The POST-ACS Study

Summary

Individuals with T2DM have a two-fold excess risk of cardiovascular (CV) events compared with their non-diabetic counterparts.

Although it is the primary cause of death in T2DM, there is no significant evidence that intensive glucose lowering reduces CV events. Multiple Cardiovascular Outcome Trials have suggested CV safety and benefit with the new class hypoglycemic agents - glucagon-like peptide 1 receptor agonists (GLP-RAs) in patients with DM and a high CV risk profile with a mechanism not directly dependent on their glucose-lowering effect. Varies theories regarding the mechanism of action of GLP-RAs on reducing CV events have been proposed, including reducing inflammation, protection of ischemia/reperfusion injury, and improvement in endothelial dysfunction but the effects of these new agents on in-vivo atherosclerotic plaque burden is currently unproven.

The investigators hypothesize that compared with placebo, 1-year treatment with the oral GLP-RA "Semaglutide" will result in a regression of necrotic core within potentially vulnerable coronary plaques (identified using the novel method "Plaque Maps" analysis on CT Coronary Angiography) in patients with raised HbA1c (\>5.7%) after acute coronary syndromes (ACS).

Methods: One hundred forty patients admitted with ACS and have raised HbA1c \>5.7% will be enrolled in the trial and randomized in a 1:1 blinded fashion to receive conventional therapy and initiation of Semaglutide or conventional therapy plus placebo.

All patients will have a CT Coronary Angiography with Plaque Map analysis of atherosclerotic burden, plaque composition and presence of potentially vulnerable plaque morphology at baseline prior to therapy initiation and following 12 months of treatment. In addition, to help elucidate the potential mechanisms of any anti-atherosclerotic effects, patients will have a non-invasive assessment of vascular function assessed by aortic pulse wave velocity and comprehensive biomarker analysis of inflammation, atherogenesis and oxidative stress.

Conditions

• Diabetes Mellitus
• Acute Coronary Syndrome
• Coronary Artery Disease

Interventions

RADIATION

A computerized tomography (CT) coronary angiogram

Participants in both arms will undergo CT coronary angiogram with Plaque Map analysis at baseline prior to therapy initiation and following 12 months of treatment.

PROCEDURE

Vicorder (Skidmore medical, UK)

Participants in both arms will undergo aortic carotid-femoral pulse wave velocity (cfPWV)through the Vicorder (Skidmore medical, UK), which uses oscillometric cuff-based measurements to establish the index of arterial stiffness. The procedure will be done at baseline and 12 months after therapy initiation.

OTHER

Blood tests for inflammation and oxidative stress markers

All the participants will have (non-fasting) blood samples performed to assess serum glucose, lipid profile and serum biomarkers for plaque initiation (Lipid profile, LpPLA2), endothelial activation (MCP-1), plaque inflammation (hsCRP, IL6, IL18, TNF, advanced glycation end-products), vulnerable transformation (vEGF, PAI-1, BMP-6) and measures of oxidative stress (Ox-LDL, TAOS, TBARs) at baseline, and at 12 months after therapy initiation

Sponsors & Collaborators

• Swansea Bay University Health Board

  lead OTHER

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

TRIPLE

Model

PARALLEL

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2022-08-31

Primary Completion

2024-04-28

Completion

2024-08-01

Countries

• United Kingdom

Study Locations