively). Mean age was 61 years, 77% were males, and median durations of coronary artery disease were 1 and 5 months (if urgent or elective PCI, respectively). Almost all patients received drugs for event prevention and antianginal therapy at baseline. CONCLUSION: The ATPCI study will shed further light on the management of contemporary angina patients after PCI. Results are expected in 2019.


Assuntos
Angina Pectoris/tratamento farmacológico , Intervenção Coronária Percutânea , Complicações Pós-Operatórias/tratamento farmacológico , Trimetazidina/uso terapêutico , Vasodilatadores/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Angina Pectoris/cirurgia , Doença da Artéria Coronariana/cirurgia , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Placebos/uso terapêutico , Recidiva , Trimetazidina/efeitos adversos , Vasodilatadores/efeitos adversos , Adulto Jovem
12.
J Clin Pharm Ther ; 44(3): 400-408, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30659627

RESUMO

WHAT IS KNOWN AND OBJECTIVE: The approved indication for trimetazidine (TMZ) was restricted to "add-on therapy for the symptomatic treatment of patients with stable angina pectoris who are inadequately controlled by or intolerant to first-line antianginal therapies" in 2012 by the Committee for Medicinal Products for Human Use (CHMP). TMZ was no longer indicated for ophthalmology and otolaryngology (ENT) indications. This drug utilization study analysed actual utilization of TMZ before and after the restriction on its indications to evaluate the effectiveness of risk minimization measures (RMM). METHODS: This was a multi-national, cross-sectional, non-interventional drug utilization study using European databases: IMS Prescribing Insights (PI) for France and Spain, National Diagnostic Index (NDI) for Romania and National Prescription Audit (NPA) for Hungary. TMZ prescriptions issued by Ear-Nose-Throat (ENT) specialists, ophthalmologists, cardiologists and General Physicians (GPs)/others were analysed during the 24-month period before (reference period) and after RMM implementation (assessment period). RESULTS AND DISCUSSION: During the assessment period, most of the TMZ prescriptions for ENT and ophthalmology indications (un-authorized indications) were made by GPs/others followed by ENT specialists, ophthalmologists and cardiologists in most of the countries. The proportion of TMZ prescriptions for ENT or ophthalmological indications after the restrictions on indication was reduced in Hungary (by 0.4%) and Spain (by 11.8%), remained the same in Romania and increased in France (by 3.7%). WHAT IS NEW AND CONCLUSION: This study showed that a significant proportion of TMZ prescriptions was off-label for ENT or ophthalmological indications following the RMM implementation. More effective RMM strategies are required to reduce off-label prescriptions of TMZ.


Assuntos
Angina Estável/tratamento farmacológico , Trimetazidina/uso terapêutico , Vasodilatadores/uso terapêutico , Estudos Transversais , Uso de Medicamentos , França , Humanos , Hungria , Romênia , Espanha
13.
Angiology ; 70(4): 291-298, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29888611

RESUMO

Trimetazidine (TMZ) is a metabolic agent with significant anti-ischemic properties. By inhibiting the terminal enzyme in the ß-oxidation pathway, it shifts the energy substrate metabolism, enhancing glucose metabolism. Thus, it maintains the required energy production with less oxygen consumption, an effect necessary in cases of myocardi. Trimetazidine was recently reaccredited as add-on therapy for symptomatic treatment in patients with stable angina, not adequately controlled or intolerant to first-line therapy. Trimetazidine was included in the European Society of Cardioloy 2013 guidelines for the management of stable coronary artery disease. Although TMZ has been used in cardiology for >40 years, only a few studies have assessed its effects in patients with acute ischemic conditions. This review summarizes the current literature regarding the addition of TMZ in patients with acute ischemic conditions (acute myocardial infarction, ST-segment elevation myocardial infarction, non-ST-segment elevation myocardial infarction, percutaneous coronary intervention, and coronary artery bypass grafting). There is growing evidence from recent studies that the addition of TMZ in patients with such conditions is beneficial in terms of myocardial damage and major cardiac events as well as decreasing reperfusion injury and contrast-induced nephropathy.


