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依洛尤单抗联合恩格列净改善糖尿病患者的内皮功能:一项随机、活性对照试验。

Evolocumab on top of empagliflozin improves endothelial function of individuals with diabetes: randomized active-controlled trial.

机构信息

Division of Cardiology, State University of Campinas (Unicamp), Campinas, Sao Paulo, 13084-971, Brazil.

Brazilian Heart Study Group, State University of Campinas (Unicamp), Campinas, Sao Paulo, 13084-971, Brazil.

出版信息

Cardiovasc Diabetol. 2022 Aug 6;21(1):147. doi: 10.1186/s12933-022-01584-8.

DOI:10.1186/s12933-022-01584-8
PMID:35933413
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9356512/
Abstract

BACKGROUND

Sodium-glucose cotransporter 2 inhibitors (SGLT2i) improve endothelial dysfunction and reduce cardiovascular events in individuals with type 2 diabetes (T2D). Proprotein convertase subtilisin/kexin 9 (PCSK9i) inhibitors reduce cardiovascular events in high-risk patients. Whether the addition of PCSK9i to SGLT2i treatment adds benefits is not known.

OBJECTIVES

To assess the PCSK9-i effect on the endothelial function of T2D individuals under treatment with SGLT2-i.

METHODS

Individuals with T2D were randomized in a 1:1 ratio to a 16-week treatment with either empagliflozin (E) or empagliflozin plus evolocumab (EE). The primary endpoint was post-treatment change from baseline in flow-mediated dilation (FMD) at 1-min. Secondary outcomes included changes in plasma levels of nitric oxide metabolites and isoprostane.

RESULTS

A total of 110 patients were enrolled, the mean age was 58 years, and 71% were men. The median post-treatment change in FMD at 1-min was 2.7% (interquartile range [IQR]: 0.9%) and 0.4% (IQR: 0.9%) in the EE and E groups, respectively (p < 0.001). There was a greater increase in plasma levels of nitrate [5.9 (16.5) vs. 2.6 (11.8); p = 0.001] and nitrite [0.14 (0.72) vs. 0.02 (0.74); p = 0.025] in the EE group than in the E group, respectively. Isoprostane reduction was more pronounced in the EE group when compared to the E group [-1.7 (5.9) vs. -1.1 (5.3); p < 0.001).

CONCLUSIONS

In individuals with T2D, the addition of evolocumab on top of empagliflozin improves endothelial function.

摘要

背景

钠-葡萄糖共转运蛋白 2 抑制剂(SGLT2i)可改善 2 型糖尿病(T2D)患者的内皮功能障碍并降低心血管事件发生率。前蛋白转化酶枯草溶菌素 9(PCSK9i)抑制剂可降低高危患者的心血管事件发生率。但目前尚不清楚在 SGLT2i 治疗的基础上添加 PCSK9i 是否会带来额外获益。

目的

评估 PCSK9i 对接受 SGLT2i 治疗的 T2D 患者内皮功能的影响。

方法

将 T2D 患者按照 1:1 的比例随机分为 16 周的恩格列净(E)组或恩格列净联合依洛尤单抗(EE)组。主要终点为治疗 1 分钟后血流介导的舒张(FMD)较基线的变化。次要终点包括血浆一氧化氮代谢物和异前列烷水平的变化。

结果

共纳入 110 例患者,平均年龄为 58 岁,71%为男性。治疗 1 分钟后 FMD 的中位变化值分别为 EE 组 2.7%(四分位距 [IQR]:0.9%)和 E 组 0.4%(IQR:0.9%)(p<0.001)。EE 组血浆硝酸盐水平升高更为明显[5.9(16.5)比 2.6(11.8);p=0.001],亚硝酸盐水平升高更为明显[0.14(0.72)比 0.02(0.74);p=0.025]。与 E 组相比,EE 组的异前列烷降低更为明显[-1.7(5.9)比-1.1(5.3);p<0.001]。

