Objective To systematically assess the effectiveness and safety of atorvastatin in patients with dilated cardiomyopathy (DCM) complicating chronic heart failure (CHF). Methods Databases including PubMed, The Cochrane Library, EMbase, CNKI, CBM, and VIP were searched from inception to November 2011 to collect randomized controlled trials (RCTs) on atorvastatin for DCM accompanied with CHF. According to the inclusion criterion, relevant articles were screened. Then we extracted data, assessed quality, and performed meta-analysis using RevMan 5.0. Results A total of 11 RCTs involving 648 patients were included. The result of meta-analyses showed that compared with the control group at the sixth month after treatment, in the atorvastatin group, left ventricular ejection fraction (LVEF) obviously (MD=3.92, 95%CI 1.93 to 5.92, P=0.000 1) and 6-minute walk distance (MD=13.15, 95%CI 5.47 to 20.83, P=0.000 8) increased. Besides, serum level of CRP obviously decreased in the atorvastatin group (MD=1.91, 95%CI 3.03 to 0.79, P=0.000 9). Conclusion Current evidence indicates that atorvastatin, based on routine treatment, can improve cardiac function to some extent, increase LVEF, and reduce serum levels of inflammatory markers for patients with DCM complicating CHF. Therefore, atorvastatin is likely to be a safe and effective drug for non-ischemic cardiomyopathy due to DCM, which still has to be proved by more large-scale and high-quality clinical trials.
ObjectivesTo systematically review the influence of nifedipine combined with atorvastatin on hypertension in patients with hypertension.MethodPubMed, EMbase, The Cochrane Library, CBM, CNKI, WanFang Data and VIP databases were electronically searched to collect randomized controlled trials (RCTs) of nifedipine combined with atorvastatin on hypertension in patients with hypertension from inception to November 20th, 2018. Two reviewers independently screened literature, extracted data and assessed the risk of bias of included studies, then, meta-analysis was performed by using Stata 12.0 software.ResultsA total of 17 RCTs involving 1 838 patients were included. The results of meta-analysis indicated that nifedipine combined with atorvastatin was superior to nifedipine alone on SBP (MD=−8.937, 95%CI−11.913 to −5.962, P<0.001), DBP (MD=−3.702, 95%CI−6.626 to −0.778, P=0.013) and total effective rate (RR=1.24, 95%CI 1.07 to 1.44, P=0.003). There was no significant difference between two groups in the incidence of adverse reactions (P>0.05).ConclusionsCurrent evidence shows that nifedipine combined with atorvastatin can significantly improve total effective rate, decrease the level of SBP and DBP, and increasing of dose not increase the incidence of adverse reactions. Due to limited quality and quantity of the included studies, more high quality studies are required to verify above conclusions.
Objective To systematically review the effectiveness and safety of Zhibitai vs. atorvastatin in the treatment of hyperlipidemia. Methods Randomized controlled trials (RCTs) about Zhibitai vs. atorvastatin for hyperlipidemia were electronically retrieved in databases of PubMed, CENTRAL (Issue 7, 2010), CBM,CNKI, VIP and WanFang Data from inception to July, 2012. Two reviewers independently screened literature, extracted data, and assessed methodological quality. Then, meta-analysis was conducted using RevMan 5.2 software. Results A total of 4 RCTs involving 519 cases were included. The results of meta-analysis showed, Zhibitai was superior to atorvastatin in reducing TG levels after 8-week treatment (MD= −0.12, 95%CI −0.23 to −0.01, P=0.03) and increasing HDL-C levels after 8-week treatment (MD= −0.16, 95%CI −0.22 to −0.11, P=0.000 01). But there was no significant difference in decreasing TC levels and LDL-C levels after 4-week treatment and 8-week treatment as well as decreasing TG levels after 4-week treatment between the two groups. No obvious adverse reaction occurred in the two groups, but atorvastatin may impair liver function. Conclusion Current evidence with weak strength shows that, Zhibitai is superior to atorvastatin in reducing TG levels, and increasing HDL-C levels after 8 weeks. However, they are alike in other blood-fat index and safety. Due to the limited quantity and quality of the included studies, more high quality RCTs are needed to verify the above conclusion.
目的：探讨阿托伐他汀治疗高脂血症患者的疗效分析。方法： 对70例确诊高脂血症的患者给予阿托伐他汀10 mg，每日一次，连服3个月，观察观察治疗前后的血脂、肝功能、肾功能,同时观察患者有无不良反应。结果：治疗3个月后,TC、TG、LDL-C均较治疗前显著下降(Plt;0.05),HDL-C较治疗前明显提高(Plt;0.05),TC、TG、LDL-C、HDL-C治疗3个月的总有效率分别是84.28%、74.6%、80%和62.26%,未见明显不良反应。结论：阿托伐他汀治疗高脂血症患者安全有效。
ObjectiveTo investigate the effects of migration and expression from chemokine receptor 4 (chemokine receptor-4, CXCR4) of rat bone marrow mesenchymal stem cells (BMSCs) which were pretreated by atorvastatin (ATV) in vitro.MethodsIsolated, cultivated, identified the BMSCs, pretreated P4-P6 of BMSCs with different concentrations of ATV for 12 hours. The experimental group was divided into control group, 0.1 nM/L (group 0.1 nM), 1 nM/L (1 nM group), 10 nM/L (10 nM group), 100 nM/L (100 nM group), 1 000 nM/L (1 000 nM group). The mRNA and protein of CXCR4 were determined by real time-polymerase chain reaction and Western blot. Immunofluoreseence assay were used to detect the expression levels of CXCR4. The migration ability of BMSCs were measured by transwell chamber.ResultsImmunofluoreseence assay showed the protein level of CXCR4 of group 1 nM and 10 nM were significantly higher than the other group. RT-PCR and Western blot showed the protein and mRNA level of CXCR4 in 10 nM was higher than that in group 1 nM. The migration ability of group 10 nM was higher than 1 nM and control group.ConclusionsATV can be dose-dependent promote expression levels of CXCR4 of BMSCs cultivated in vitro.