Assuntos
Lesão Renal Aguda/prevenção & controle , Fármacos Cardiovasculares/uso terapêutico , Metabolismo Energético/efeitos dos fármacos , Glucose/metabolismo , Rim/efeitos dos fármacos , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Miócitos Cardíacos/efeitos dos fármacos , Trimetazidina/uso terapêutico , Lesão Renal Aguda/induzido quimicamente , Lesão Renal Aguda/metabolismo , Lesão Renal Aguda/patologia , Animais , Fármacos Cardiovasculares/efeitos adversos , Meios de Contraste/administração & dosagem , Ponte de Artéria Coronária/efeitos adversos , Humanos , Rim/metabolismo , Rim/patologia , Traumatismo por Reperfusão Miocárdica/etiologia , Traumatismo por Reperfusão Miocárdica/metabolismo , Traumatismo por Reperfusão Miocárdica/patologia , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/patologia , Intervenção Coronária Percutânea/efeitos adversos , Fatores de Risco , Resultado do Tratamento , Trimetazidina/efeitos adversos
14.
Medicine (Baltimore) ; 97(51): e13580, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30572460

RESUMO

BACKGROUND: Shexiang Baoxin Pill (SBP) is one of the most commonly used traditional Chinese patent medicines for cardiovascular diseases. This systematic review was designed to provide rigorous therapeutic efficacy and safety evidence on the use of SBP combined with trimetazidine in elderly patients with heart failure (HF) secondary to ischaemic cardiomyopathy (ICM). METHODS: Relevant randomized controlled trials (RCTs) investigating the clinical efficacy of SBP combined with trimetazidine in treating ICM-associated HF were widely searched in electronic databases, including PubMed, Cochrane library, EMBASE, CBM, CNKI, VMIS, and Wanfang up to January 1, 2018. The methodological quality of each trial was assessed according to the Cochrane Reviewers' Handbook 5.0. Meta-analysis was performed by using Review Manager 5.3. RESULTS: Eighteen RCTs (N = 1532) that met the criteria were included in the review for the assessment of methodological quality. Meta-analysis showed that, when compared with conventional therapy, SBP combined with trimetazidine significantly improved the clinical efficacy and indices of cardiac function (including increasing left ventricular ejection fraction [LVEF] and 6-minute walk distance [6-MWD], decreasing left ventricular end-diastolic diameter [LVEDD] and left ventricular end-systolic diameter [LVESD]) without serious adverse reactions. CONCLUSION: This work provides evidence of the benefit of SBP combined with trimetazidine for the treatment of HF secondary to ICM. More high quality and well-designed RCTs are needed to confirm these findings.


Assuntos
Fármacos Cardiovasculares/uso terapêutico , Medicamentos de Ervas Chinesas/uso terapêutico , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/etiologia , Isquemia Miocárdica/complicações , Trimetazidina/uso terapêutico , Quimioterapia Combinada , Humanos , Isquemia Miocárdica/tratamento farmacológico , Ensaios Clínicos Controlados Aleatórios como Assunto
15.
Orv Hetil ; 159(38): 1549-1555, 2018 Sep.
Artigo em Húngaro | MEDLINE | ID: mdl-30227735

RESUMO

INTRODUCTION: The effectiveness of the manegement of stable coronary artery disease among outpatients is not well known. AIM: The aim of the study was to evaluate the effect of daily once trimetazidine prolong 80 mg on the angina number and severity (Canadian Cardiovascular Society class). METHOD: This multicenter, prospective, observational, 3-month clinical study included 2160 patients, but only 1701 patients completed the study. The patients' mean age was 68 years (17% under 60 years). The start of angina was 7.8 ± 6.7 years. Hypertension (93.4%) and hypercholesterolemia (81%) were very common. RESULTS: The patients were well treated with beta-blocking agents (88%), calcium antagonists (49%), angiotensin-converting enzym inhibitors (90%) and statin (77%) but only 5% received ivabradine and 50.5% was treated with trimetazidine MR. The patients attended 3 visits (inclusion, 1 month, 3 month). During the 3-month period, the weekly angina number of all patients treated with trimetazidine prolong 80 mg decreased from 2.55 to 0.41 (p<0.0001). A favorable effect was observed in CCS grading: CCS I. from 40.37% to 66.81%, CCS II. from 49.89% to 30.59%, CCS III. from 9.17% to 2% and CCS IV. from 0.56% to 0%. The mean office measured blood pressure decreased from 137/83 mmHg to 130/80 mmHg and the heart rate from 74 bpm to 71 bpm. CONCLUSIONS: In the real-life, in the stable coronary artery disease the angina remains despite the medical treatment. Once a day administered trimetazidine prolong 80 mg significantly reduced the weekly number of angina and the severity, too. These beneficial effects mediated not only by antiischemic effect but also by increased medication adherence. Orv Hetil. 2018; 159(38): 1549-1555.


