[SD-FORUM-LAT] 40E RE: Trimetazidina. Dr. Perez Riera

SCD Symposium info en scd-symposium.org
Lun Oct 16 23:47:48 ART 2006


Español - Portugués

Español

Estimado Dr. Salim Ben Khedda, de la División de Cardiología del  
Hospital Mustapha, Centro Médico de Algeria:
Soy Andrés Ricardo Pérez Riera de San Pablo, Brasil.
Hay varios trabajos randomizados, principalmente de Italia (Clinical  
Cardiology-Heart Failure Unit, Istituto Scientifico-Universita Vita/ 
Salute San Raffaele, Milan) pero no directamente relacionados con la  
mortalidad.
Por favor, vean más adelante:
Principales referencias indexadas sobre Trimetazidina con metodología  
de doble ciego y randomización.

Cordialmente,
Andrés Ricardo Pérez Riera
Chief of Electro-Vectocardiology Sector of the Discipline of  
Cardiology,ABC Faculty of Medicine (FMABC), Foundation of ABC  
(FUABC)- Santo André -São Paulo - Brazil. Rua Sebastião Afonso  885 -  
Zip Code: 044417-100- Jardim Miriam  S.P.- Brazil

--------

Portugués

Caro Dr Salim Ben  Khedda da Divisão de Cardiologia do Mustapha  
Hospital Centro médico Algeirs Algeria: aqui é Andrés Ricardo Pérez  
Riera de Sao Paulo Brasil.
Eles são vários artigos andomizados, principalmente da Itália  
(Clinical Cardiology-Heart Failure Unit, Istituto Scientifico- 
Universita Vita/Salute San Raffaele,Milan ) mas não relacionados  
diretamente a mortalidade.
Por favor veja abaixo.
Principais referências indexadas com metodologia duplo-cego randomizada.

Tudo de Bom
Andrés Ricardo Pérez Riera
Chefe do Setor de Eletrovetocardiografia da Disciplina de  
Cardiologia, Faculdade de Medicna do ABC (FMABC), Fundação do ABC  
(FUABC)- Santo André -São Paulo - Brasil. Rua Sebastião Afonso  885 -  
CEP: 044417-100- Jardim Miriam  S.P.- Brasil


Referencias - Referências

Fragasso G, Palloshi A, Puccetti P, et al. A randomized clinical  
trial of trimetazidine, a partial free fatty acid oxidation  
inhibitor, in patients with heart failure. J Am Coll Cardiol. 2006;48 
(5):992-8.
Clinical Cardiology-Heart Failure Unit, Istituto Scientifico- 
Universita Vita/Salute San Raffaele, Milan, Italy.  
gabriele.fragasso en hsr.it
OBJECTIVES: This study sought to assess whether the long-term  
addition of trimetazidine to conventional treatment could improve  
functional class, exercise tolerance, and left ventricular function  
in patients with heart failure (HF). BACKGROUND: Previous small  
studies have shown that trimetazidine may be beneficial in terms of  
left ventricular function preservation and control of symptoms in  
patients with post-ischemic HF. METHODS: Fifty-five patients with HF  
were randomly allocated in an open-label fashion to either  
conventional therapy plus trimetazidine (20 mg three times daily) (28  
patients) or conventional therapy alone (27 patients). Mean follow-up  
was 13 +/- 3 months. At study entry and at follow-up, all patients  
underwent exercise testing and two-dimensional echocardiography.  
Among the others, New York Heart Association (NYHA) functional class  
and ejection fraction (EF) were evaluated. RESULTS: In the  
trimetazidine group, NYHA functional class significantly improved  
compared with the conventional therapy group (p < 0.0001). Treatment  
with trimetazidine significantly decreased left ventricular end- 
systolic volume (from 98 +/- 36 ml to 81 +/- 27 ml, p = 0.04) and  
increased EF from 36 +/- 7% to 43 +/- 10% (p = 0.002). On the  
contrary, in the conventional therapy group, both left ventricular  
end-diastolic and -systolic volumes increased from 142 +/- 43 ml to  
156 +/- 63 ml, p = 0.2, and from 86 +/- 34 ml to 104 +/- 52 ml, p =  
0.1, respectively; accordingly, EF significantly decreased from 38  
+/- 7% to 34 +/- 7% (p = 0.02). CONCLUSIONS: In conclusion, long-term  
trimetazidine improves functional class and left ventricular function  
in patients with HF. This benefit contrasts with the natural history  
of the disease, as shown by the decrease of EF in patients on  
standard HF therapy alone.
PMID: 16949492 [PubMed - indexed for MEDLINE]

Fragasso G, Montano C, Perseghin G, Palloshi A, et al. The anti- 
ischemic effect of trimetazidine in patients with postprandial  
myocardial ischemia is unrelated to meal composition. Am Heart J.  
2006;151:1238.e1-8.
Heart Failure Unit, Clinical Cardiology, Istituto Scientifico/ 
Universita' San Raffaele, Milan, Italy. gabriele.fragasso en hsr.it
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.
PMID: 16781225 [PubMed - indexed for MEDLINE]

