他汀与依折麦布联用提升降胆固醇达标率——中国专家修订选择性胆固醇吸收抑制剂临床应用共识（续）

在临床实践中,应用初始剂量他汀治疗后许多高胆固醇血症患者仍不能达标,此时可有两种选择：即增加他汀剂量或联合应用其他调脂药物。大量临床研究表明,他汀剂量加倍后其降胆固醇作用仅增加6％左右,与他汀治疗相关的不良反应也会增加,致使部分患者不能耐受较大剂量的他汀治疗。     

不同调脂方案对冠状动脉介入治疗后胆固醇代谢标志物的影响

目的:探讨不同强化调脂方案对经皮冠状动脉介入(PCI)术后患者胆固醇代谢标志物及其比值的影响。方法:将90例住院已行择期PCI的慢性稳定型冠心病患者随机分为3组,辛伐他汀40mg/d组(SI组)、辛伐他汀20mg/d+依折麦布10mg/d组(SI/EZ组)和阿托伐他汀20mg/d组(AT组),治疗随访12周,观察调脂疗效、胆固醇代谢标志物的变化和药物不良反应。结果:①3种调脂方案均能明显降低LDL-C、TC和TG水平,同时提高HDL-C水平;12周时,SI/EZ组LDL-C降低幅度(32.2%)和TG下降幅度(29.5%)均高于SI组和AT组,但差异无统计学意义。②治疗12周,3组血清胆固醇合成标志物水平均显著下降(均P<0.05),且SI组和AT组下降幅度明显大于SI/EZ组;胆固醇吸收标志物在SI/EZ组下降幅度达到11.9%～20.5%,SI组和AT组胆固醇吸收标志物水平则升高,且AT组升高幅度大于SI组。③3组均未出现有临床意义的肝酶和肌酶升高。结论:小剂量他汀联合依折麦布与较大剂量他汀相比调脂疗效无显著差异,且前者常见不良反应发生率较低,联合治疗可以明显改善患者的胆固醇代谢状况。     

不同剂量他汀类药物联合曲美他嗪治疗冠心病合并高胆固醇血症的临床疗效

目的 探讨不同剂量他汀类药物联合曲美他嗪治疗冠心病合并高胆固醇血症的临床效果。方法 选取2020年7月至2022年2月汕头大学医学院第二附属医院收治的100例冠心病合并高胆固醇血症患者纳入研究对象，按随机数字表法分为大剂量组与小剂量组，各50例。大剂量组患者给予阿托伐他汀40 mg/d联合曲美他嗪治疗，小剂量组患者给予阿托伐他汀20 mg/d联合曲美他嗪治疗。比较两组患者的治疗效果，比较两组患者治疗前后的总胆固醇(TC)、甘油三酯(TG)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)、超敏C反应蛋白(hs-CRP)、脂蛋白相关磷脂酶A2(Lp-PLA2)水平以及不良反应。结果 大剂量组总有效率显著高于小剂量组(χ²=4.883,P <0.05)；两组治疗后TC、TG、LDL-C显著低于治疗前，HDL-C显著高于治疗前(P <0.05)，大剂量组治疗后TC、TG、LDL-C显著低于小剂量组，HDL-C显著高于小剂量组(t=5.672、4.081、5.488、5.719,P <0.05)；两组治疗后hs-CRP、Lp-PLA2显...     

