Rationale and design of the expanded combination of evolocumab plus empagliflozin in diabetes: EXCEED-BHS3 trial

• Main Authors: Ikaro Breder (Author), Jessica Cunha Breder (Author), Isabella Bonilha (Author), Daniel B. Munhoz (Author), Sheila T. Kimura Medorima (Author), Daniela C. Oliveira (Author), Helison R. do Carmo (Author), Camila Moreira (Author), Anatol Kontush (Author), Francesca Zimetti (Author), Ilaria Zanotti (Author), Luiz Sergio F. Carvalho (Author), Wilson Nadruz (Author), Elza Muscelli (Author), Thiago Quinaglia (Author), Andrei C. Sposito (Author)
• Format: Book
• Published: SAGE Publishing, 2020-09-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.

Summary

Background: 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. Methods: The EXCEED-BHS3 is a prospective, single-center, investigator-blinded, open-label, randomized clinical trial. Participants ( n  = 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. Conclusion: 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. Trial registration: ClinicalTrials.gov identifier: NCT03932721

Item Description

2040-6231
10.1177/2040622320959248