阿托伐他汀钙与阿昔莫司联用的临床药理学研究进展

阿托伐他汀是目前临床上广泛使用的口服调脂药,主要通过降低甘油三酯和低密度脂蛋白发挥作用,但其疗效及个体差异大.广谱调脂药阿昔莫司主要降低总胆固醇,提高高密度脂蛋白水平,但副作用较明显,限制其临床使用.用单一调脂药临床效果不明显,而联用他汀类和烟酸类调脂药效果优于单用.本文对阿托伐他汀与阿昔莫司联合应用的临床药理学特征进行综述.     

他汀类药物时代烟酸调脂临床应用评价和思考

烟酸属水溶性B族维生素,其在大剂量使用时具有广谱的调脂作用。在他汀类调脂药物上市之前,烟酸及其缓释剂是较常用的调脂药物之一。在他汀类药物上市之后,多项大规模随机对照的临床研究已证实他汀在有效降低胆固醇的同时可显著减少心血管事件的发生率和死亡率,目前他汀已成为动脉粥样硬化相关疾病防治的首选降脂药物。本文综述了他汀时代烟酸调脂治疗的临床研究、荟萃分析和近年血脂异常管理指南对烟酸的应用建议,为今后烟酸的临床应用和研究提供参考。     

2013年门诊口服调脂药处方分析

目的:研究门诊口服调脂药的临床使用情况.方法:随机抽取门诊2013年上半年的处方12000张,其中含有调脂药的处方2106张,对患者的用药频度、联合用药等进行统计、分析.结果:发现2106张处方中,他汀类出现的频率最高,使用频率最少的是烟酸片.结论:门诊口服调脂药的使用情况基本稳定,临床治疗用药以他汀类调脂药为主.     

依折麦布联合他汀类药物降脂新进展

目前他汀类药物成为常用调脂药物,能有效降低低密度脂蛋白胆固醇（low-density lipoprotein cholesterol,LDL-C）水平,然而,他汀类药物单用时,并不能使所有冠心病患者的LDL-C降至目标值,因此,临床上需要考虑调脂药物联合用药。他汀类与贝特类药物联用时,肝脏毒性反应和肌病发生的危险性增大;而他汀类与烟酸类药物联用,患者的耐受性差,故上述联合用药方案难以广泛应用。     

2006～2008年我院调脂药应用分析

目的：分析调脂药的使用情况及用药趋势,促进合理用药。方法：对2006～2008年上海交通大学医学院附属仁济医院常用调脂药的销售金额、用药频度、年均增长率以及日用药金额进行统计分析。结果：调脂药的销售金额和DDDs呈逐年上升趋势。其中,他汀类药始终列第l位,其次是贝特类和烟酸类。结论：他汀类是临床上主要的调脂药,总体用药情况较合理。     

阿托伐他汀联合缓释烟酸的调脂及抗颈动脉硬化的疗效分析与评价

目的探讨阿托伐他汀联合缓释烟酸对冠心病患者血脂调节和防止动脉硬化的影响。方法选择冠心病患者86例,随机分成两组,对照组每晚口服阿托伐他汀10mg,治疗组每晚联合口服缓释烟酸(阿昔莫司)500mg和阿托伐他汀10mg。观察两组患者的调脂和消除颈动脉斑块的疗效及安全性。结果两组患者治疗前后血脂变化及颈动脉斑块消退程度相比较,差异均有统计学意义(P<0.05)。结论两种治疗方法均有明显的降脂作用。缓释烟酸对升高高密度脂蛋白胆固醇作用更明显,联合缓释烟酸更有利于全面调脂,延缓颈动脉粥样硬化。     

阿托伐他汀联合缓释烟酸的调脂及抗颈动脉硬化的疗效分析与评价

目的 探讨阿托伐他汀联合缓释烟酸对冠心病患者血脂调节和防止动脉硬化的影响.方法 选择冠心病患者86例,随机分成两组,对照组每晚口服阿托伐他汀10mg,治疗组每晚联合口服缓释烟酸(阿昔莫司)500mg和阿托伐他汀10mg.观察两组患者的调脂和消除颈动脉斑块的疗效及安全性.结果 两组患者治疗前后血脂变化及颈动脉斑块消退程度相比较,差异均有统计学意义(P＜0.05).结论 两种治疗方法均有明显的降脂作用.缓释烟酸对升高高密度脂蛋白胆固醇作用更明显,联合缓释烟酸更有利于全面调脂,延缓颈动脉粥样硬化.     