关注联合用药强调合理安全——选择性胆固醇吸收抑制剂临床应用中国专家共识（2013版）正式公布

中华医学会心血管病学分会与中国老年学学会心脑血管病专业委员会,于2013年4月14日正式发布《选择性胆固醇吸收抑制剂临床应用中国专家共识（2013版）》（以下简称《共识》）。《共识》的主要发起人和核心撰稿专家胡大一、史旭波、郭艺芳教授出席了会议,向媒体同仁介绍了《共识》的撰写背景和主要内容,并回答了媒体提问。基于现有研究结论,此次《共识》也就依折麦布的适用症达成以下共识：①主要用于原发性高胆固醇血症的治疗。作为饮食控制以外辅助治疗,可单独或与他汀联合应用于治疗原发性（杂合子家族性或非家族性）高胆固醇血症。治疗纯合子家族性高胆固醇血症时可联合应用依折麦布与他汀。治疗纯合子谷甾醇血症（或植物甾酵血症）时可作为饮食控制以外的辅助治疗;②高胆固醇血症患者经常规剂量他汀治疗后胆固醇水平仍不能达标者,可联合应用依折麦布;③不适于或不能耐受他汀治疗的高胆固醇血症患者,可应用依折麦布治疗;④中重度高胆固醇血症患者可起始联合应用依折麦布与常规剂量他汀治疗;⑤与贝特类或烟酸类药物联合用于混合型血脂异常患者：⑥与常规剂量他汀联合用于慢性肾脏疾病患者预防心血管事件;⑦应用由他汀与依折麦布组成的单片复方制剂可简化治疗方案,提高患者长期治疗的依从性,对于有适应证的患者推荐首先选用。     

胆固醇吸收抑制剂临床应用中国专家共识

在近期举行的《胆固醇吸收抑制剂临床应用中国专家共识》（以下简称《共识》）新闻发布会上获悉：“调脂治疗我们有了更丰富的手段,对于单独应用他汀类药物胆固醇水平不能达标或不能耐受较大剂量他汀治疗的患者,联合应用他汀和依折麦步可显著降低LDL-C水平,而不良反应没有明显增加。”     

依折麦布联合瑞舒伐他汀对低密度脂蛋白胆固醇未达标的急性冠脉综合征患者胆固醇代谢的影响

目的探析依折麦布联合瑞舒伐他汀(可定)对低密度脂蛋白胆固醇未达标的急性冠脉综合征患者胆固醇代谢的影响。方法采用随机数字表法将2016-02~2017-02收治的210例低密度脂蛋白胆固醇未达标的急性冠脉综合征患者分为对照组(瑞舒伐他汀治疗)及观察组(依折麦布联合瑞舒伐他汀治疗)各105例持续治疗12周,对两组胆固醇代谢影响效果进行比较。结果观察组不良反应总发生率为6.67%,与对照组4.76%比较,差异无统计学意义(P0.05)。治疗前两组胆固醇代谢指标无明显差异,治疗后观察组各指标数值优于对照组,差异有统计学意义(P0.05)。结论在低密度脂蛋白胆固醇未达标的急性冠脉综合征患者治疗中依折麦布联合瑞舒伐他汀改善胆固醇代谢效果更佳,可作为优选方案推广使用。     

大剂量瑞舒伐他汀联合普罗布考对冠心病合并高胆固醇血症患者的疗效观察

目的观察大剂量瑞舒伐他汀联合普罗布考对冠心病(CHD)合并高胆固醇血症患者临床疗效的影响。方法从2018年1月至2019年1月来院就诊的CHD合并高胆固醇血症患者中共选取符合要求的患者120例,采用随机数字表法分为大剂量组(瑞舒伐他汀片20mg、每晚一次)、联合组(瑞舒伐他汀片10mg、每晚一次+普罗布考片250mg、每天2次),每组各60例,治疗3个月。将相应的总胆固醇(TC)、低密度脂蛋白胆固醇(LDL-C)数值以及药物疗效、不良反应发生的概率做好相应的记录。结果联合组的治疗有效率95.00%,显著高于大剂量组的81.70%(P0.05)。经过为期三个月的治疗后,两组患者的TC、LDL-C均有所减少,但联合组降幅更大(P0.05)。联合组不良反应少于大剂量组,但组间差异无统计学意义(P0.05)。结论相比大剂量瑞舒伐他汀治疗,常规剂量联合普罗布考的方案对于CHD合并高胆固醇的患者来说,疗效明显且具有较高的安全性。     

