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Clinical effect of trimetazidine on prevention of contrast-induced nephropathy in patients with renal insufficiency: An updated systematic review and meta-analysis.
Ye, Z, Lu, H, Su, Q, Guo, W, Dai, W, Li, H, Yang, H, Li, L
Medicine. 2017;(9):e6059
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Abstract
BACKGROUND With the continuous development of cardiac interventional medicine, the incidence of contrast-induced nephropathy (CIN) is increasing every year, which is a serious threat to people's physical and mental health. Trimetazidine (TMZ) is a type of anti-ischemic drug developed in recent years, which can significantly reduce the incidence of CIN. At present, a systematic review and meta-analysis was conducted to evaluate the clinical effect of TMZ on prevention of CIN in patients with renal insufficiency. However, the study did not include patients from other countries and speaking different languages. So we conducted this study to update the previous meta-analysis that investigated the effects of TMZ on prevention of CIN in patients with renal insufficiency, and provided some theoretical reference for clinical. METHODS By searching PubMed, Embase, the Cochrane Library, Web of Science, CBM, CNKI, VIP database, and Wang Fang database for randomized controlled trial, which is comparing TMZ versus conventional hydration for prevention of CIN. Two researchers independently screened literature, and then evaluated the quality of literature and extracted the relevant data. Stata 11.0 software was used for statistical analysis. RESULTS Finally, this updated review showed that 3 studies that were not included in the previous meta-analysis were included in our study (3 articles were published in the Chinese Journal, 1 study for CIN, 1 study for CIN, serum creatinine (Scr), and superoxide dismutase, 1 study for CIN and Scr), and 1 outcome (Scr) reflecting the change of renal function was additionally included in our study. Of the 932 studies, 6 randomized controlled trials met the criteria, including 377 patients in TMZ group and 387 patients in control group. This meta-analysis for all studies showed that TMZ can significantly reduce the incidence of CIN (relative risk 0.27, 95% confidence interval [CI] 0.16, 0.46, P = 0.000), and can decrease the level of Scr after operation, including Scr of postoperative 24 hours (standardized mean difference [SMD] -0.30, 95% CI -0.51, -0.09, P = 0.005), Scr of postoperative 48 hours (SMD -0.66, 95% CI -1.23, -0.10, P = 0.022), and Scr of postoperative 7 days (SMD -0.74, 95% CI -1.36, -0.11, P = 0.021). However, the Scr of postoperative 72 hours between TMZ group and control group has no statistical significance (P = 0.362). CONCLUSION Our study showed that when comparing with conventional hydration, TMZ can significantly reduce the incidence of CIN and the level of postoperative Scr. Therefore, we could suggest that TMZ was superior to conventional hydration for the treatment of CIN in patients with renal insufficiency. However, due to the restriction of quality and number of included articles, it still needs to carry out multicenter, randomized, double-blind clinical trials to confirm this conclusion in the future.
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Trimetazidine in conditions other than coronary disease, old drug, new tricks?
Zou, H, Zhu, XX, Ding, YH, Jin, QY, Qian, LY, Huang, DS, Cen, XJ
International journal of cardiology. 2017;:1-6
Abstract
Trimetazidine (TMZ) has traditionally been used as an anti-ischemic drug for coronary artery disease by selectively inhibiting the mitochondrial long-chain 3-ketoacyl-CoA thiolase. Recently, new applications for this therapy have been investigated. This article reviews alternative uses for TMZ in non-coronary artery diseases, such as non-ischemic cardiomyopathy, sepsis, myocardial dysfunction induced by anti-cancer drugs, diabetic cardiomyopathy and contrast-induced nephropathy.
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Trimetazidine Decreases Risk of Contrast-Induced Nephropathy in Patients With Chronic Kidney Disease: A Meta-Analysis of Randomized Controlled Trials.