糖尿病冠心病调脂药物干预结果评价

充分的循证医学证据证明,调脂治疗在糖尿病冠心病患者中有较大获益。调脂治疗的最终目的是干预动脉粥样硬化的进程,降低终点事件。近年来各大权威指南推荐低密度脂蛋白胆固醇（LDL—C）是血脂干预的首要目标。目前临床上供选用的调脂药物有他汀类、贝特类、烟酸类、树脂类、胆固醇吸收抑制剂等。其中．他汀类药物在糖尿病冠心病调脂治疗中的领导地位基本确立。在LDL—C达标后,若仍存在高三酰甘油血症或低高密度脂蛋白胆固醇血症．可合并使用贝特类或烟酸类调脂药．     

高胆固醇血症患者服用他汀类药物后血清触珠蛋白水平变化的初步研究

目的:分析高胆固醇血症患者服用他汀类调脂药前后血清触珠蛋白(haptoglobin,Hp)水平的变化,探讨其与他汀类药物治疗的关系和临床意义。方法:入组原发性高胆固醇血症患者32例,分别服用洛伐他汀/烟酸缓释片(10 mg/500 mg.d-1)和匹伐他汀(2 mg.d-1),治疗8周后,观察药前、药后血清Hp水平的变化。结果:高胆固醇血症患者分别服用2种他汀类调脂药物后,两组Hp水平均高于治疗前(P<0.05)。其中,服用洛伐他汀/烟酸缓释片的患者,Hp增加了17.87%;服用匹伐他汀的患者,Hp增加了19%。结论:服用他汀药物后,高胆固醇血症患者的血清Hp水平增加。     

调脂药的分类及用药原则

正高脂血症是动脉粥样硬化和冠心病的重要危险因素,而冠心病常可并发心绞痛及心肌梗死。那么如何合理应用调脂药物,防治高脂血症呢?本文就调脂药的应用进行简单的阐述,仅供参考。1.常用调脂药分类及其代表药物是哪些?(1)HMG-Co A还原酶抑制剂:包括氟伐他汀、阿托伐汀等;(2)烟酸类:包括阿西莫司、烟酸等;(3)纤维酸衍生物:包括非诺贝特、吉非贝齐等;(4)胆汁酸结合剂:包括考来     

Statins and pregnancy: between supposed risks and theoretical benefits

Cardiovascular diseases are the leading cause of mortality in industrialized countries. Treatment with statins is effective in primary prevention in patients at high cardiovascular risk. Statins are inhibitors of hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase and are classed as lipid-lowering drugs. In 2010, atorvastatin was the biggest-selling drug in the world ($US10.73?billion). Increases in the average age of pregnant women and in the prevalence of morbid obesity have inevitably led to exposure to statins in certain women during the first trimester of pregnancy. The teratogenic risk attendant upon use of statins is unclear because the available data are contradictory, but statins remain contraindicated in pregnant women. The benefits of statins in prevention of cardiovascular risk may not be solely due to their cholesterol-lowering effects: the so-called pleiotropic effects of vascular protection lead some experts to posit a potential benefit in the management of preeclampsia. In this review we evaluate the theoretical benefits and supposed risks of statins in pregnant women. After a brief overview of the pharmacodynamic properties of statins, we address the question of the teratogenic risk of statins, and then detail the rationale for the therapeutic potential of statins in preeclampsia.     