ObjectTo observe the clinical efficacy and safety of the combination therapy of atorvastatin and JiangZhi Decoction (ZJD) for primary hyperlipidemia (Tan Zhuo Zu E Zheng) and to analyze the interactions of drugs in hypolipidemic effect. MethodsA 2*2 factorial design, single-blind, stratified randomized controlled trial according to the level of lipid was conducted. Primary hyperlipidemia (Tan Zhuo Zu E Zheng) patients met the inclusion criteria were divided into 5 groups:ATV 10 mg group (group A), ATV 20 mg group (group B), ATV 10 mg+JZD group (group C), ATV 20 mg+JZD group (group D), JZD group (group E). After two weeks treatment, the efficacy and safety among the 5 groups were compared. ResultsA total of 92 patients were included, of which, 20 were in group A, 25 in group B, 21 in group C, 17 in group D, and 9 in group E. The results showed that:(1) There was no significant difference between group C and group B in the reduction of serum total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) (PTC=0.226, PLDL-C=0.818). (2) The results of 2*2 factorial analysis showed that, there was no significant interaction between TCM factor and western medicine factor (PTC=0.605, PLDL-C=0.843). (3) There were no significant differences in safety outcomes among 5 groups (all P values >0.05). ConclusionATV 10 mg+JZD and ATV 20 mg have a similar efficacy in reducing TC and LDL-C. There is no obvious interaction between JZD and ATV in hypolipidemic effect, and the combination therapy of ATV and JZD is safe.
ObjectiveTo investigate the effects and mechanism of atorvastatin in the experimental pulmonary fibrosis. MethodsFifty-four C57BL/6 mice were randomly divided into a control group,a bleomycin group and an atorvastatin group. The mice in the bleomycin group and the atorvastatin group received a single dose intratracheal injection of bleomycin (2.5 mg/kg),while the mice in the control group were injected with isodose physiological saline. The mice in the atorvastatin group were treated with atorvastatin 10 mg·kg-1·d-1 by intragastric administration the day after bleomycin instillation. All groups were sacrificed on the day 3,14 and 28,respectively. HE staining and Masson staining were used to detect the architecture of alveolar and the deposition of cellularity and collagen. RT-PCR and immunohistochemical technology were performed to detect the expression of Krüppel like factor 4 (KLF4). Zymography was used to investigate the activation of matrix metalloproteinase-2(MMP-2). ResultsAfter the treatment of bleomycin,the lung tissues showed acute inflammation on the day 3,the collagen deposition was more obvious and the architecture of alveolar was destroyed on the day 14. The alveolar structure,the inflammation and collagen deposition were attenuated on the day 28 compared with the day 14. Compared with the bleomycin group,the inflammation and the collagen deposition were significantly reduced in the atorvastatin group (P<0.05). Compared with bleomycin group,the expression of KLF4 significantly decreased in the atorvastatin group,although the expression of KLF4 mRNA increased on the day 3 compared with the bleomycin group (0.502±0.261 vs. 0.326±0.164,P<0.05). The expression of KLF4 protein on the day 3 was significantly decreased compared with the bleomycin group (0.048±0.015 vs. 0.130±0.017,P<0.05). After the intervention of bleomycin,the activation of MMP-2 on the day 3 and 14 significantly increased compared with the control group (3.136±1.321 and 3.449±0.356 vs. 0.983±0.147,P<0.05),and significantly decreased after the treatment of atorvastatin (2.191±0.800 and 2.506±0.761). ConclusionAtorvastatin may have anti-inflammation and anti-fibrosis activities in experimental pulmonary fibrosis through KLF4 pathway.
