糖尿病调脂药物治疗的循证医学

本文重点介绍近年来糖尿病患者调脂治疗,主要包括临床常用的他汀类、贝特类、烟酸等药物降胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白-胆固醇(LDL-C)水平、升高高密度脂蛋白-胆固醇(HDL-C),以及减少心血管事件的疗效、不良反应等。     

他汀类药物早期干预对急性冠脉综合征患者血脂、高敏C反应蛋白和纤维蛋白原的影响

目的 比较他汀类药物和阿司匹林联合用药与单用阿司匹林对急性冠脉综合征患者血脂、高敏C反应蛋白及纤维蛋白原的影响。方法 所有患者均在急性冠脉综合征发病后72h内开始接受药物治疗，他汀组(40例)应用他汀类药物加阿司匹林治疗8周，对照组(16例)单用阿司匹林治疗，观察两组总胆固醇、低密度脂蛋白胆固醇、高敏C反应蛋白和纤维蛋白原水平的变化。结果 治疗8周后，他汀组各指标显著降低，面对照组仅高敏C反应蛋白水平显著下降。他汀类药物降低高敏C反应蛋白、纤维蛋白原的程度与其降脂作用无关。结论 他汀类药物与阿司匹林联合用药降低高敏C反应蛋白和纤维蛋白原的作用可能优于单用阿司匹林，并与其抗炎作用有关。     

胆固醇代谢与阿尔茨海默病关系的研究进展

在阿尔茨海默病(AD)发病机制中,占主导地位是Aβ瀑流学说:由于淀粉样前体蛋白的代谢紊乱,产生了过量的Aβ42,后者迅速聚集形成寡聚物,启动了Aβ瀑流效应,造成了Aβ的沉积,形成老年斑.越来越多的实验表明,胆固醇在Aβ的产生和异常沉积过程具有重要调节作用,同时Aβ对胆固醇调节也有反馈作用,探讨两者的相互作用和影响有助于AD发病机制的阐明.而与胆固醇代谢密切相关的因素,如载脂蛋白E、调节胆固醇代谢的药物等也成为研究的热点.     

对急性冠状动脉综合征的新认识和治疗对策

近几年来，由于基础实验研究的迅速发展，对急性冠状动脉综合征(ACS)的认识和治疗取得了重大进展。作者就ACS分子生物学和细胞学基础、不稳定斑块的治疗对策、ACS的危险分层及治疗方法作一综述。     

Statins and peripheral neuropathy

Within the past 3 years seven cases of reversible peripheral neuropathy apparently caused by statins have been reported. Here we report seven additional cases associated with long-term statin therapy, in which other causes of neuropathy were thoroughly excluded. The neuropathy was in all cases axonal and with affection of both thick and thin nerve fibers. The symptoms of neuropathy persisted during an observation period lasting from 10 weeks to 1 year in four cases after statin treatment had been withdrawn. We suggest that long-term statin treatment may be associated with chronic peripheral neuropathy. Received: 6 July 1998 / Accepted in revised form: 1 October 1998     

他汀类与抗血小板药联合用药对缺血性脑血管病患者颈动脉粥样硬化的干预作用

目的:探讨缺血性脑血管病患者联合应用他汀类及抗血小板药对颈动脉粥样硬化和脑血管事件的干预作用。方法:选择146例缺血性脑血管病合并颈动脉粥样硬化患者,将其随机分为治疗组和对照组。治疗组74例,应用氟伐他汀(每晚40mg)和拜阿斯匹灵(100mg/d),对照组72例,仅给拜阿斯匹灵(100mg/d)。共随访2年,分别在治疗前,治疗后6月、12月、18月、24月检测血脂,颈动脉内-中膜厚度,颈动脉斑块积分。结果:治疗组平均颈动脉内-中膜厚度和颈动脉斑块积分,治疗前分别为(1.22±0.19)mm和4.4±2.5,治疗后分别为(0.87±0.15)mm和2.8±1.1,治疗前后比较差异具有显著性(P<0.01)。随访结束时,治疗组缺血性脑血管病复发率9.5%,与对照组复发率(26.3%)相比明显下降。结论:联合应用他汀类及抗血小板药能延缓和逆转缺血性脑血管病患者颈动脉粥样硬化的进展,对缺血性脑血管病的复发有很好的预防作用,且不增加脑出血发生率。     

