Objective To explore the effects of aggressive lipid lowering therapy and its influence on cardiovascular events using lipitor (20 mg daily) for Chinese people after percutaneous coronary intervention (PCI). Methods We did a double-blind and randomized controlled trial. From July 2005 to June 2006, 120 patients with PCI procedure who were discharged from the Shanghai Chest Hospital were randomly divided into aggressive lipid lowering group (atorvastatin 20 mg daily, n=60) and an ordinary lipid lowering group (atorvastatin 10 mg daily, n=60). The trial treatment was administered from the day of PCI to the third month after PCI. Atorvastatin at 10 mg daily was then used until one year after PCI. Blood biochemistry, cardiovascular events and drug adverse reactions were compared between the two groups. Results Among the 120 patients, 5 discontinued treatment and 4 more withdrew from the study. Therefore 115 and 111 were included in our main analyses [Comment from Mike: it is not ITT if the 5 who discontinued treatment are excluded] and a per-protocol (PP) analysis, respectively. Baseline clinical characteristics were comparable between the two groups. The reduction in TG and the increase in HDL-C were similar between the two groups (Pgt;0.05), but the reductions in LDL-C and TC were significantly different between the two groups (Plt;0.05). This was observed from the beginning of follow-up to the third month after PCI. In the PP analysis, the percentage of patients whose LDL-C met the predefined requirement at the third month in the 20 mg group was significantly higher than in the group receiving the lower dose (87.03% vs. 70.17%, P=0.031). A similar result was also obtained if the patients who withdrew were retained in the analysis (P=0.044). The change in C reaction protein (CRP) from baseline at the first and the third month was significantly different between the two groups (Plt;0.05), but become relatively stable at the sixth month (Pgt;0.05). The mean follow-up duration was 6.5±3.0 months in the higher dose group, with 1 case of recurring angina pectoris and 1 case of revascularization were identified. It was 7.2±3.6 months in the 10 mg daily group, with 3 cases of recurring angina pectoris, 1 case of nonfatal myocardial infarction, 2 cases of revascularization and 1 case of sudden cardiogenic death. The difference in the Kaplan-Meier event curves was of borderline statistical significance from the fourth month (P=0.048). Drug adverse reactions were mild and myopathy was not identified in any patients. Conclusions After PCI procedure, the use of atorvastatin 20 mg daily for aggressive lipid lowering was safe and effective.
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 observe and analyze the short-term efficacy of different statins on acute myocardial infarction in patients with premature coronary heart disease. MethodWe selected 70 patients with acute myocardial infarction admitted into our hospital for treatment of premature coronary artery disease between January 2012 and June 2013. The patients were randomly divided into experimental group (n=35) and control group (n=35). The experimental group were treated with rosuvastatin, and the control group of patients were given atorvastatin. We observed the rate of overall efficiency within 6 months after treatment, and total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), hepersensitive C-reactive protein (hs-CRP), left ventricular ejction fraction (LVEF), and flow-mediated dilation (FMD) were also observed before and after treatment. ResultsThe overall efficacy rate in the experimental group at 6 months was 94.3% and in the control group was 88.6% with no significant difference between each other (P>0.05). TG and FMD of patients in the experimental group at 6 months did not significantly change (P>0.05), while LVEF of the experimental group was significantly higher (P<0.05), and hs-CRP, TC, LDL-C, and HDL-C of the experimental group were significantly lower than the control group (P<0.05). ConclusionsShort-term comprehensive efficacy of rosuvastatin for treatment of premature coronary artery disease in patients with acute myocardial infarction is superior to atorvastatin.
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.