Fragasso G, Perseghin G, De Cobelli F, et al.Effects of metabolic  
modulation by trimetazidine on left ventricular function and  
phosphocreatine/adenosine triphosphate ratio in patients with heart  
failure. Eur Heart J. 2006;27:942-948.
Department of Clinical Cardiology, Heart Failure Clinic, Istituto  
Scientifico/Universita' San Raffaele, Via Olgettina 60, 20132 Milano,  
Italy. gabriele.fragasso en hsr.it
AIMS: The addition of trimetazidine to standard treatment has been  
shown to improve left ventricular (LV) function in patients with  
heart failure. The aim of this study is to non-invasively assess, by  
means of in vivo 31P-magnetic resonance spectroscopy (31P-MRS), the  
effects of trimetazidine on LV cardiac phosphocreatine and adenosine  
triphosphate (PCr/ATP) ratio in patients with heart failure. METHODS  
AND RESULTS: Twelve heart failure patients were randomized in a  
double-blind, cross-over study to placebo or trimetazidine (20 mg  
t.i.d.) for two periods of 90 days. At the end of each period, all  
patients underwent exercise testing, 2D echocardiography, and MRS.  
New York Heart Association (NYHA) class, ejection fraction (EF),  
maximal rate-pressure product, and metabolic equivalent system (METS)  
were evaluated. Relative concentrations of PCr and ATP were  
determined by cardiac 31P-MRS. On trimetazidine, NYHA class decreased  
from 3.04+/-0.26 to 2.45+/-0.52 (P = 0.005), whereas EF (34+/-10 vs.  
39+/-10%, P = 0.03) and METS (from 7.44+/-1.84 to 8.78+/-2.72, P =  
0.03) increased. The mean cardiac PCr/ATP ratio was 1.35+/-0.33 with  
placebo, but was increased by 33% to 1.80+/-0.50 (P = 0.03) with  
trimetazidine. CONCLUSION: Trimetazidine improves functional class  
and LV function in patients with heart failure. These effects are  
associated to the observed trimetazidine-induced increase in the PCr/ 
ATP ratio, indicating preservation of the myocardial high-energy  
phosphate levels.
PMID: 16510466 [PubMed - indexed for MEDLINE

Iskesen I, Saribulbul O, Cerrahoglu M,et al. Trimetazidine reduces  
oxidative stress in cardiac surgery. Circ J. 2006 Sep;70(9):1169-73.  
Department of Cardiovascular Surgery, Celal Bayar University School  
of Medicine, Turkey. iskesen en yahoo.com
BACKGROUND: Trimetazidine is an anti-ischemic agent that is used to  
treat angina and it has cardioprotective effects without inducing any  
significant hemodynamic changes. It inhibits the long-chain  
mitochondrial 3-ketoacyl coenzyme A thiolase enzyme in the myocyte  
and can improve cardiac mitochondrial metabolism, as well as scavenge  
free radicals. The aim of this double-blind prospective randomized  
study was to investigate the effect of preoperative use of  
trimetazidine on the reduction of oxidative stress during coronary  
artery bypass grafting (CABG) under cardiopulmonary bypass (CPB).  
METHODS AND RESULTS: The study group (group T) and the control group  
(group C) each comprised 12 patients. Pretreatment began 2 weeks  
before CABG with trimetazidine (60 mg/day po); the control group did  
not receive any medication. Serial blood samples were collected  
before and after CPB for measurement of the serum concentrations of  
these major endogenous antioxidant enzyme systems, which are markers  
for oxidative degradation of the cellular membranes; postoperative  
levels were significantly different between the groups (p<0.05).  
There were no significant difference in hemodynamic values.  
CONCLUSION: The findings suggest that pretreatment with trimetazidine  
alleviates malondialdehyde production and preserves endogenous  
antioxidant capacity during CABG with CPB and cardioplegic arrest.
PMID: 16936431 [PubMed - indexed for MEDLINE]
Chaloupka V. Trimetazidine in the treatment of stable angina pectoris  
TRIADA-(trimetazidine in stable angina twice daily) Vnitr Lek. 2006  
Jun;52(6):609-14. [Article in Czech]
Interni kardiologicka klinika Lekarske fakulty MU a FN Brno.  
vchaloup en fnbrno.cz
              Links
Comment in:
Vnitr Lek. 2006 Jun;52(6):556-7.
Vnitr Lek. 2006 Jun;52(6):558-9.
The primary objective of the national study TRIADA was to evaluate  
the efficacy and tolerability of Preductal MR (trimetazidine) at a  
dose of 35 mg twice daily which was added to current therapy  
involving the maximum of two antianginal drugs. The outcome was  
evaluated after 12 weeks of therapy and compared with baseline data.  
The study included 74 patients with stable exertional angina pectoris  
(AP) and positive exercise testing results. Trimetazidine (Preductal  
MR) at a dose of 35 mg twice daily was added to their current therapy  
involving two drugs at most. TRIADA confirmed that the use of  
trimetazidine in a new pharmacological form is effective and well  
tolerated in the treatment of angina pectoris. The study also  
confirmed a beneficial effect of trimetazidine on the incidence of  
angina pectoris paroxysms and objective manifestations of ischaemia  
during exercise testing. Holter monitoring clearly showed that  
metabolic therapy added to standard antianginal therapy would reduce  
the incidence of symptomatic and asymptomatic ischaemia. In addition,  
12-week therapy with trimetazidine helped improve all end points of  
quality of life of AP patients evaluated using a questionnaire for AP  
patients (The Seattle Angina Questionnaire).
PMID: 16871765 [PubMed - indexed for MEDLINE]

