The overall objective of the trial is to evaluate the effect of the triple therapy consisting of bempedoic acid (BA), ezetimibe (EZE), and high-intensity atorvastatin or rosuvastatin on changes in coronary plaque burden and plaque morphology in patients with coronary atherosclerosis without significant obstructive coronary artery disease and without prior history of an ischemic vascular event.
The primary objective is to evaluate the effectiveness of the triple therapy in reducing plaque burden. The key secondary objective is to assess the efficacy of the triple therapy by evaluating changes in plaque composition and morphology.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
103
Annualised change in percentage plaque burden (Δ%PB)
This endpoint will evaluate the effectiveness of the triple therapy in reducing plaque burden (PB).
Time frame: Baseline up to 12 months
Key Secondary: Annualised change in normalised non-calcified plaque volume (PV)
This endpoint will assess the efficacy of the triple therapy by evaluating changes in plaque composition and morphology.
Time frame: Baseline up to 12 months
Percentage of participants with regression in normalised total plaque volume (TPV), normalised non-calcified PV, and normalised low attenuation PV at EoT (i.e., ΔPV and Δnon-calcified PV, and Δlow-attenuation PV)
This endpoint will evaluate the potential impact of the triple therapy on total plaque volume (TPV) regression, non-calcified PV regression, and low attenuation PV regression.
Time frame: Baseline up to 12 months
Change in the absolute Agatston coronary artery calcium (CAC) score
This endpoint will evaluate the potential impact of the triple therapy on coronary calcification. CAC measures the total area and density of calcified plaque in the heart's arteries, ranging from 0 to over 400. A score of 0 indicates no plaque, while higher scores indicate increased risk of cardiovascular events, with \>400 indicating extensive disease.
Time frame: Baseline up to 12 months
Annualised ΔTotal Plaque Volume (TPV)
This endpoint will evaluate the effectiveness of the triple therapy in reducing TPV.
Time frame: Baseline up to 12 months
Percentage of participants with regression in TPV (i.e., negative ΔTPV)
This endpoint will assess the proportion of participants exhibiting regression in TPV with triple therapy.
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40 mg dose
Time frame: Baseline up to 12 months
Absolute annualised change in fractional flow reserve derived from computed tomography (FFRCT) of the vessel with the lowest FFR at Baseline
This endpoint will assess changes in non-invasive coronary flow reserve.
Time frame: Baseline up to 12 months
Absolute annualised change in FFRCT of the average of 3 main epicardial coronary arteries (left anterior descending artery [LAD], circumflex artery [Cx], right coronary artery [RCA])
This endpoint will assess changes in non-invasive coronary flow reserve.
Time frame: Baseline up to 12 months
Mean absolute changes in atherosclerosis-related biomarker total cholesterol
This endpoint will evaluate the biochemical impact of triple therapy on critical biomarkers associated with atherosclerosis.
Time frame: Baseline up to 12 months
Mean absolute changes in atherosclerosis-related biomarker low-density lipoprotein cholesterol (LDL-C)
This endpoint will evaluate the biochemical impact of triple therapy on critical biomarkers associated with atherosclerosis.
Time frame: Baseline up to 12 months
Mean absolute changes in atherosclerosis-related biomarker high-density lipoprotein cholesterol (HDL-C)
This endpoint will evaluate the biochemical impact of triple therapy on critical biomarkers associated with atherosclerosis.
Time frame: Baseline up to 12 months
Mean absolute changes in atherosclerosis-related biomarker non-high-density lipoprotein cholesterol (non-HDL-C)
This endpoint will evaluate the biochemical impact of triple therapy on critical biomarkers associated with atherosclerosis.
Time frame: Baseline up to 12 months
Mean absolute changes in atherosclerosis-related biomarkers lipoprotein a (Lp(a)) and apolipoprotein B (apoB)
This endpoint will evaluate the biochemical impact of triple therapy on critical biomarkers associated with atherosclerosis.
Time frame: Baseline up to 12 months
Mean absolute changes in atherosclerosis-related biomarker high-sensitive C reactive protein (hs-CRP)
This endpoint will evaluate the biochemical impact of triple therapy on critical biomarkers associated with atherosclerosis.
Time frame: Baseline up to 12 months
Annualised changes in Framingham steatosis index (FSI) and fibrosis-4 (Fib-4)
This endpoint will assess the potential impact of the triple therapy on measures of liver health.
Time frame: Baseline up to 12 months
Cumulative incidence of adverse events (AEs) under triple therapy during the trial
This endpoint will monitor and assess adverse events (AEs) under triple treatment.
Time frame: Baseline up to 12 months
Rate of treatment discontinuation during the trial
This endpoint will to determine the rate and reasons for treatment discontinuation among trial participants receiving triple therapy.
Time frame: Baseline up to 12 months