ObjectiveTo investigate whether exosomes derived from atorvastatin (ATV)-pretreated human umbilical cord mesenchymal stem cells (ATV-MSC-EXO) alleviate high glucose-induced injury in human retinal vascular endothelial cells (HREC) via the protein kinase B (AKT)/endothelial nitric oxide synthase (eNOS) signaling pathway. MethodsThe optimal pretreatment concentration of ATV was determined using the cell counting Kit-8 (CCK-8) assay. Exosomes derived from mesenchymal stem cells (MSC-EXO) and ATV-pretreated MSC (ATV-MSC-EXO) were isolated and extracted, and their morphology and surface markers were characterized by transmission electron microscopy, nanoparticle tracking analysis, and Western blotting (WB). The uptake capacity of exosomes by human retinal vascular endothelial cells (HREC) was evaluated using a fluorescence labeling assay. In vitro cultured HREC were divided into the following groups: normal control group (NC group), high glucose group (HG group), high glucose+MSC-EXO group (MSC-EXO group), high glucose+ATV-MSC-EXO group (ATV-MSC-EXO group), high glucose+ATV-MSC-EXO+AKT inhibitor group (ATV-MSC-EXO-MK-2206-2HCL group), and high glucose+ATV-MSC-EXO+eNOS inhibitor group (ATV-MSC-EXO-L-NAME group). Cell proliferation and apoptosis were detected using CCK-8 and flow cytometry, respectively. The protein expression levels of B-cell lymphoma/leukemia-2 (Bcl-2), Bcl-2-associated protein (Bax), and Caspase-3 were measured by WB. In addition, the regulatory effects of ATV-MSC-EXO on the AKT/eNOS signaling pathway and its downstream functional molecules were analyzed by detecting the phosphorylation levels of AKT (P-AKT/AKT) and eNOS (P-eNOS/eNOS) via WB, the mRNA expression levels of AKT and eNOS by quantitative real-time polymerase chain reaction, and the concentrations of nitric oxide (NO) and endothelin-1 (ET-1) using commercial NO and ET-1 assay kits. ResultsThe optimal pretreatment concentration of ATV was 1 μmol/L. ATV-MSC-EXO exhibited similar morphology and particle size to MSC-EXO and were efficiently taken up by HREC. Under high glucose conditions, ATV-MSC-EXO significantly enhanced the viability of HREC (F=83.24, P＜0.000 1) and inhibited apoptosis (F=77.39, P＜0.000 1). WB analysis further confirmed that ATV-MSC-EXO upregulated the expression of the anti-apoptotic protein Bcl-2 (F=53.17), while downregulating the pro-apoptotic proteins Bax (F=36.49) and Caspase-3 (F=60.75) (P＜0.001). In addition, ATV-MSC-EXO markedly increased the protein levels of P-AKT/AKT (F=107.60) and P-eNOS/eNOS (F=38.59), as well as the relative mRNA expression of AKT, eNOS (F=203.60, 315.00; P＜0.000 1). Furthermore, ATV-MSC-EXO promoted NO production (F=407.40) and suppressed the relative expression of ET-1 (F=49.76) (P＜0.000 1). ConclusionATV-MSC-EXO enhances the viability and inhibits apoptosis of HREC under high glucose conditions by activating the AKT/eNOS signaling pathway.
Objective To assess the effectiveness and safety of nine lipid-lowing agents in the national essential drug list (2000) and provide evidence for the adjustment and selection of essential drugs. Methods Based on principles of health technology assessment (HTA) and evidence-based medicine, we searched for all published clinical studies about these drugs from the following databases: MEDLINE (1966-2002.8), The Cochrane Library, EMBASE (1974-2002), CBMdisk (1979-2002.8) and VIP (1989-2002.8), the database of National Center for Adverse Drug Reaction(ADR) Monitoring of China and the database of WHO Uppsala drug monitoring center. Included studies were appraised, analyzed and compared for the reduction of triglyceride (TC) or low density lipoprotein (LDL-C), the prevention for the coronary events and the incidence of ADR. Results The results from comparative trials for lipid-lowing agents showed that the equivalent dose of statins for 25% reduction of LDL-C was atorvastatin 10 mg/d, simvastatin 20 mg/d, pravastatin 40mg/d, lovastatin 40 mg/d, cerivastatin 0.3 mg/d and fluvastatin 80 mg/d. It was difficult to compare fenofibrate with gemfibrozil, acipimox with statins or fibrates based on available data. The study on the primary and secondary prevention of cardiovascular events showed that pravastatin and lovastatin were effective in primary prevention, and long-term use could reduce the incidence of cardiovascular disease.Gemfibrozil could reduce the mortality from coronary heart disease (CHD) but the overall mortality was not changed. Pravastatin, simvastatin, atorvastatin, fluvastatin, gemfibrozil and fenofibrate had a confirmed effect in secondary prevention. Data from large-scale clinical trials and the reports from ADR monitoring center of England, America, Canada and Australia suggested that the statins which had rare ADR were safe and tolerated. Rhabdomyolysis was rare but had a serious adverse reaction associated with statins. The rate of fatal rhabdomyolysis related to cerivastatin was the highest among 6 statins. The safety of simvastatin, lovastatin and atorvastatin was lower than cerivastatin but higher than simvastatin and atorvastatin. The number of ADR reports of fenofibrate was fewer than that of gemfibrozil. Conclusions At present, the best evidence focused on pravastatin, simvastatin and lovastatin are widely used and have a confirmed safety and efficacy. Atorvastatin, fluvastatin and fenofibrate still need more data to confirm their effects on coronary heart disease prevention. The drugs which were shown to be inferior or insufficient evidence are cerivastatin, gemfibrozil and acipimox.