Topal E, Ozdemir R, Barutcu I, et al. The effects of trimetazidine on  
heart rate variability in patients with slow coronary artery flow. J  
Electrocardiol. 2006 Apr;39(2):211-8.
Cardiology Department, Faculty of Medicine, Inonu University, Malatya  
34300, Turkey.
OBJECTIVE: We sought to examine the effect of trimetazidine (TMZ) on  
heart rate variability (HRV), endothelin-1 (ET-1), NO, and anginal  
symptoms in patients with slow coronary artery flow (SCAF). METHODS:  
The 48 patients with SCAF (29 women and 19 men; mean age, 52 +/- 9  
years) were included in the study. Twenty milligrams TMZ 3 times a  
day or matched placebo were given randomly in a double-blinded  
fashion for 4 weeks. Patients were divided into 4 groups as follows:  
exercise-positive, TMZ-given group (group A, n = 12); exercise- 
positive, placebo-given group (group B, n = 12); exercise-negative,  
TMZ-given group (group C, n = 12); and exercise-negative, placebo- 
given group (group D, n = 12). RESULTS: After TMZ treatment, HRV  
parameters, including SD of the all R-R intervals, SD of the averages  
of R-R intervals in all 5-minute segments of the entire recording,  
percentage of R-R intervals with more than 50-millisecond variation,  
and the square root of the mean of the sum of the squares of  
differences between adjacent R-R intervals, significantly improved  
both in exercise-positive and exercise-negative groups when compared  
with baseline. After TMZ treatment, ET-1 and NO levels significantly  
altered both in exercise-positive and exercise-negative groups when  
compared with baseline (17.7 +/- 2.7 vs 13.9 +/- 2.8 pg/mL [P = .01]  
and 18.1 +/- 3.8 vs 14.2 +/- 2.6 pg/mL [P = .01], respectively).  
After TMZ treatment, NO levels significantly increased in both  
exercise-positive and exercise-negative groups when compared with  
baseline (36.4 +/- 5.4 vs 43.3 +/- 6.8 micromol/L [P = .01] and 36.8  
+/- 7.8vs 43.3 +/- 4.8 micromol/L [P = .01], respectively). However,  
in placebo group, neither HRV parameters nor ET-1 and NO levels  
altered when compared with baseline. Also, after treatment, a  
significant correlation was detected between HRV parameters,  
including SD of the averages of R-R intervals in all 5-minute  
segments of the entire recording, SD of the all R-R intervals,  
percentage of R-R intervals with more than 50-millisecond variation,  
and the square root of the mean of the sum of the squares of  
differences between adjacent R-R intervals, and NO and ET-1 levels in  
TMZ group but not placebo. CONCLUSION: Short-term TMZ therapy  
improved HRV parameters and endothelial products such as ET-1 and NO  
as well as anginal symptom in patients with SCAF. Improvement in HRV  
parameters was correlated with ET-1 and NO levels.
             PMID: 16580422 [PubMed - indexed for MEDLINE]


--
Dr. Sergio Dubner
President of Scientific Committee

Dr. Edgardo Schapachnik
President of Steering Committee


> Español - Portugués
>
> Español
>
> Estimados colegas:
> Felicitaciones por este excelente evento.
> Quisiera preguntarle al Dr. Andrés Ricardo Pérez Riera, en términos  
> de medicina basada en evidencias, ¿hay algún ensayo que muestre una  
> mejora de la morbi-mortalidad al usar trimetazidina (TMZ) vartel?
> Muchas gracias por su consideración a este mensaje.
> salim BEN KHEDDA
> cardiology division
> Mustapha Hospital medical Center
> Algeirs Algeria
>
> ---------
>
> Portugués
>
> Caros colegas,
> Congratulações por este excelente encontro:
> Eu gostaria de pergunatr ao Dr Andrés Ricardo Pérez Riera. em  
> termos de ^medicina baseada em evidência existe algum estudo  
> demonstrando a morbi-mortalidade com o uso da Trimetazidina (TMZ)  
> Vastarel
> Muito obrigado por sua consideração com esta menssagem.
> salim BEN KHEDDA
> Disisão de Cardiologia
> Mustapha Hospital medical Center
> Algeirs Algeria
>
>
> --
> Dr. Sergio Dubner
> President of Scientific Committee
>
> Dr. Edgardo Schapachnik
> President of Steering Committee
>
>
>
>
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