调脂进程中的困惑与期望

本文讲述了他汀类药问世以来,调脂进程中的困惑与期望.简述了尽管他汀类药在防治心血管病方面取得了辉煌成就,但有局限性.他汀剂量加倍,低密度脂蛋白胆固醇(LDL-C)水平的降幅只能再增加6%,其荻益有限,而不良反应明显增加.用大剂量他汀长期治疗后仍然有70%～80%的临床事件未获得改善.近几年来,为进一步提高调脂疗效的努力,如新药开发未见进展;联合用药(如ENHANCE研究)虽明显降低了LDL-C水平,但未能抑制动脉粥样硬化(CIMT)的进展,心血管事件也未见增益;用胆固醇酯转移酶抑制剂-Torcetrapib进行的几个升高高密度脂蛋白胆固醇(HDL-C)的研究,虽然明显升高HDL-C水平,非但都未能抑制动脉粥样硬化的进展,反而使心血管事件和全因死亡上升都明显增加.这些研究结果,令学者感到困惑,使临床医生感到不知所措.现有理念在实践中遇到众多困惑,新理论尚不成熟的当前,作者认为,在调脂进程中,应用创新思维,深入探索降低LDL-C及升HDL-C的有关问题.作者对目前调脂治疗的总体思考,提了六点意见,以便讨论.     

普罗布考与阿托伐他汀联合用药对冠心病合并高胆固醇血症患者血脂与心绞痛发作的影响

目的比较普罗布考与阿托伐他汀单独及联合应用对冠心病合并高胆固醇血症患者血脂及心绞痛发作的影响。方法将119例冠心病合并高胆固醇血症患者随机分成普罗布考组、阿托伐他汀组及普罗布考与阿托伐他汀联合应用组,普罗布考剂量为0.5g,bid;阿托伐他汀剂量为10mg,qd。比较用药前和12周后三组患者平板运动心电图试验、血脂、氧化型低密度脂蛋白、超氧化物歧化酶和丙二醛等指标变化。结果三组血清总胆固醇水平(P<0.001)和低密度脂蛋白胆固醇水平(P<0.01)均明显降低;阿托伐他汀组高密度脂蛋白胆固醇增高(P<0.01),而氧化型低密度脂蛋白、超氧化物歧化酶和丙二醛变化不明显;普罗布考组氧化型低密度脂蛋白和丙二醛显著降低(P<0.001),超氧化物歧化酶升高(P<0.001),但高密度脂蛋白胆固醇降低(P<0.01);联合用药组氧化型低密度脂蛋白和丙二醛显著降低(P<0.001),超氧化物歧化酶升高(P<0.001),高密度脂蛋白胆固醇变化不明显。三组治疗后平板运动心电图试验阳性率和研究结束前2周内心绞痛发作次数均减少,普罗布考组较阿托伐他汀组更明显(P<0.05),联合用药组更为显著(P<0.01)。结论普罗布考为一安全有效的降血脂及减少心绞痛发作的药物,与阿托伐他汀联合应用安全,疗效更显著。     

瑞舒伐他汀与辛伐他汀治疗老年冠心病伴高胆固醇血症的临床对比

目的比较瑞舒伐他汀与辛伐他汀治疗老年冠心病伴高胆固醇血症的临床疗效及安全性。方法老年冠心病伴高胆固醇血症患者132例,按随机数字法分为观察组和对照组,各66例,观察组予以瑞舒伐他汀治疗,对照组予以辛伐他汀治疗,比较两组患者治疗后的血脂水平、颈动脉斑块面积及药物不良反应发生情况。结果观察组患者治疗后低密度脂蛋白胆固醇(LDL-C)、总胆固醇(TC)明显低于对照组(P0.05),但两组患者治疗后甘油三酯(TG)、高密度脂蛋白胆固醇(HDL-C)无明显差异(P0.05)。观察组患者治疗后颈动脉斑块面积、颈动脉内膜-中膜厚度较治疗前及对照组治疗后明显降低(P0.05)。观察组不良反应发生率为6.06%,远低于对照组的18.18%(P0.05)。结论瑞舒伐他汀治疗老年冠心病伴高胆固醇血症患者降脂效果显著,安全性高。     