Assuntos
Angina Estável/tratamento farmacológico , Índice de Gravidade de Doença , Trimetazidina/uso terapêutico , Vasodilatadores/uso terapêutico , Idoso , Angina Estável/fisiopatologia , Pressão Sanguínea/efeitos dos fármacos , Feminino , Humanos , Masculino , Adesão à Medicação , Pessoa de Meia-Idade , Estudos Prospectivos , Resultado do Tratamento
16.
Front Immunol ; 9: 2015, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30233596

RESUMO

Aims: Cardiac dysfunction can be a fatal complication during severe sepsis. The migration of neutrophils is significantly impaired during severe sepsis. We sought to determine the role of trimetazidine (TMZ) in regulation of neutrophil migration to the heart in a mouse model of sepsis and endotoxemia, and to identify the mechanism whereby TMZ confers a survival advantage. Methods and Results: C57/BL6 mice were (1) injected with LPS followed by 24-h TMZ administration, or (2) treated with TMZ (20 mg/kg/day) for 1 week post cecal ligation and puncture (CLP) operation. Echocardiography and Millar system detection showed that TMZ alleviated cardiac dysfunction and histological staining showed the failure of neutrophils migration to heart in both LPS- and CLP-induced mice. Bone marrow transplantation revealed that TMZ-pretreated bone marrow cells improved LPS- and CLP-induced myocardial dysfunction and enhanced neutrophil recruitment in heart. In CXCL2-mediated chemotaxis assays, TMZ increased neutrophils migration via AMPK/Nrf2-dependent up-regulation of CXCR2 and inhibition of GRK2. Furthermore, using luciferase reporter gene and chromatin immunoprecipitation assays, we found that TMZ promoted the binding of the Nrf2 and CXCR2 promoter regions directly. Application of CXCR2 inhibitor completely reversed the protective effects of TMZ in vivo. Co-culture of neutrophils and cardiomyocytes further validated that TMZ decreased LPS-induced cardiomyocyte pyroptosis by targeting neutrophils. Conclusion: Our findings suggested TMZ as a potential therapeutic agent for septic or endotoxemia associated cardiac dysfunction in mice. STUDY HIGHLIGHTS  What is the current knowledge on the topic? Migration of neutrophils is significantly impaired during severe sepsis, but the underlying mechanisms remain unknown. What question did this study address? The effects of TMZ on cardiac dysfunction via neutrophils migration. What this study adds to our knowledge TMZ attenuated LPS-induced cardiomyocyte pyroptosis and cardiac dysfunction by promoting neutrophils recruitment to the heart tissues via CXCR2. How this might change clinical pharmacology or translational science Our findings suggested TMZ as a potential therapeutic agent for septic cardiac dysfunction.


Assuntos
Endotoxemia/tratamento farmacológico , Insuficiência Cardíaca/prevenção & controle , Neutrófilos/imunologia , Sepse/tratamento farmacológico , Trimetazidina/uso terapêutico , Vasodilatadores/uso terapêutico , Adenilato Quinase/metabolismo , Animais , Ceco/cirurgia , Células Cultivadas , Quimiocina CXCL2/metabolismo , Quimiotaxia , Modelos Animais de Doenças , Endotoxemia/imunologia , Insuficiência Cardíaca/imunologia , Humanos , Lipopolissacarídeos/imunologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Fator 2 Relacionado a NF-E2/metabolismo , Neutrófilos/efeitos dos fármacos , Sepse/imunologia , Transdução de Sinais
17.
Adv Ther ; 35(9): 1368-1377, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-30105656

