Objective To explore whether trimetazidine could improve symptoms, cardiac functions and clinical outcomes in patients with heart failure (HF). Methods A systematic literature search was conducted to identify randomised controlled trials (RCT) of trimetazidine for HF between 1966 and May 2010 in Pubmed, the Cochrane Central Registry of Clinical Trials and EMBASE. Reports of trials were sought that compared trimetazidine with placebo control for chronic HF in adults, with outcomes including all-cause mortality, hospitalisation, cardiovascular events, changes in cardiac function parameters and exercise capacity. Results 17 trials with data for 955 patients were identified by the literature search. Trimetazidine therapy was associated with a significant improvement in left ventricular ejection fraction in patients with both ischaemic (weighted mean difference (WMD) with placebo 7.37%; 95% CI 6.05 to 8.70; p<0.01) and non-ischaemic HF (WMD 8.72%; 95% CI 5.51 to 11.92; p<0.01). With trimetazidine therapy, left ventricular end-systolic volume was significantly reduced (WMD 10.37 ml; 95% CI 15.46 to 5.29; p<0.01) and New York Heart Association classification was improved (WMD 0.41; 95% CI 0.51 to 0.31; p<0.01) as was exercise duration (WMD, 30.26 s; 95% CI 8.77 to 51.75; p<0.01). More importantly, trimetazidine had a significant protective effect for all-cause mortality (RR 0.29; 95% CI 0.17 to 0.49; p<0.00001) and cardiovascular events and hospitalisation (RR 0.42; 95% CI 0.30 to 0.58; p<0.00001). Conclusion Trimetazidine might be an effective strategy for treating HF. More studies, especially larger multicentre RCT, are warranted to clarify the effect of trimetazidine on HF.With more than 5 million prevalent cases and nearly 1 million hospital discharges yearly, heart failure (HF) represents a rapidly growing therapeutic challenge for healthcare providers.

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Aliskiren is as effective as ARBs (losartan, valsartan, and irbesartan) in controlling BP and does not differ from ARBs in risk of adverse events.

Krüppel-like factor (KLF) 5, which initiates vascular smooth muscle cell (VSMC) proliferation, also participates in Angiotensin (Ang) II-induced vascular remodeling. The protective effect of rosiglitazone on vascular remodeling may be due to their impact on VSMC proliferation. However, the underlying mechanisms involved remain unclear. This study was designed to investigate whether the antiproliferation effects of rosiglitazone are mediated by regulating Ang II/KLF5 response. We found that, in aortas of Ang II-infused rats, vascular remodeling and KLF5 expression were markedly increased, and its target gene cyclin D1 was overexpressed. Co-treatment with rosiglitazone diminished these changes. In growth-arrested VSMCs, PPAR-γ agonists (rosiglitazone and 15d-PGJ2) dose-dependently inhibited Ang II-induced cell proliferation and expression of KLF5 and cyclin D1. Moreover, these effects were attenuated by the PPAR-γ antagonists GW9662, bisphenol A diglycidyl ether and PPAR-γ specific siRNA. Furthermore, rosiglitazone inhibited Ang II-induced phosphorylation of protein kinase C (PKC) ζ and extracellular signal-regulated kinase (ERK) 1/2 and activation of early growth response protein (Egr). In conclusion, in Ang II-stimulated VSMCs, rosiglitazone might have an antiproliferative effect through mechanisms that include reducing KLF5 expression, and a crosstalk between PPAR-γ and PKCζ/ERK1/2/Egr may be involved in. These findings not only provide a previously unrecognized mechanism by which PPAR-γ agonists inhibit VSMC proliferation, but also document a novel evidence for the beneficial vascular effect of PPAR-γ activation.

Angiotensin (Ang) II plays a critical role in cardiovascular remodeling. Krüppel-like factor (KLF) 5 is a novel indicated mediator in Ang II-induced cardiovascular damage. However, the potential link between KLF5 and Ang II has not been well investigated. In this study, we showed that in growth-arrested vascular smooth muscle cells (VSMCs), Ang II induced cell proliferation, KLF5 mRNA and protein expression in a dose-and time-dependent fashion, whereas KLF5 mRNA stability was not affected. The AT 1 antagonist losartan significantly blocked Ang II-induced KLF5 expression. Furthermore, several intracellular signals elicited by Ang II were involved in KLF5 gene upregulation, including phosphate tyrosine kinase, mitogen-activated protein kinases and reactive oxygen species. These data, for the first time, revealed the involvements of some intracellular signals in the regulation of KLF5 expression in response to Ang II in VSMCs and showed the possible role of KLF5 in Ang II-induced cell proliferation in VSMCs.