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??Abstract??Cholesterol lowing treatment is one of important parts in the therapy of atherosclerosis.Clinical research demonstrated that the statins treatment combined with therapeutic lifestyle changes can prevent the genesis and development of atherosclerosis.Aim to achieve ideal LDL-C target level and reduce adverse effects of statins??the combination of cholesterol absorption inhibitors and statins could play a significant role in the therapy of atherosclerosis.     

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多廿烷醇是一种新型调脂药,可以抑制胆固醇合成及提高低密度脂蛋白的血液清除率.降脂效果与他汀类药物相似,对于特殊人群如老年人、肝病患者,其临床有效性、安全性和耐受性已经为多个临床研究证实.与他汀类、贝特类药物联合应用安全性良好.可作为高胆固醇血症、高低密度脂蛋白胆固醇血症或低高密度脂蛋白胆固醇血症患者一级预防治疗用药和不能耐受其他降脂药物的二级预防治疗用药.多廿烷醇对动脉粥样硬化危险因素的长期临床作用还需要进一步研究.     

The clinical effect and tolerability of ezetimibe in high-risk patients managed in a specialty cardiovascular risk reduction clinic

INTRODUCTION: Ezetimibe (EZ) is a selective cholesterol absorption inhibitor approved for use in Canada. The effect and tolerability of EZ among patients was evaluated in the clinical setting of a specialty cardiovascular risk reduction clinic at the University of Alberta Hospital, Edmonton, Alberta. patients and METHODS: All patients 18 years of age or older who were prescribed EZ were included, unless they failed to take EZ for a minimum of two weeks, did not have baseline and on-EZ low-density lipoprotein cholesterol (LDL-C) levels, or had concomitant lipid-lowering drugs or dosages changed within one month of starting EZ. RESULTS: Eighty-four patients (mean age 57.9 years) were included. By Framingham risk calculation, 71.4% were found to be high-risk patients, 13.1% moderate-risk patients and 15.5% low-risk patients; 66.7% of patients had prior cardiovascular events. On EZ, the mean reductions were: total cholesterol level 1.11 mmol/L (16.5%); LDL-C level 1.01 mmol/L (22.3%); high-density lipoprotein cholesterol level 0.06 mmol/L (4.6%); and ratio of total cholesterol level to high-density lipoprotein cholesterol level 0.68 mmol/L (12.8%); all were statistically significant (P<0.001). Results were similar when stratified by primary (n=28) versus secondary (n=56) prevention. Patients on EZ monotherapy (n=34) had mean LDL-C reductions of 1.03 mmol/L (20.5%) compared with 1.19 mmol/L (30.1%) or 0.95 mmol/L (22.5%), where EZ was added to low-dose or high-dose statins (P<0.01 for all). On EZ, 30 patients (35.7%) achieved previously unattainable target LDL-C levels. Four patients discontinued the drug due to side effects. CONCLUSIONS: EZ is safe and effective in high-risk patients treated in the clinical setting of a cardiovascular risk reduction clinic. A mean LDL-C reduction of 1 mmol/L (20% to 30%) in all patient subgroups is consistent with previous clinical trial results. The significant reduction in LDL-C (mean 22.5%) observed in the EZ plus high-dose statin subgroup provides clinical evidence for use of this medication beyond published studies.     