目的:觀察阿托伐他汀對抗糖尿病腎病患者腎氧化損傷作用。方法:56例糖尿病腎病患者隨即分為對照組和阿托伐他汀組。對照組給予降糖、降壓等治療,阿托伐他汀組則在對照組治療基礎上加用阿托伐他汀10 mg/d,療程共12周。檢測兩組患者治療前后FBG、BUN、Scr、尿微量白蛋白以及血脂、血清SOD和MDA水平。結果:12周后兩組患者FBG、BUN、Scr、尿微量白蛋白均較治療前下降;與治療前相比,阿托伐他汀組患者血脂水平較治療前明顯改善,同時患者血清SOD活性增,MDA含量下降,二者之間的差異具有顯著性意義。結論:阿托伐他汀除具有降血脂作用外,還可改善糖尿病腎病患者的氧化應激狀態。
Objective To study the effect and mechanism of atorvastatin on improving airway function of mice with chronic obstructive pulmonary disease (COPD) by inhibiting the expression of inducible nitric oxide synthase (iNOS). Methods Wild type (WT) mice were randomly divided into WT control group, WT+COPD group, WT+COPD+atorvastatin group, NC lentivirus group, NC lentivirus+COPD group, NC lentivirus+COPD+atorvastatin group, and iNOS lentivirus+COPD+atorvastatin group. Lung specific iNOS knockout (KO) mice were randomly divided into KO control group and KO+COPD group. The COPD model was established by passive inhalation of cigarette smoke. Atorvastatin (10 mg·kg–1·d–1) was given by gavage, and the negative control (NC) lentivirus or iNOS lentivirus was given by tail vein injection. The lung function indexes including peak inspiratory flow (PIF) and peak expiratory flow (PEF), the number of neutrophils (N), eosinophils (E), lymphocytes (L) and Interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α) in bronchoalveolar lavage fluid (BALF), the expression levels of iNOS, endothelium nitric oxide synthase (eNOS) and neural nitric oxide synthase (nNOS) in lung tissue were measured. Results Compared with WT control group, the levels of PIF and PEF decreased, typical pathological changes of COPD appeared in lung tissue, the numbers of N, E, L and the contents of TNF-α, IL-1β in BALF, the expression of iNOS, eNOS and nNOS in lung tissue increased in WT+COPD group (all P<0.05). After atorvastatin intervention, the levels of PIF and PEF increased, the pathological changes of COPD in lung tissue ameliorated, the numbers of N, E, L and the contents of TNF-α, IL-1β in BALF, the expression of iNOS in lung tissue decreased in WT+COPD+atorvastatin group (all P<0.05). After specific knockout of iNOS in lung tissue, the levels of PIF and PEF increased, the pathological changes of COPD in lung tissue ameliorated, the numbers of N, E, L and the contents of TNF-α, IL-1β in BALF decreased in KO+COPD group (all P<0.05). After overexpression of iNOS by tail vein injection of lentiviral, the levels of PIF and PEF decreased, the pathological changes of COPD in lung tissue aggravated, the numbers of N, E, L and the contents of TNF-α, IL-1β in BALF increased in iNOS lentiviral+COPD+atorvastatin group (all P<0.05). Conclusion The effect of atorvastatin on improving airway function and inflammatory response of COPD mice is related to the inhibition of iNOS expression.
目的 探討阿托伐他汀鈣對頸動脈粥樣硬化患者血管內皮的保護作用。 方法 選取2010年10月－2011年8月頸動脈粥樣硬化患者80例，隨機分為治療組和對照組。對照組給予阿司匹林腸溶片0.1 g，早飯后口服1次；治療組在此基礎上給予阿托伐他汀鈣20 mg，每晚口服1次，10個月為1個療程。分別在治療前后進行頸動脈彩色多普勒超聲檢測頸動脈中膜厚度及頸動脈粥樣硬化斑塊面積，測定甘油三酯（TG）、總膽固醇（TC）、低密度脂蛋白膽固醇（LDL-C）、高密度脂蛋白膽固醇（HDL-C）、一氧化氮（NO）、血管內皮素-1（ET-1）水平。兩組患者在1個療程治療結束后停藥12周，測定TG、TCH、LDL-C、HDL-C、NO、ET-1水平。 結果 與治療前比較，治療組患者的TG、TC、LDL-C、ET-1水平顯著降低，HDL-C、NO水平顯著升高（P＜0.01）。頸動脈中膜厚度和頸動脈粥樣硬化斑塊面積明顯變小（P＜0.05）。對照組無明顯變化。治療組停藥12周后與停藥時比較，TG、TC、LDL-C、ET-1水平顯著升高，HDL-C、NO水平明顯降低（P ＜0.05）。對照組無明顯變化。 結論 阿托伐他汀鈣能顯著改善頸動脈粥樣硬化斑塊患者的血管內皮功能、血脂水平，穩定頸動脈粥樣硬化斑塊，促進斑塊逆轉，且需要長期堅持服用。
目的：探討阿托伐他汀治療高脂血癥患者的療效分析。方法： 對70例確診高脂血癥的患者給予阿托伐他汀10 mg，每日一次，連服3個月，觀察觀察治療前后的血脂、肝功能、腎功能,同時觀察患者有無不良反應。結果：治療3個月后,TC、TG、LDL-C均較治療前顯著下降(Plt;0.05),HDL-C較治療前明顯提高(Plt;0.05),TC、TG、LDL-C、HDL-C治療3個月的總有效率分別是84.28%、74.6%、80%和62.26%,未見明顯不良反應。結論：阿托伐他汀治療高脂血癥患者安全有效。
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.