Breder Ikaro, Cunha Breder Jessica, Bonilha Isabella, Munhoz Daniel B, Medorima Sheila T Kimura, Oliveira Daniela C, do Carmo Helison R, Moreira Camila, Kontush Anatol, Zimetti Francesca, Zanotti Ilaria, Carvalho Luiz Sergio F, Nadruz Wilson, Muscelli Elza, Quinaglia Thiago, Sposito Andrei C
Atherosclerosis and Vascular Biology Laboratory, Cardiology Department, State University of Campinas, SP, Brazil.
UMR-ICAN 1166, National Institute for Health and Medical Research (INSERM), Sorbonne University, Paris, France.
Ther Adv Chronic Dis. 2020 Sep 28;11:2040622320959248. doi: 10.1177/2040622320959248. eCollection 2020.
Patients with type 2 diabetes mellitus (T2DM) remain at increased cardiovascular residual risk and endothelial dysfunction, even after optimizing metabolic control and treatment by sodium-glucose-2 transporter inhibitors (SGLT2-is). The present study was based on the hypothesis that proprotein convertase subtilisin/kexin 9 inhibitor (PCSK9i) therapy may mitigate endothelial dysfunction in T2DM patients who are on regular treatment by SGLT2-i.
The EXCEED-BHS3 is a prospective, single-center, investigator-blinded, open-label, randomized clinical trial. Participants ( = 110) will be randomized (1:1) to either empagliflozin 25 mg/day alone or empagliflozin 25 mg/day plus evolocumab 140 mg every 2 weeks in addition to optimal medical care. The primary endpoint was defined as the change in the 1-min flow-mediated dilation (FMD) after 16 weeks of treatment. The secondary endpoint is the FMD change after ischemia/reperfusion injury protocol (reserve FMD) after 16 weeks of treatment. Exploratory outcomes comprise the change in FMD and reserve FMD after 8 weeks of treatment and the change after 16 weeks of treatment in the following parameters: plasma levels of nitric oxide, vascular cell adhesion molecule-1 and isoprostane, high-density lipoprotein (HDL) and low-density lipoprotein subfractions profile, HDL function, blood pressure, body mass index, waist circumference and adipokines.
This will be the first study to evaluate the add-on effect of PCSK9i on endothelial function of T2DM patients under regular use of empagliflozin.
ClinicalTrials.gov identifier: NCT03932721.
2型糖尿病（T2DM）患者即使在通过钠-葡萄糖协同转运蛋白2抑制剂（SGLT2-i）优化代谢控制和治疗后，心血管残余风险和内皮功能障碍仍会增加。本研究基于这样的假设：前蛋白转化酶枯草溶菌素/kexin 9抑制剂（PCSK9i）治疗可能减轻接受SGLT2-i常规治疗的T2DM患者的内皮功能障碍。
EXCEED-BHS3是一项前瞻性、单中心、研究者设盲、开放标签、随机临床试验。参与者（n = 110）将被随机（1:1）分为单独使用恩格列净25 mg/天或除最佳医疗护理外，恩格列净25 mg/天加阿利西尤单抗140 mg每2周一次。主要终点定义为治疗16周后1分钟血流介导的血管舒张（FMD）的变化。次要终点是治疗16周后缺血/再灌注损伤方案（储备FMD）后的FMD变化。探索性结果包括治疗8周后FMD和储备FMD的变化以及治疗16周后以下参数的变化：血浆一氧化氮、血管细胞粘附分子-1和异前列腺素水平、高密度脂蛋白（HDL）和低密度脂蛋白亚组分谱、HDL功能、血压、体重指数、腰围和脂肪因子。
这将是第一项评估PCSK9i对常规使用恩格列净的T2DM患者内皮功能附加作用的研究。
ClinicalTrials.gov标识符：NCT03932721。
