Efficacy And Safety Of Trimetazidine In Patients With Acute Coronary Syndrome:A Meta-Analysis Of 14 Randomized Controlled Trials

BackgroundPatients with acute coronary syndrome (ACS) are still experiencing remarkably higher rates of cardiovascular events, aggravated cardiac function, disappointing pessimistic prognosis and threaten of life. Trimetazidine (TMZ), an inhibitor of mitochondrial long-chain 3-ketoacyl coenzyme A thiolase, is confirmed to bring an increase of glucose oxidation by a shift of energy substrate from fatty acid to glucose oxidation. TMZ also has a myocytoprotective property against the ischemic damage to mitochondrial function, which seems not to induce changes in myocardial oxygen supply-to-demand ratio, hemodynamic conditions or in coronary blood flow at position emission tomography evaluation. However, the utility of trimetazidine in acute ischemia is controversial.AimsWe conducted this meta-analysis to determine the efficiency and safety of trimetazidine on outcomes and cardiac function parameters in patients with ACS.Data sourcesWe performed a systematic literature search for relevant randomized controlled trials (RCTs) published between 1980 and July 2015 in the Cochrane Library, Pubmed, and EMBASE. A manual search of reference lists was simultaneously performed.Data extractionTwo investigators extracted data and assessed the quality independently. The primary outcomes and cardiac function parameters:all-cause mortality, angina recurrence, ventricular fibrillation, ventricular tachycardia, atrioventricular block, reperfusion arrythmia, target vessel revascularization, reinfarction, new-onset heart failure (HF), left ventricular ejection fracture (LVEF), frequency of angina attack, resolution of ST segment deviation, serum CKMB, serum cTnl.Methods and ResultsFourteen trials with data for 21293 patients were included in our meta-analysis. We used a fixed-effects model or a random-effects model if necessary to calculate overall estimates, along with a funnel plot examined possibility of publication bias. Compared with placebo, TMZ treatment had no benefit on mortality (OR [odds ratio] 0.95; 95% CI [confidence interval],0.87 to 1.04; p=0.26) but can significantly improve LVEF, (WMD [weighted mean difference]-3.72%; 95% CI-4.74% to-2.70%; p<0.01), meanwhile remarkably ameliorate anginal pain and reduce the risk of new on-set HF as well as reperfusion arrythmia at the expense of increasing ventricular tachycardia (VT) during thrombolysis (OR 1.17; 95% CI 1.01 to 1.36; p=0.03).ConclusionShort-term TMZ supplementation (up to 3 months) have no protective effect against all-cause mortality and some of the major adverse events or lowering post-reperfusion serum CK-MB or cTnl level in ACS patients compared to placebo/ usual therapy. However TMZ effectively reduced the risk of recidivistic angina attack, reperfusion arrythmia, improve the left ventricular function and ameliorated weekly anginal pain at the expense of increasing ventricular tachycardia.Despite its limitations, our meta-analysis also bears the potential for TMZ on presentation with existing therapy, which may lead to better guidance of ACS treatment strategies and future prospective studies on this topic. Large-scale multi-central RCTs with longer follow-up are called for further elucidation of best regimen of TMZ supplementation in the future.BackgroundAntihypertensive agents may, even within the same class, exert variable effects on arterial stiffness variables. Selective β1-blockers could have a better impact than atenolol on arterial stiffness, by increasing the bioavailability of endothelium-derived nitric oxide.ObjectTo investigate the effect of selective β1-blocker On arterial stiffness and blood vessel function in mild to moderate essential hypertensionMethodWe investigated 2 beta-blockers (bisoprolol and nebivolol) on arterial stiffness variables. Treatment on patients (n 35; 62.9% males; age 54.5±9.28 years) with uncomplicated stage I-II essential hypertension were assigned to bisoprolol, or nebivolol for 12 weeks.ResultCentral systolic and diastolic blood pressure (BP), ABI, Ds, Dd, AC, VD, PWV(p=0.03, p=0.02) were measured at baseline and 12 weeks. Peripheral and central systolic and diastolic BP (p<0.01), AC (p=0.033), Ds, Dd (p<0.01) and PWV (baPWV p=0.03, haPWV p=0.02) were significantly and similarly reduced by those two β blocker agents. However, ABI (p=0.30), VD, Ep and β(p=0.056, p=0.297) continued to decline but no significant change was observed.ConclusionIn addition to reduction to blood pressure, selective β1-blocker plays an significant role in improving artery elasticity (PWV), and have the trend of improving vascular structures to some extent. Moreover, large scaled randomized controlled clinical trials are called for further proof, and the clinical relevance of molecular biology parameters and artery stiffness still remains to be established.