依折麦布联合普伐他汀治疗高胆固醇血症患者的疗效

目的探索依折麦布联合普伐他汀治疗高胆固醇血症的临床疗效。方法选择符合高胆固醇血症的患者180例,男女各90例,在合理的饮食、生活习惯和体育运动下,分为三组,每组男女平衡：A组为单用依折麦布治疗组60例：B组为单用普伐他汀治疗组60例;C组为依折麦布联合普伐他汀治疗组60例。观察三组血清总胆固醇（total cholesterol,TC）、低密度脂蛋白胆固醇（low-density lipoprotein cholesterol, LDL-C）、高密度脂蛋白胆固醇（high—density lipoprotein cholesterol,HDL—C）、载脂蛋白B（apoprotein B,Apo—B）及三酰甘油（triacylglycerol,TG）等治疗前、后的变化,并记录不良反应。结果三组治疗后血清TC、LDL—C、Apo-B、TG浓度均能降低,血清HDL—C浓度均能升高,但以C组更明显（P〈0．05）;C组总有效率达91．7％,优于A、B组。结论依折麦布联合普伐他汀具有良好的药物协同效应,可有效调节胆固醇代谢,效果明显优于单独使用,可避免大剂量他汀类药物的不良反应。     

Conceptual foundations of the UCSD Statin Study: a randomized controlled trial assessing the impact of statins on cognition, behavior, and biochemistry

BACKGROUND: Statin cholesterol-lowering drugs are among the most prescribed drugs in the United States. Their cardiac benefits are substantial and well supported. However, there has been persistent controversy regarding possible favorable or adverse effects of statins or of cholesterol reduction on cognition, mood, and behavior (including aggressive or violent behavior). METHODS: The literature pertaining to the relationship of cholesterol or statins to several noncardiac domains was reviewed, including the link between statins (or cholesterol) and cognition, aggression, and serotonin. RESULTS: There are reasons to think both favorable and adverse effects of statins and low cholesterol on cognition may pertain; the balance of these factors requires further elucidation. A substantial body of literature links low cholesterol level to aggressive behavior; statin randomized trials have not supported a connection, but they have not been designed to address this issue. A limited number of reports suggest a connection between reduced cholesterol level and reduced serotonin level, but more information is needed with serotonin measures that are practical for clinical use. Whether lipophilic and hydrophilic statins differ in their impact should be assessed. CONCLUSION: There is a strong need for randomized controlled trial data to more clearly establish the impact of hydrophilic and lipophilic statins on cognition, aggression, and serotonin, as well as on other measures relevant to risks and quality-of-life impact in noncardiac domains.     

Comparison of the efficacy and tolerability of simvastatin and atorvastatin in the treatment of hypercholesterolemia

BACKGROUND: Simvastatin and atorvastatin are effective statins for treating hypercholesterolemia. HYPOTHESIS: The study was undertaken to compare the efficacy and tolerability of simvastatin 20 and 40 mg/day and atorvastatin 10 and 20 mg/day. METHODS: In this multinational, open-label, crossover study, 258 patients with primary hypercholesterolemia were randomized after 4 weeks of diet plus placebo to once-daily administration of a starting dose sequence of simvastatin (20 mg) or atorvastatin (10 mg), or a higher dose sequence of simvastatin (40 mg) or atorvastatin (20 mg) for 6 weeks. Patients were then switched after a 1-week washout to the corresponding starting or higher dose of the alternate drug for a second 6-week period. The primary endpoint was the mean percent change from baseline to Week 6 in low-density lipoprotein (LDL) cholesterol; percent changes from baseline in total cholesterol, high-density lipoprotein cholesterol, triglycerides, and apolipoprotein B were also compared. Safety was assessed through adverse experiences and laboratory measurements. RESULTS: Both statins produced statistically significant improvements in all measured plasma lipids and lipoproteins. The main treatment comparison showed no statistically significant difference in changes in LDL cholesterol and triglycerides, whereby the overall effects were comparable when doses of 20 mg and 40 mg of simvastatin were compared with atorvastatin 10 mg and 20 mg. The mean percent reductions for LDL cholesterol from baseline to Week 6 ranged from 35-42% for the entire study cohort. An LDL cholesterol level < or = 130 mg/dl (3.4 mmol/l) was achieved in approximately 70% of patients treated with both drugs in this study. Simvastatin and atorvastatin were well tolerated at the doses studied. CONCLUSION: In patients with hypercholesterolemia, the most commonly used doses of simvastatin and atorvastatin produced similar changes in LDL cholesterol and achieved an LDL cholesterol level < or = 130 mg/dl (3.4 mmol/l) in a similar number of patients. Both statins were well tolerated.     

