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过氧化物酶体增殖物激活受体α调节剂(SPPARMα)模式:概念框架与治疗潜力:国际动脉粥样硬化学会(IAS)和残余风险降低倡议(R3i)基金会的共识声明。

The selective peroxisome proliferator-activated receptor alpha modulator (SPPARMα) paradigm: conceptual framework and therapeutic potential : A consensus statement from the International Atherosclerosis Society (IAS) and the Residual Risk Reduction Initiative (R3i) Foundation.

机构信息

R3i Foundation, Picassoplatz 8, 4010, Basel, Switzerland.

Hospital Israelita Albert Einstein, and Lipid Clinic, Heart Institute (InCor) University of Sao Paulo Medical School Hospital, Sao Paulo, Brazil.

出版信息

Cardiovasc Diabetol. 2019 Jun 4;18(1):71. doi: 10.1186/s12933-019-0864-7.


DOI:10.1186/s12933-019-0864-7
PMID:31164165
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6549355/
Abstract

In the era of precision medicine, treatments that target specific modifiable characteristics of high-risk patients have the potential to lower further the residual risk of atherosclerotic cardiovascular events. Correction of atherogenic dyslipidemia, however, remains a major unmet clinical need. Elevated plasma triglycerides, with or without low levels of high-density lipoprotein cholesterol (HDL-C), offer a key modifiable component of this common dyslipidemia, especially in insulin resistant conditions such as type 2 diabetes mellitus. The development of selective peroxisome proliferator-activated receptor alpha modulators (SPPARMα) offers an approach to address this treatment gap. This Joint Consensus Panel appraised evidence for the first SPPARMα agonist and concluded that this agent represents a novel therapeutic class, distinct from fibrates, based on pharmacological activity, and, importantly, a safe hepatic and renal profile. The ongoing PROMINENT cardiovascular outcomes trial is testing in 10,000 patients with type 2 diabetes mellitus, elevated triglycerides, and low levels of HDL-C whether treatment with this SPPARMα agonist safely reduces residual cardiovascular risk.

摘要

在精准医学时代,针对高危患者特定可改变特征的治疗方法有可能进一步降低动脉粥样硬化性心血管事件的残余风险。然而,纠正动脉粥样硬化性血脂异常仍然是一个主要的未满足的临床需求。血浆甘油三酯升高,无论是否伴有高密度脂蛋白胆固醇(HDL-C)水平降低,都是这种常见血脂异常的一个重要可改变成分,尤其是在 2 型糖尿病等胰岛素抵抗情况下。选择性过氧化物酶体增殖物激活受体α调节剂(SPPARMα)的开发为解决这一治疗空白提供了一种方法。本联合共识专家组评估了首个 SPPARMα 激动剂的证据,并得出结论,该药物基于药理学活性,代表了一种新型治疗类别,与贝特类药物不同,而且重要的是具有安全的肝脏和肾脏特征。正在进行的 PROMINENT 心血管结局试验正在对 10000 名患有 2 型糖尿病、甘油三酯升高和 HDL-C 水平低的患者进行测试,以确定这种 SPPARMα 激动剂是否能安全降低残余心血管风险。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1455/6549355/78d97e0ef911/12933_2019_864_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1455/6549355/e4619acbe15b/12933_2019_864_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1455/6549355/26831de1e362/12933_2019_864_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1455/6549355/d27d5c30f23b/12933_2019_864_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1455/6549355/d1492efa174d/12933_2019_864_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1455/6549355/28d55a09b23f/12933_2019_864_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1455/6549355/aa2d13029017/12933_2019_864_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1455/6549355/78d97e0ef911/12933_2019_864_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1455/6549355/e4619acbe15b/12933_2019_864_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1455/6549355/26831de1e362/12933_2019_864_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1455/6549355/d27d5c30f23b/12933_2019_864_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1455/6549355/d1492efa174d/12933_2019_864_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1455/6549355/28d55a09b23f/12933_2019_864_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1455/6549355/aa2d13029017/12933_2019_864_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1455/6549355/78d97e0ef911/12933_2019_864_Fig7_HTML.jpg

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本文引用的文献

[1]
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Int J Mol Sci. 2019-2-6

[2]
Does nonalcoholic fatty liver disease cause cardiovascular disease? Current knowledge and gaps.

Atherosclerosis. 2019-1-30

[3]
Hypertriglyceridemia in statin-treated US adults: the National Health and Nutrition Examination Survey.

J Clin Lipidol. 2018-12-1

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Low-Grade Inflammation in the Association between Mild-to-Moderate Hypertriglyceridemia and Risk of Acute Pancreatitis: A Study of More Than 115000 Individuals from the General Population.

Clin Chem. 2018-12-5

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J Am Coll Cardiol. 2019-6-25

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Cardiovascular Risk Reduction with Icosapent Ethyl for Hypertriglyceridemia.

N Engl J Med. 2018-11-10

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Alirocumab and Cardiovascular Outcomes after Acute Coronary Syndrome.

N Engl J Med. 2018-11-7

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High Triglycerides Are Associated With Increased Cardiovascular Events, Medical Costs, and Resource Use: A Real-World Administrative Claims Analysis of Statin-Treated Patients With High Residual Cardiovascular Risk.

J Am Heart Assoc. 2018-8-7

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