Nadkarni, GN, Konstantinidis, I, Patel, A, Yacoub, R, Kumbala, D, Patel, RA, Annapureddy, N, Pakanati, KC, Simoes, PK, Javed, F, et al
Journal of cardiovascular pharmacology and therapeutics. 2015;(6):539-46
Abstract
OBJECTIVES We sought to synthesize and analyze the available data from randomized controlled trials (RCTs) for trimetazidine (TMZ) in the prevention of contrast-induced nephropathy (CIN). BACKGROUND Contrast-induced nephropathy after coronary angiography is associated with poor outcomes. Trimetazidine is an anti-ischemic drug that might reduce incidence of CIN, but current data are inconclusive. METHODS We searched MEDLINE/PubMed, EMBASE, Scopus, Cochrane Library, Web of Science, and ScienceDirect electronic databases for RCTs comparing intravenous hydration with normal saline (NS) and/or N-acetyl cysteine (NAC) versus TMZ plus NS ± NAC for prevention of CIN. We used RevMan 5.2 for statistical analysis with the fixed effects model. RESULTS Of the 808 studies, 3 RCTs met criteria with 290 patients in the TMZ plus NS ± NAC group and 292 patients in the NS ± NAC group. The mean age of patients was 59.5 years, and baseline serum creatinine ranged from 1.3 to 2 mg/dL. Trimetazidine significantly reduced the incidence of CIN by 11% (risk difference 0.11; 95% confidence interval, 0.16-0.06; P < .01). There was no significant heterogeneity between the studies (I(2) statistic = 0). The number needed to treat to prevent 1 episode of CIN was 9. CONCLUSIONS The addition of TMZ to NS ± NAC significantly decreased the incidence of CIN in patients undergoing coronary angiography. In conclusion, TMZ could be considered as a potential tool for prevention of CIN in patients with renal dysfunction.
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The effectiveness of preoperative trimetazidine on myocardial preservation in coronary artery bypass graft patients: a systematic review and meta-analysis.
Zhang, N, Lei, J, Liu, Q, Huang, W, Xiao, H, Lei, H
Cardiology. 2015;(2):86-96
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Abstract
BACKGROUND Coronary artery bypass grafting (CABG) is a key and effective surgical treatment modality for coronary artery disease. Unfortunately, ischemia-reperfusion injury during and after CABG can lead to reversible and irreversible myocardial damage. Trimetazidine [1-(2,3,4-trimethoxybenzyl)piperazine dihydrochloride] is a metabolic anti-ischemic agent with demonstrated cardioprotective effects; however, its effects with respect to myocardial preservation in CABG patients remain unclear. METHODS We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) to investigate the effectiveness of myocardial preservation of preoperative trimetazidine therapy in CABG patients by assessing the postoperative levels of several blood-based biochemical markers of myocardial injury, including creatine kinase (CK), creatine kinase-muscle and brain (CK-MB), creatine phosphokinase (CPK), troponin T (TnT) and troponin I (TnI). The RCTs were classified into two subgroup analyses by the timing of sample collection (either ≤12 or >12 h after CABG). RESULTS Six RCTs were finally included in the meta-analysis. The pooled effect sizes showed significantly lower postoperative levels of CK, CK-MB, TnT and TnI in the trimetazidine-treated CABG patients relative to control CABG patients. However, there were no significant differences in the postoperative CPK levels between trimetazidine-treated CABG patients relative to control CABG patients. In both the ≤12 and >12 h post-CABG subgroup analyses, significant differences in CK, CK-MB, TnT and TnI were detected between the trimetazidine-treated CABG patients relative to control CABG patients. CONCLUSIONS Preoperative trimetazidine therapy appears to have a positive effect on myocardial preservation in CABG patients.
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Effects of metabolic approach in diabetic patients with coronary artery disease.
Fragasso, G, Salerno, A, Spoladore, R, Cera, M, Montanaro, C, Margonato, A
Current pharmaceutical design. 2009;(8):857-62
Abstract
The pivotal therapeutic role of myocardial metabolic modulation in ischemic heart disease (IHD) is increasingly recognized. Among the others, inhibitors of free fatty acids (FFA) oxidation have been consistently shown to play an important role in the therapeutic strategy of IHD patients. Additionally, abnormalities of glucose homeostasis are consistently present in patients with IHD, definitely contributing to the progression of the primary disease. If not adequately treated, in most patients glucose metabolism abnormalities will heavily contribute to the occurrence of complications, of whom severe left ventricular dysfunction is at present one of the most frequent and insidious. Apart from a meticulous metabolic control of frank diabetes, special attention should be also paid to insulin resistance, a condition that is generally underdiagnosed as a distinct clinical entity. An important metabolic alteration in diabetic patients is the increase in free fatty acid concentrations and the increased muscular and myocardial free fatty acid uptake and oxidation. The increased uptake and utilization of free fatty acid and the reduced utilization of glucose as source of energy during stress and ischemia are responsible for the increased susceptibility of the diabetic heart to myocardial ischemia and to a greater decrease of myocardial performance for a given amount of ischemia compared to non diabetic hearts. In order to shift cardiac metabolism from FFA to preferential glucose utilization, the use of FFA inhibitors has been advocated. Among FFA inhibitors etomoxir, perhexiline, oxfenicine and trimetazidine have been evaluated. Among them, trimetazidine, specifically a 3-ketoacyl coenzyme A thiolase inhibitor, has been shown to improve overall glucose metabolism in IHD patients with diabetes and left ventricular dysfunction. The observed combined beneficial effects of FFA inhibitors on myocardial ischemia, left ventricular function and glucose metabolism, represent an additional advantage of these drugs, especially when myocardial and glucose metabolism abnormalities coexist. In this paper, the recent literature on the beneficial therapeutic effects of FFA oxidation inhibitors on myocardial ischemia, left ventricular dysfunction and glucose metabolism in patients with ischemic heart disease and abnormalities of carbohydrate metabolism is reviewed and discussed.
