A Study of Bempedoic Acid/Ezetimibe/High-intensity Statin in Patients Without Cardiovascular Events

Effects of Bempedoic Acid/Ezetimibe/High-intensity Statin on Plaque Regression and Stabilisation of Coronary Atherosclerosis Among Patients Without Cardiovascular Events

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.

Inclusion Criteria:

In order to be eligible to participate in this trial, a potential participant must meet all of the following criteria:

1. Age ≥18 years

2. Having provided informed consent for participation in this trial

3. Lipid-lowering treatment-naïve

4. Presence of extensive coronary atherosclerosis meeting all of the criteria below:

   • Unequivocal atherosclerosis in ≥5 American Heart Association (AHA) coronary segments (corresponding to a risk equivalent of obstructive coronary artery disease) and coronary artery disease - reporting and data system (CAD-RADS) category 1, 2, or 3
   • Not expected to be a candidate for revascularisation during the duration of the trial
   • Untreated LDL-C ≥2.6 mmol/L and ≤4.5 mmol/L (where a diet without pharmacological treatment is considered 'untreated')

5. Able to provide informed consent

Exclusion Criteria:

A potential participant who meets any of the following criteria will be excluded from participation in this trial:

1. Known or suspected heterozygous or homozygous familial hypercholesterolaemia or familial combined hyperlipidaemia
2. Known contraindication for BA, EZE, atorvastatin, and/or rosuvastatin. A participant with a contraindication for atorvastatin, can be assigned to triple therapy with rosuvastatin, and vice versa.
3. Not expected to remain on a stable dose of high intensity triple therapy for the duration of the trial.
4. History of myocardial infarction, stroke, or peripheral artery disease (PAD), and/or coronary revascularisation (percutaneous coronary intervention [PCI] or coronary artery bypass grafting [CABG])
5. Significant stenosis in the left main artery (≥50%) or proximal LAD artery (≥70%), or 3-vessel coronary artery disease (≥70% stenosis in major branches), clinically indicated for revascularisation
6. Known significant liver disease (e.g., positive hepatitis B or hepatitis C serology) or significant hepatic dysfunction (aspartate aminotransferase [AST] or alanine aminotransferase [ALT] >3 x upper limit of normal [ULN])
7. Known history of gout and/or uric acid levels at Screening ≥6.8 mg/dL
8. Known estimated glomerular filtration rate (eGFR) <40 mL/min/1.73m² and/or receiving dialysis
9. Active malignancy (not including non-melanoma skin cancer)
10. Pregnant or breastfeeding
11. Body mass index (BMI) >35 kg/m²
12. Anticipated life expectancy <52 weeks at the discretion of the local investigator
13. Requiring emergent procedures or having any evidence of ongoing or active clinical instability, including acute chest pain (sudden onset), cardiogenic shock, unstable blood pressure with systolic blood pressure <90 mmHg, severe congestive heart failure (New York Heart Association [NYHA] III or IV), or acute pulmonary oedema
14. Suspicion of acute coronary syndrome (where acute myocardial infarction and unstable angina have not been ruled out)
15. Complex congenital heart disease
16. Known or suspected severe valvular heart disease or valvular heart disease anticipated to require intervention within 52 weeks at the discretion of the local investigator
17. Cardiac arrythmia or tachycardia with significant likelihood of resulting in poor PCD-CTA image quality (especially atrial fibrillation or frequent premature beats)
18. Intracoronary stents
19. Prior pacemaker, internal defibrillator, or abandoned lead implantation
20. Prosthetic heart valves
21. Contraindications to contrast media or other medications needed for proper imaging (e.g., beta blockers and nitroglycerin)
22. Use of any experimental or investigational drug within 40 days or 5 half-lives prior to Screening (whichever is longer), or parallel participation in another interventional study