他汀类药物肝脏安全性的研究进展及合理选用

随着他汀类药物在临床上的广泛使用,他汀类药物的安全性问题也一直备受关注,最常见的问题是血清转氨酶升高。临床对他汀类药物肝脏安全性的认识不足可能限制他汀类药物的一级和二级预防和治疗应用。本文通过对他汀类药物的说明书、相关指南及文献的查阅和分析,总结了他汀类药物肝脏安全性的研究进展,为临床正确认识他汀类药物肝脏安全性及合理选用提供参考。     

他汀类药物代谢相关基因多态性与其不良反应发生的相关性

目的:为他汀类药物的临床精准用药,预防和减少不良反应(ADR)的发生提供参考。方法:收集近年来国内外有关他汀类药物基因多态性与其ADR的参考文献,对他汀类基因多态性与其ADR的相关性进行归纳和总结。结果:药物代谢酶和转运体的相关基因多态性是影响他汀类药物ADR发生的重要因素。结论:基因多态性研究可为预防他汀类药物的ADR提供参考依据,临床可在服用他汀类药物前对患者进行基因型检测,以降低ADR的发生率。     

Statins and osteoporosis: new role for old drugs

Osteoporosis is the most common bone disease, affecting millions of people worldwide and leading to significant morbidity and high expenditure. Most of the current therapies available for its treatment are limited to the prevention or slowing down of bone loss rather than enhancing bone formation. Recent discovery of statins (HMG-CoA reductase inhibitors) as bone anabolic agents has spurred a great deal of interest among both basic and clinical bone researchers. In-vitro and some animal studies suggest that statins increase the bone mass by enhancing bone morphogenetic protein-2 (BMP-2)-mediated osteoblast expression. Although a limited number of case-control studies suggest that statins may have the potential to reduce the risk of fractures by increasing bone formation, other studies have failed to show a benefit in fracture reduction. Randomized, controlled clinical trials are needed to resolve this conflict. One possible reason for the discrepancy in the results of preclinical, as well as clinical, studies is the liver-specific nature of statins. Considering their high liver specificity and low oral bioavailability, distribution of statins to the bone microenvironment in optimum concentration is questionable. To unravel their exact mechanism and confirm beneficial action on bone, statins should reach the bone microenvironment in optimum concentration. Dose optimization and use of novel controlled drug delivery systems may help in increasing the bioavailability and distribution of statins to the bone microenvironment. Discovery of bone-specific statins or their bone-targeted delivery offers great potential in the treatment of osteoporosis. In this review, we have summarized various preclinical and clinical studies of statins and their action on bone. We have also discussed the possible mechanism of action of statins on bone. Finally, the role of drug delivery systems in confirming and assessing the actual potential of statins as anti-osteoporotic agents is highlighted.     

Statin therapy and myocardial no-reflow

HMG-CoA reductase inhibitors (statins) have now become one of the most powerful pharmacological strategies in the treatment of cardiovascular diseases. Originally, the cardioprotective effects of statins were thought to be mediated through lipid lowering actions. However, it has now become increasingly clear that the beneficial effects of statins are not related to the lipid lowering effects, but rather to a number of pleiotropic actions. Of particular interest, statins have been shown to increase bioavailability of nitric oxide and protect against vascular inflammation and cardiac cell death in a number of cardiovascular disease states. In this present issue of the British Journal of Pharmacology, Zhao and colleagues provide a novel mechanism of action for statins with the observation that simvastatin reduces myocardial 'no-reflow' after ischemia and reperfusion by activating the mitochondrial K(ATP) channel. The findings of the present study have very profound implications for the treatment of cardiovascular disease. This commentary discusses the implications of these findings and how they relate to the established cardioprotective actions of statins.     

