Shaw Steven M, Fildes James E, Yonan Nizar, Williams Simon G
North West Regional Cardiac and Transplant Unit, University of South Manchester NHS Foundation Trust, Manchester, UK.
Cardiology. 2009;112(1):4-12. doi: 10.1159/000137692. Epub 2008 Jun 25.
HMG-CoA (3-hydroxy-3-methylglutaryl coenzyme A) reductase inhibitors, or 'statins', have revolutionized the management of patients with atherosclerotic vascular disease. Following 2 large acute coronary syndrome trials, additional clinical benefit outside their effect of low-density lipoprotein (LDL) lowering was proposed. This concept was introduced following the observation of cardiovascular event rate reduction, only weeks after initiation of treatment and supposedly before the effect of LDL lowering could have influenced atheroma volume burden. Furthermore, there has been a substantial compilation of experimental data demonstrating beneficial effects of statins on inflammation, thrombosis, platelet aggregation, immunomodulation and endothelial function. These are hypothesized to occur via the interruption of the mevalonate pathway. However, the absolute benefit of these non-lipid-lowering effects, often referred to as 'pleiotropic effects', has been challenged by meta-analysis data. Anti-inflammatory actions have also been proposed to occur by the process of LDL lowering alone rather than due to a unique property of statins. Furthermore, some experimental data reports have shown evidence of pleiotropic effects in non-statin lipid-modifying agents. In this review article, we consolidate what is known so far and critically analyse the literature in order to highlight the outstanding issues.
HMG-CoA（3-羟基-3-甲基戊二酰辅酶A）还原酶抑制剂，即“他汀类药物”，彻底改变了动脉粥样硬化性血管疾病患者的治疗方式。在两项大型急性冠状动脉综合征试验之后，人们提出了除降低低密度脂蛋白（LDL）作用之外的其他临床益处。这一概念是在观察到治疗开始仅几周后心血管事件发生率降低之后提出的，而且据推测在LDL降低的作用可能影响动脉粥样硬化体积负担之前就已出现这种情况。此外，已经有大量实验数据汇编表明他汀类药物对炎症、血栓形成、血小板聚集、免疫调节和内皮功能具有有益作用。据推测这些作用是通过甲羟戊酸途径的中断而发生的。然而，这些非降脂作用（通常称为“多效性作用”）的绝对益处受到了荟萃分析数据的质疑。抗炎作用也被认为仅通过降低LDL的过程发生，而不是由于他汀类药物的独特特性。此外，一些实验数据报告显示在非他汀类脂质修饰剂中也存在多效性作用的证据。在这篇综述文章中，我们汇总了目前已知的情况，并对文献进行批判性分析，以突出尚未解决的问题。