Management of hyperlipidemia in the pediatric population

Opinion statement Heterozygous familial hypercholesterolemia (FH) affects one in every 500 persons and is the most common cause of markedly elevated cholesterol levels in children. Other causes of primary hyperlipidemia include familial combined hyperlipidemia, which is also common (approximately 1%) but not usually manifest until after puberty, and very rare genetic disorders that may lead to severe hypertriglyceridemia and chylomicronemia syndrome. In children with heterozygous FH, the short-term risk of clinical events is low; therefore, management starts with stratification of risk, followed by dietary modification, and in high-risk cases, pharmacologic treatment initiated after puberty. Male gender, a family history of premature coronary heart disease, and level of low-density lipoprotein (LDL) cholesterol above 4.9 mmol/L are important determinants of risk. Trials have shown that statins effectively lower LDL cholesterol levels; in one study, statins restored endothelial function, with no clinically adverse effects. The effects of statins for longer than 2 years have not been studied. The use of bile acid sequestrants (resins) is limited by compliance and side effects. Children with homozygous FH require expert management with LDL apheresis, high doses of effective statins, and cardiologic follow-up. Ezetimibe, the first in a new class of cholesterol absorption inhibitors, may provide additional efficacy in homozygous FH.     

Kardiovaskul?res Risiko und medikament?se Lipidtherapie

Patients with type 2 and advanced type 1 diabetes bear a very high risk for cardiovascular disease, which is substantially driven by the associated dyslipidemia; therefore, patients with diabetes clearly benefit from intensive lipid-lowering therapy. To ensure optimal risk reduction, lipid-lowering therapy must consistently aim at and achieve the recommended target values. Statins reduce low-density lipoproteins (LDL) and non-high-density lipoprotein (HDL) cholesterol and are the mainstay of lipid-lowering therapy also in diabetes patients but highly potent statins are often applied to reach the goals. Ezetimib and bile acid sequestrants also lower cholesterol levels and may be given in combination with statins or to statin-intolerant patients. Fibrates effectively lower serum triglycerides and provide clinical benefits in patients with concurrent low HDL cholesterol levels. Nicotinic acid and long-chain ??3 fatty acids could provide improvements due to HDL cholesterol elevation, anti-arrhythmic and other effects.     

Statins: beneficial or adverse for glucose metabolism

Large-scale clinical trials have established that statin use for lowering blood cholesterol is beneficial in reducing atherosclerotic cardiovascular diseases in different populations. However, the general reputation of statins seems to be clouded by a potential adverse effect of a class of statins on glucose metabolism. This paper reviewed clinical data of statins regarding the effects on diabetes mellitus and glucose metabolism. At least five randomized controlled studies, primarily investigating the protective effect of statins on the risk of cardiovascular diseases, have addressed the effect of statins on glucose metabolism in Western countries. One study showed that pravastatin (40 mg/day) was protective against the development of diabetes mellitus. Two studies of atorvastatin (10 mg/day) and one study of simvastatin (40 mg/day) showed no measurable effect of these regimens on the risk of diabetes mellitus or the clinical course of diabetes mellitus. One study of atorvastatin (80 mg/day) versus pravastatin (40 mg/day) suggested a deterioration of glucose metabolism associated with a high dose of atorvastatin. In Japan, a few case reports have noted a potential adverse effect of atorvastatin on glycemic control in patients with diabetes mellitus; however, seven clinical trials have showed no such effect of atorvastatin although these studies were relatively small in size and short in follow-up. Only one of the two observational studies suggested a possible adverse effect of atorvastatin on glycemic control. Evidence is extremely limited regarding atorvastatin use and deterioration in glycemic control, and further studies are needed to draw a conclusion on this issue.