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

Prior treatment

• 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.
• Not expected to remain on a stable dose of high intensity triple therapy for the duration of the trial.
• Prior pacemaker, internal defibrillator, or abandoned lead implantation
• Contraindications to contrast media or other medications needed for proper imaging (e.g., beta blockers and nitroglycerin)
• 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

Other illness

• History of myocardial infarction, stroke, or peripheral artery disease (PAD), and/or coronary revascularisation (percutaneous coronary intervention \[PCI\] or coronary artery bypass grafting \[CABG\])
• 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
• Active malignancy (not including non-melanoma skin cancer)
• 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
• Suspicion of acute coronary syndrome (where acute myocardial infarction and unstable angina have not been ruled out)
• Complex congenital heart disease
• 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
• Cardiac arrythmia or tachycardia with significant likelihood of resulting in poor PCD-CTA image quality (especially atrial fibrillation or frequent premature beats)
• Prosthetic heart valves

Lab values

• 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 \[ULN\])
• Known history of gout and/or uric acid levels at Screening ≥6.8 mg/dL
• Known estimated glomerular filtration rate (eGFR) \<40 mL/min/1.73m² and/or receiving dialysis

Other

• A potential participant who meets any of the following criteria will be excluded from participation in this trial:
• Known or suspected heterozygous or homozygous familial hypercholesterolaemia or familial combined hyperlipidaemia
• Pregnant or breastfeeding
• Body mass index (BMI) \>35 kg/m²
• Anticipated life expectancy \<52 weeks at the discretion of the local investigator
• Intracoronary stents

• In order to be eligible to participate in this trial, a potential participant must meet all of the following criteria:
• Age ≥18 years
• Having provided informed consent for participation in this trial
• Lipid-lowering treatment-naïve
• 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')
• Able to provide informed consent