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[Ischemic heart disease and left ventricular dysfunction: the role of trimetazidine].
Belardinelli, R
Italian heart journal : official journal of the Italian Federation of Cardiology. 2004;:23S-28S
Abstract
In patients with ischemic heart disease, contractility of dysfunctional myocardium may improve through metabolic modulation. Trimetazidine is the first of a new class of cytoprotective agents with antianginal properties. There is recent evidence that trimetazidine reduces fatty acid beta-oxidation and stimulates glucose oxidation by selective inhibition of 3-ketoacyl coenzyme A thiolase. In experimentally-induced myocardial ischemia, trimetazidine increases glucose oxidation by 210%, and this effect is associated with a 37% increase of pyruvate dehydrogenase. The increased rate of glucose oxidation reduces hydrogen ions and lactate accumulation, translating into improved myocardial contractility. In a recent randomized longitudinal placebo-controlled study in humans with ischemic cardiomyopathy, trimetazidine improved the contractile response of dysfunctional myocardium at doses of 20 mg tid for 8 weeks. This effect was associated with enhanced functional capacity and a higher ischemic threshold. The lack of effects on heart rate and blood pressure offers potential advantage in conditions of bradycardia and arterial hypotension. These important benefits need to be confirmed in larger longitudinal trials.
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[Trimetazidine and cardioprotection during ischemia-reperfusion].
Barsotti, A, Di Napoli, P
Italian heart journal : official journal of the Italian Federation of Cardiology. 2004;:29S-36S
Abstract
Although early reperfusion of ischemic myocardium is now considered to be the only intervention able to restore the various cellular functions altered by ischemia and to prevent progression toward cell death of myocardial cells due to necrosis or apoptosis, reperfusion is accompanied by various manifestations grouped under the heading of reperfusion damage or reperfusion syndrome. Functional recovery is therefore not immediate, but usually appears after a certain delay following a period of contractile dysfunction (myocardial stunning) lasting for several hours or even days after the start of reperfusion. The cellular mechanisms underlying the reperfusion damage may involve cellular calcium overload, over-production of oxygen-derived free radicals, cellular acidosis, inflammatory reaction, and microcirculatory dysfunction. Numerous pharmacological studies have been conducted to limit such reperfusion injury and, consequently, prevent stunning and/or reperfusion-induced arrhythmias. A number of experimental and clinical studies have demonstrated the beneficial effects of trimetazidine, a drug that inhibits the long-chain mitochondrial 3-ketoacyl coenzyme A thiolase enzyme in the myocyte, resulting in a shift from fatty acid oxidation to glucose oxidation. This optimization of cardiac metabolism results in direct anti-ischemic effects, limiting calcium accumulation and acidosis, inflammation and oxygen free radical production, and improvement of coronary microcirculation following reperfusion. This agent appears to be particularly promising clinically in the treatment of reperfusion injury, for example in combination with reperfusion strategies during the acute phase of myocardial ischemia or infarction, or in the reduction of the pro-remodeling effects of ischemia in patients with chronic ischemic syndrome and left ventricular dysfunction.
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Anti-ischaemic efficacy and tolerability of trimetazidine administered to patients with angina pectoris: results of three studies.
Szwed, H, Hradec, J, Préda, I
Coronary artery disease. 2001;:S25-8
Abstract
Several clinical studies have compared the anti-ischaemic properties of trimetazidine used as monotherapy with those of standard anti-anginal therapy. In the treatment of uncontrolled angina pectoris, the addition of a metabolic agent such as trimetazidine to existing therapy with a haemodynamic agent would appear to confer advantages over the addition of a second haemodynamic agent. Here we report the results of three studies conducted in Poland, the Czech Republic and Hungary that provide additional evidence for the beneficial effects of combining trimetazidine with a conventional haemodynamic agent such as beta-blockers, long-acting nitrate or calcium channel blockers. This combination provided significant benefits in terms of improved exercise capacity and decreased number of angina attacks along with a good tolerability profile.