RESUMO

INTRODUCTION: Trimetazidine (TMZ) was shown to reduce angina symptoms and increase the exercise capacity in stable angina (SA) patients. A new formulation allowing a once-daily (od) dosage could improve patients' satisfaction and adherence. METHODS: ODA was a 3-month, observational, multicenter, prospective Russian study in SA patients with persistent symptoms despite therapy. Angina attack frequency, short-acting nitrate (SAN) consumption, adherence to antianginal medications, and overall efficacy and tolerability of TMZ 80 mg od were assessed in a real-world setting. RESULTS: A total of 3066 patients were included (mean age 62.8, 48% male). After 3 months, TMZ 80 mg od treatment led to a significant (p < 0.001) decrease in angina attack frequency (from 4.7 ± 3.5 to 0.9 ± 1.3/week) and SAN use (from 4.5 ± 3.9 to 0.7 ± 1.3/week). Overall tolerability and effectiveness were rated as "very good" by the majority of physicians. Medication adherence improved significantly, with good adherence reported by 56% of patients (vs. 24% at baseline, p < 0.0001) and non-adherence by 3% (vs. 36% at baseline, p < 0.0001) at month 3. Patient satisfaction with TMZ od was 9.5 [on a scale of 1 to 10 (very satisfied)]. Patients reported improved physical activity: more patients reported no limitations (15% vs. 1% at baseline p < 0.01), slight limitation (46% vs. 5% at baseline, p < 0.001) or moderate limitation (30% vs. 23%, p < 0.01) and fewer patients reported substantial limitation (8% vs. 52% at baseline, p < 0.001) or very marked reduction (1% vs. 19% at baseline, p < 0.01) at month 3. CONCLUSION: In this prospective, observational study, TMZ 80 mg od effectively reduced angina attacks and SAN consumption, improved physical activity and adherence and was well tolerated in chronic SA patients. TRIAL REGISTRATION: ISRCTN registry Identifier, ISRCTN97780949. FUNDING: Servier. Plain language summary available for this article.


Assuntos
Angina Estável/tratamento farmacológico , Trimetazidina/uso terapêutico , Vasodilatadores/uso terapêutico , Idoso , Preparações de Ação Retardada , Feminino , Humanos , Masculino , Adesão à Medicação , Pessoa de Meia-Idade , Satisfação do Paciente , Estudos Prospectivos , Federação Russa , Trimetazidina/administração & dosagem , Trimetazidina/efeitos adversos , Vasodilatadores/administração & dosagem , Vasodilatadores/efeitos adversos
18.
Oxid Med Cell Longev ; 2018: 1072805, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30057668

RESUMO

Even after recovery from acute kidney injury, glomeruli remain vulnerable to further injury by way of interstitial fibrosis. This study is aimed at elucidating the effects of post ischemia-reperfusion (I/R) treatment with trimetazidine on the progression to renal fibrosis as well as short- and intermediate-term aspects. Trimetazidine 3 mg/kg or 0.9% saline was given intraperitoneally once upon reperfusion or daily thereafter for 5 d or 8 w. Renal histologic changes and related signaling proteins were assessed. After 24 h, post I/R treatment with trimetazidine significantly reduced serum blood urea nitrogen and creatinine levels and tubular injury accompanied with upregulation of hypoxia-inducible factor- (HIF-) 1α, vascular endothelial growth factor (VEGF), and Bcl-2 expression. After 5 d, post I/R treatment with trimetazidine reduced renal tubular cell necrosis and apoptosis with upregulation of HIF-1α-VEGF and tissue inhibitors of metalloproteinase activities, attenuation of matrix metalloproteinase activities, and alteration of the ratio of Bax to Bcl-2 levels. After 8 w, however, post I/R treatment with trimetazidine did not modify the progression of renal fibrosis. In conclusion, post I/R treatment with trimetazidine allows ischemic kidneys to regain renal function and structure more rapidly compared to nontreated kidneys, but not enough to resolute renal fibrosis in long-term aspect.


Assuntos
Lesão Renal Aguda/tratamento farmacológico , Lesão Renal Aguda/metabolismo , Fibrose/tratamento farmacológico , Fibrose/metabolismo , Isquemia/tratamento farmacológico , Traumatismo por Reperfusão/tratamento farmacológico , Trimetazidina/uso terapêutico , Animais , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Immunoblotting , Isquemia/metabolismo , Rim/efeitos dos fármacos , Rim/metabolismo , Rim/patologia , Masculino , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Ratos , Ratos Sprague-Dawley , Traumatismo por Reperfusão/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Proteína X Associada a bcl-2/metabolismo
19.
Med Glas (Zenica) ; 15(2): 109-114, 2018 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-30047538

