用他汀类药物降低低密度脂蛋白胆固醇(LDL-C)是减少心血管疾病(CVD)风险的基础治疗手段。可降低LDL-C的非他汀类药物在CVD预防中地位如何?美国动脉硬化、血栓形成与血管生物学(ATVB)委员会近日在《动脉硬化、血栓形成与血管生物学》杂志上发表了一篇关于非他汀类降脂药与心血管风险的降低的声明，回答了上述问题。金宝搏网站登录技巧 小编将其内容摘译要点如下。

        1、声明指出，安慰剂对照随机临床试验已表明，传统非他汀类药物如胆汁酸螯合剂、烟酸和贝特类单一治疗均可降低CVD终点。在这些研究中，患者的LDL-C水平已经被他汀类药物控制良好，添加依折麦布可进一步降低CVD终点，但添加贝特类或烟酸类则无进一步获益。

        2、在新兴的非他汀类药物中，初步证据显示，添加前蛋白转化酶枯草溶菌素9(PCSK9)抑制剂治疗≤78周可减少CVD终点。虽然这些具有前景的早期发现促使欧洲和北美相关机构在近期批准了这些药物上市，但更大型和较为长期预后相关研究仍在进行当中，以提供确定其CVD相关益处的证据。

        3、近期美国批准的其他非他汀类药物包括洛美他派(lomitapide)和载脂蛋白B合成抑制剂米泊美生(Mipomersen)，他们均是通过独特的低密度脂蛋白(LDL)受体独立机制来降低纯合子家族性高胆固醇血症患者的LDL-C水平。

        4、在这份声明中，ATVB委员会还指出了一些未回答的问题，包括检测LDL-C可替代的生化变量，治疗和监测儿童亚临床动脉粥样硬化的证据，以及过度降低LDL-C的潜在风险。

        5、ATVB委员会预计，根据在心血管疾病预防方面积累的获益证据，临床实践将会朝着更为积极地降LDL-C治疗去转变，同时用他汀类药物和非他汀类药物对经过筛选的适宜患者进行更早期的启动治疗。

        参考文献：

        Robert A. Hegele,et al. ATVBAHA.115.306442Published online before print September 16, 2015,doi: 10.1161/ATVBAHA.115.306442

原文

Nonstatin Low-Density Lipoprotein–Lowering Therapy and Cardiovascular Risk Reduction—Statement From ATVB Council

1.       Robert A. Hegele,

2.       Samuel S. Gidding,

3.       Henry N. Ginsberg,

4.       Ruth McPherson,

5.       Frederick J. Raal,

6.       Daniel J. Rader,

7.       Jennifer G. Robinson,

8.       Francine K. Welty

Pharmacological reduction of low-density lipoprotein (LDL) cholesterol using statin drugs is foundational therapy to reduce cardiovascular disease (CVD) risk. Here, we consider the place of nonstatin therapies that also reduce LDL cholesterol in prevention of CVD.

Among conventional nonstatins, placebo-controlled randomized clinical trials showed that bile acid sequestrants, niacin, and fibrates given as monotherapy each reduce CVD end points.From trials in which patients’ LDL cholesterol was already well controlled on a statin, adding ezetimibe incrementally reduced CVD end points,whereas adding a fibrate or niacin showed no incremental benefit.Among emerging nonstatins, monoclonal antibodies against proproteinconvertasesubtilisinkexin type 9 added to a statin and given for ≤78 weeks showed preliminary evidence of reductions in CVD outcomes.Although these promising early findings contributed to the recent approval of these agents in Europe and in North America, much larger and longer duration outcomes studies are ongoing for definitive proof of CVD benefits.Other nonstatin agents recently approved in the United States include lomitapide and mipomersen, which both act via distinctive LDL receptor independent mechanisms to substantially reduce LDL cholesterol in homozygous familial hypercholesterolemia.We also address some unanswered questions, including measuring alternative biochemical variables to LDL cholesterol, evidence for treating children with monitoring of subclinical atherosclerosis, and potential risks of extremely low LDL cholesterol.As evidence for benefit in CVD prevention accumulates, we anticipate that clinical practice will shift toward more assertive LDL-lowering treatment, using both statins and nonstatins initiated earlier in appropriately selected patients.