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Trimetazidine and the contractile response of dysfunctional myocardium in ischaemic cardiomyopathy.
Belardinelli, R
Revista portuguesa de cardiologia : orgao oficial da Sociedade Portuguesa de Cardiologia = Portuguese journal of cardiology : an official journal of the Portuguese Society of Cardiology. 2000;:V35-9
Abstract
The therapeutic effect of anti-ischemic compounds is related to their ability to improve the oxygen supply-demand balance of the ischemic myocardium by increasing myocardial blood flow (calcium-antagonists), by reducing regional myocardial oxygen consumption (verapamil, betablockers) and increasing peripheral pooling of blood (nitrates, nifedipine). All these actions are also accompanied by hemodynamic changes, as evidenced by a lower double product, reduced wall stress, lower pulmonary wedge pressure, and lower systemic arterial pressure. In general, it was found that the combination of a betablocker with nifedipine improved the antianginal effect by further reducing the number and duration of ischemic events. The combination of a nitrate with a beta-blocker is particularly useful because it reduces the risk of heart failure by lowering left ventricular end-diastolic pressure and volume and by attenuating the negative inotropic effect of the betablocker. Although a combination therapy demonstrated benefits in comparison with drug treatment alone, it is associated with a higher incidence of untoward events. Trimetazidine (2, 3, 4 trimethoxybenzyl-piperazine dihydrochloride) is a novel anti-ischemic compound with a peculiar mechanism of action. Its anti-ischemic properties are unrelated to changes in myocardial oxygen supply-to-demand ratio, as shown by no significant effects on heart rate, blood pressure or rate-pressure product both at rest and during dynamic exercise. There are several possible mechanisms of action by which trimetazidine promotes preservation of membrane structures and cellular function: limitation of intracellular acidosis, correction of disturbances of transmembrane ion exchange leading to calcium overload, prevention of an excessive production of free radicals, inhibition of the inflammatory reaction and an antiplatelet effect. These documented actions cooperate to increase the rate of resynthesis of high-energy phosphates within myocardial cells after episodes of ischemia. In several trials, trimetazidine has been tested as an antianginal agent, both as monotherapy and combined with "classical" anti-ischemic compounds. In comparison with nifedipine, trimetazidine had similar efficacy in reducing the number of weekly anginal attacks and in increasing the ischemic threshold in a group of 39 patients with stable angina. However, the incidence of side effects was significantly higher with nifedipine (5 vs 20), and affected 5 patients with trimetazidine and 13 patients with nifedipine (p = 0.03). In a relatively large European study involving 149 patients (Trimetazidine European Multicenter Study, TEMS), trimetazidine (20 mg t.i.d.) was compared with propranolol (40 mg t.i.d.) in patients with stable angina pectoris and documented significant coronary artery stenoses. The number of anginal attacks was reduced equally by both drugs and exercise duration was increased by both treatments. However, in contrast with propranolol trimetazidine did not alter the rate pressure product. In patients already treated with nifedipine or beta-blockers, the addition of trimetazidine (20 mg t.i.d.) was able to reduce the number and the duration of anginal attacks and improved also the exercise capacity. Trimetazidine is generally well tolerated and only minor side effects have been reported (drowsiness, sedation, diarrhea). The improvement in cardiac energy metabolism should theoretically translate into enhancement in mechanical efficiency. This hypothesis has been object of recent investigations in patients with ischemic heart disease with and without left ventricular dysfunction. Brottier, et al. demonstrated that patients with ischemic cardiomyopathy treated with trimetazidine had a higher ejection fraction (measured by radionuclide angiography) than control patients who received a placebo after 6 months of therapy (p < 0.018). The group of Chierchia demonstrated that trimetazidine improved ischemic regional myocardial dysfunction at rest and during stress-induced ischemia in 15 patients with chronic coronary artery disease without affecting the hemodynamic determinants of myocardial oxygen consumption. There is recent demonstration that trimetazidine improves the contractile response of left ventricular hibernating myocardium in patients with ischemic heart disease. Belardinelli et al. showed that trimetazidine improved the contractile response of dysfunctional myocardial to low-dose dobutamine in patients with ischemic heart disease and left ventricular function. Twenty-two patients with prior anterior myocardial infarction and injection fraction < 35% (33 +/- 7%) were randomized into 2 groups. A group (= 11) received trimetazidine (20 mg tid) for 2 months, while another group (= 11) received a placebo. The usual medications were not altered during the study. (ABSTRACT TRUNCATED)