RESUMO

Aim To investigate whether or not additional treatment of ischemic heart disease with trimetazidine could improve effort tolerance and overall quality of life of patients with ischemic heart disease. Methods The study included 200 patients with ischemic heart disease. The sample was divided into 2 randomly selected groups: experimental and control group. The diagnostic procedures included: trade-mill test according to Bruce protocol, heart ultrasound for assessment of ejection fraction, test for the assessment of quality of life and subjective problems (Short Form SF 36). Patients were tested for time of discharge from hospital, after 6 and 12 months, including re-evaluation of the overall condition of the previous period. Results Patients have been tested for the tolerance of effort with the measurement Metabolic Equivalent of TASK (METs), which is the equivalent of physical labor. Patients treated with trimetazidine since the time of hospital discharge achieved an average of 3.68, after 6 months 5.68, and after 12 months 7.79 METs. The control group achieved 3.68, 3.59 and 3.87 METs, respectively. Using Mann-Whitney test no difference at discharge time (p=0.880), but after six and twelve months there was some difference (p<0.001). Results of ejection fraction measured by echocardiography were similar. No difference between the two groups with regard to time of discharge (p=0.821, but p<0.001 after six and twelve months, respectively). Conclusion Patients treated with conventional therapy including trimetazidine have better tolerance to effort and better ejection fraction on heart ultrasound examination in comparison with those treated without trimetazidine, so trimetazidin improve the metabolic balance of heart muscle.


Assuntos
Tolerância ao Exercício/efeitos dos fármacos , Coração/efeitos dos fármacos , Equivalente Metabólico/efeitos dos fármacos , Isquemia Miocárdica/tratamento farmacológico , Miocárdio/metabolismo , Qualidade de Vida , Trimetazidina/uso terapêutico , Ecocardiografia , Teste de Esforço , Tolerância ao Exercício/fisiologia , Feminino , Coração/fisiopatologia , Humanos , Masculino , Isquemia Miocárdica/metabolismo , Isquemia Miocárdica/fisiopatologia , Alta do Paciente , Esforço Físico , Volume Sistólico , Ultrassonografia , Vasodilatadores/uso terapêutico
20.
Georgian Med News ; (278): 87-93, 2018 May.
Artigo em Russo | MEDLINE | ID: mdl-29905551

RESUMO

This review is devoted to the urgent problem of cardiology and oncology - the cardiotoxicity of chemotherapy drugs - anthracyclines, which are considered to be one of the most cardiotoxic and cause a variety of cardiotoxic effects. The review also examines the diagnosis, treatment or preventive treatment of this pathology. The urgency of the problem is associated with the possibility of early or late manifestations of cardiotoxicity, manifestations of cardiotoxicity against the background of cross treatment, manifestations of cardiotoxicity against the background of various concomitant diseases. The review identified 9 main categories of cardiovascular complications during chemotherapeutic treatment and presents the types of cardiotoxicity caused by the use of anthracyclines. The issue of heart failure as a manifestation of anthracycline cardiotoxicity and the approaches to early diagnosis of cardiac insufficiency were examined in detail. The recommendations of the European Society of Medical Oncology (ESMO) (2012), the recommendations the European Society of Cardiology (ESC) in 2016 regarding the diagnosis and treatment of these patients are reviewed. An overview of the literature on the treatment and diagnosis of this category of patients is presented, especially with concomitant diseases. Examination of the patients, the timing of the initiation of therapy, preventive treatment, medication correction of heart failure, the doses, the combinations of chemotherapeutic drugs are issues that are recommended for the multidisciplinary team to successfully manage these patients.


Assuntos
Antraciclinas/efeitos adversos , Antineoplásicos/efeitos adversos , Cardiomiopatias/tratamento farmacológico , Cardiotônicos/uso terapêutico , Cardiotoxicidade/tratamento farmacológico , Insuficiência Cardíaca/prevenção & controle , Biomarcadores/sangue , Cardiomiopatias/sangue , Cardiomiopatias/induzido quimicamente , Cardiomiopatias/diagnóstico , Cardiotoxicidade/sangue , Cardiotoxicidade/diagnóstico , Cardiotoxicidade/etiologia , Ecocardiografia , Venenos Elapídicos/sangue , Coração/efeitos dos fármacos , Coração/fisiopatologia , Insuficiência Cardíaca/sangue , Insuficiência Cardíaca/induzido quimicamente , Insuficiência Cardíaca/diagnóstico , Humanos , Ivabradina/uso terapêutico , Peptídeo Natriurético Tipo C/sangue , Neoplasias/sangue , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Análise de Sobrevida , Trastuzumab/efeitos adversos , Trimetazidina/uso terapêutico , Troponina I/sangue
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