Statin treatment and the natural history of atherosclerotic-related diseases: pathogenic mechanisms and the risk-benefit profile

Large-scale intervention trials demonstrate that treatment with statins, the most effective lipid lowering drug class, significantly reduces the risk of coronary heart disease events. Recent evidence suggests that more aggressive LDL cholesterol lowering with newly developed statins may provide greater clinical benefit, even in individuals with moderately elevated serum cholesterol levels. There is increasing evidence that statins exert a myriad of other beneficial pleiotropic effects on the vascular wall, thus altering the course of atherosclerotic disease. In the long-term treatment, non-life-threatening side effects may occur in up to 15% of patients receiving one statin. Significant elevations in the activity of serum aminotransferase and creatine kinase alone or in combination with muscle pain in statin-treated patients should be taken seriously. The combination of the statins with gemfibrozil results in higher rates of drug toxicity. Reports show possible adverse effects of statins on nervous system function including mood alterations, however, statins have also been associated with improvement in central nervous system disorders. Special attention must be paid to the tolerability of the statins in children, elderly and transplant patients. Future clinical studies and surveillance information will warrant long term safety of each member of this class of lipid-lowering agents. New classes of patients with diabetes, metabolic syndrome and renal diseases may have clinical benefits from statins. New upcoming clinical trials will address the fundamental question of whether statin treatment can protect from the natural history of atherosclerotic-related diseases. This will require a more prolonged follow-up (i.e., 10 to 15 years). Finally, the basic understanding of newer pathogenic mechanisms involving the effects of statins on angiogenesis and the nitric oxide pathway should be explored in the clinical setting as well as the study of pathogenic mechanisms by which statins can affect plaque instability.     

Statins and muscle pain

ABSTRACT

Introduction: Statins remain among the most frequently prescribed drugs and constitute a cornerstone in the prevention of cardiovascular disease. However, muscle symptoms are often reported from patients on statins. Muscle symptoms are frequently reported as adverse events associated with statin therapy.

Areas covered: In the present narrative review, statin-associated muscle pain is discussed. It elucidates potential mechanisms and possible targets for management.

Expert opinion: In general, the evidence in support of muscle pain caused by statins is in some cases equivocal and not particularly strong. Reported symptoms are difficult to quantify. Rarely is it possible to establish a causal link between statins and muscle pain. In randomized controlled trials, statins are well tolerated, and muscle-pain related side-effects is similar to placebo. There are also nocebo effects of statins. Exchange of statin may be beneficial although all statins have been associated with muscle pain. In some patients reduction of dose is worth trying, especially in primary prevention Although the benefits of statins outweigh potential risks in the vast majority of cases, careful clinical judgment may be necessary in certain cases to manage potential side effects on an individual basis.     

高脂血症人群使用他汀类药物情况调查分析

目的了解高脂血症人群他汀类药物使用情况及其与《中国成人血脂异常防治指南（2007）》（简称《指南》）的差距。方法收集2012年本院2000名体检者的相关资料,统计符合《指南》药物治疗标准的人数;统计符合《指南》药物治疗标准实际服用他汀类药物治疗人数和未治疗人数。结果2000名体检者中,649名应服用他汀类药物治疗,占32．5％,实际服用他汀类药物96名,服用率为14．8％。极高危服用率为58．4％,高危服用率为28．8％,中危服用率为6．4％,低危服用率为5。4％。结论高脂血症人群他汀类药物使用率较低,与《指南》要求差距甚远,应重点关注。     

Synthetic statins: more data on newer lipid-lowering agents

Extensive trial evidence supports the use of hydroxy-methyl-glutaryl-CoA reductase inhibitors (HMG-CoA-RI; statins) in atherosclerotic disease. Statins can be divided into two broad groups: the 'natural' statins derived from a fungal metabolites, and synthetic compounds. Whether all statins have similar anti-atherosclerotic properties, or whether these actions are specific to the 'natural' statins, is controversial. This commentary reviews the differences between natural and synthetic statins with regard to lipid-lowering and non-lipid-lowering effects, including their action on the acute phase reactant C-reactive protein. Among the newer synthetic statins, fluvastatin has some positive end-point evidence while cerivastatin shares many biochemical properties with the 'natural' statins. Extensive clinical trial programmes are underway with both atorvastatin and cerivastatin. These trials will give a definitive answer to the question of whether synthetic statins are as equally efficacious as 'natural' statins in preventing atherosclerotic events.