The use of statins in people at risk of developing diabetes mellitus: Evidence and guidance for clinical practice

Reducing low-density lipoprotein cholesterol (LDL-C) levels using statins is associated with significant reductions in cardiovascular (CV) events in a wide range of patient populations. Although statins are generally considered to be safe, recent studies suggest they are associated with an increased risk of developing Type 2 diabetes (T2D). This led the US Food and Drug Administration (FDA) to change their labelling requirements for statins to include a warning about the possibility of increased blood sugar and HbA1c levels and the European Medicines Agency (EMA) to issue guidance on a small increased risk of T2D with the statin class. This review examines the evidence leading to these claims and provides practical guidance for primary care physicians on the use of statins in people with or at risk of developing T2D. Overall, evidence suggests that the benefits of statins for the reduction of CV risk far outweigh the risk of developing T2D, especially in individuals with higher CV risk. To reduce the risk of developing T2D, physicians should assess all patients for T2D risk prior to starting statin therapy, educate patients about their risks, and encourage risk-reduction through lifestyle changes. Whether some statins are more diabetogenic than others requires further study. Statin-treated patients at high risk of developing T2D should regularly be monitored for changes in blood glucose or HbA1c levels, and the risk of conversion from pre-diabetes to T2D should be reduced by intensifying lifestyle changes. Should a patient develop T2D during statin treatment, physicians should continue with statin therapy and manage T2D in accordance with relevant national guidelines.     

Cumulative clinical trial data on atorvastatin for reducing cardiovascular events: the clinical impact of atorvastatin

ABSTRACT

Background: Since the 1990s a multitude of statin trials have definitively demonstrated the ability of statin therapy to reduce the risk of adverse coronary heart disease (CHD) events. Among these, the Atorvastatin Landmarks program – a group of 32 major atorvastatin trials – has assessed the efficacy and safety of atorvastatin across its full dose range and has helped illustrate its effectiveness in treatment of cardiovascular disease and its related disorders and also in non-cardiovascular outcomes.

Scope: This paper will review the major atorvastatin clinical trials and report the important findings and their clinical significance.

Findings: Clinical trials with atorvastatin have established significant reductions in cardiovascular events in patients with and without CHD. Studies show that high-dose atorvastatin will reduce LDL to ≈?70?mg/dL in many patients and improve cardiac outcomes. Current evidence suggests that high-dose atorvastatin can halt and, in some cases, reverse atherosclerotic progression. A study of diabetic patients showed atorvastatin decreased the occurrence of acute CHD events, coronary revascularizations, and stroke. Atorvastatin has been found to be effective for reducing nonfatal myocardial infarctions and fatal CHD in hypertensive patients with three or more additional risk factors. High-dose atorvastatin was found to be effective in reducing risk of recurrent stroke in patients with prior cerebrovascular events, has been shown to benefit patients suffering a recent acute coronary syndrome, and to slow cognitive decline in preliminary studies of patients with Alzheimer's disease. Atorvastatin has been associated with reduced progression of mild chronic kidney disease; however, in a randomized trial of patients with end stage renal disease on hemodialysis, atorvastatin showed no statistically significant benefit. Limitations of this review include lack of generalizablity of the atorvastatin trial data to other statins, lack of head to head outcome trials involving the newer more potent statins, and the relatively short study durations (none exceeded 5 years) when atherosclerosis is typically a decades-long disease.

Conclusion: A compelling body of evidence documents that atorvastatin reduces major cardiovascular events in both secondary and primary prevention of CHD and in a broad range of patients and disease conditions. Furthermore, throughout its dose range, atorvastatin is safe and well tolerated.