结论

在 T2D 患者中,在恩格列净的基础上加用依洛尤单抗可改善内皮功能。

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本文引用的文献

1
Targeting inflammation in atherosclerosis - from experimental insights to the clinic.靶向动脉粥样硬化炎症——从实验研究到临床实践。
Nat Rev Drug Discov. 2021 Aug;20(8):589-610. doi: 10.1038/s41573-021-00198-1. Epub 2021 May 11.
2
Effects of evolocumab in individuals with type 2 diabetes with and without atherogenic dyslipidemia: An analysis from BANTING and BERSON.依洛尤单抗对伴或不伴致动脉粥样硬化性血脂异常的 2 型糖尿病患者的影响:来自 BANTING 和 BERSON 的分析。
Cardiovasc Diabetol. 2021 Apr 30;20(1):94. doi: 10.1186/s12933-021-01287-6.
3
Brazilian Guidelines of Hypertension - 2020.
糖尿病中PCSK9表达的增加促进VEGFR2泛素化,从而抑制内皮功能和皮肤伤口愈合。
Sci China Life Sci. 2024 Dec;67(12):2635-2649. doi: 10.1007/s11427-023-2688-8. Epub 2024 Aug 15.
4
The role of PCSK9 in heart failure and other cardiovascular diseases-mechanisms of action beyond its effect on LDL cholesterol.载脂蛋白 C-III 在心力衰竭和其他心血管疾病中的作用:除了对 LDL 胆固醇的影响之外的作用机制。
Heart Fail Rev. 2024 Sep;29(5):917-937. doi: 10.1007/s10741-024-10409-7. Epub 2024 Jun 18.
5
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Int J Mol Sci. 2024 Apr 8;25(7):4108. doi: 10.3390/ijms25074108.
6
The effect of sodium-glucose co-transporter-2 inhibitors on markers of subclinical atherosclerosis.钠-葡萄糖共转运蛋白 2 抑制剂对亚临床动脉粥样硬化标志物的影响。
Ann Med. 2023;55(2):2304667. doi: 10.1080/07853890.2024.2304667. Epub 2024 Jan 17.
7
The translational potential of miR-26 in atherosclerosis and development of agents for its target genes ACC1/2, COL1A1, CPT1A, FBP1, DGAT2, and SMAD7.miR-26 在动脉粥样硬化中的转译潜力及其靶基因 ACC1/2、COL1A1、CPT1A、FBP1、DGAT2 和 SMAD7 相关药物的研发。
Cardiovasc Diabetol. 2024 Jan 9;23(1):21. doi: 10.1186/s12933-024-02119-z.
8
The Anti-Thrombotic Effects of PCSK9 Inhibitors.前蛋白转化酶枯草溶菌素9(PCSK9)抑制剂的抗血栓形成作用。
Pharmaceuticals (Basel). 2023 Aug 22;16(9):1197. doi: 10.3390/ph16091197.
9
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Cardiovasc Diabetol. 2023 May 20;22(1):119. doi: 10.1186/s12933-023-01856-x.
《巴西高血压指南 - 2020》
Arq Bras Cardiol. 2021 Mar;116(3):516-658. doi: 10.36660/abc.20201238.
4
Real-world data on metabolic effects of PCSK9 inhibitors in a tertiary care center in patients with and without diabetes mellitus.真实世界数据:在有或没有糖尿病的患者中,三级护理中心的 PCSK9 抑制剂对代谢的影响。
Cardiovasc Diabetol. 2021 Apr 24;20(1):89. doi: 10.1186/s12933-021-01283-w.
5
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Cardiovasc Diabetol. 2021 Mar 26;20(1):74. doi: 10.1186/s12933-021-01264-z.
6
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Neurologia (Engl Ed). 2022 Mar;37(2):136-150. doi: 10.1016/j.nrl.2020.11.006. Epub 2021 Jan 6.
7
PCSK9 and atherosclerosis: Looking beyond LDL regulation.PCSK9 与动脉粥样硬化:超越 LDL 调控的视角。
Eur J Clin Invest. 2021 Apr;51(4):e13459. doi: 10.1111/eci.13459. Epub 2020 Dec 3.
8
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J Am Heart Assoc. 2020 Jul 21;9(14):e016263. doi: 10.1161/JAHA.120.016263. Epub 2020 Jul 17.
10
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Nutr Metab Cardiovasc Dis. 2020 Jun 9;30(6):996-1004. doi: 10.1016/j.numecd.2020.02.018. Epub 2020 Mar 6.