A Study to Investigate LDL-cholesterol Lowering With Inclisiran Compared to Bempedoic Acid in Patients With Atherosclerotic Cardiovascular Disease.

Prior treatment

• Acute coronary syndrome, ischemic stroke, peripheral arterial revascularization procedure or amputation due to atherosclerotic disease \< 4 months prior to screening visit or V1.
• Participants on more than one other lipid-lowering drug on top of statin at screening visit.
• Previous treatment with a mAb directed towards PCSK9 (e.g., evolocumab, alirocumab) or planned use after screening visit.
• Previous treatment prior to screening with BPA within 90 days
• Previous exposure to Inclisiran or any other non-mAb PCSK9-targeted therapy, either as an investigational or marketed drug.

Other illness

• Planned or expected cardiac, cerebrovascular or peripheral artery surgery or coronary re-vascularization within 6 months after screening visit.
• Heart failure NYHA class IV at screening or V1.

• Fasting LDL-C ≥ 70 mg/dL at screening
• Participants must be on a stable (≥ 4 weeks) and well-tolerated lipid-lowering regimen (with or without Ezetimibe \[10mg\]) that must include a high-intensity statin therapy with either atorvastatin ≥40 mg QD or rosuvastatin ≥20 mg QD in a maximally tolerated or maximally approved dose at screening
• Participants categorized as very high or high CV risk, as defined below:
  • Very high risk participants with at least one of the following:
  • Documented ASCVD: ACS: Unstable angina or myocardial infarction, Stable angina, Coronary revascularization, Unequivocally documented ASCVD upon prior imaging, Stroke and Transient Ischaemic Attack (TIA), Peripheral artery disease (PAD)
  • Diabetes mellitus (DM) with target organ damage (defined as microalbuminuria, retinopathy, or neuropathy), or at least ≥ 3 major risk factors, or early onset of Type 1 DM of long duration (\< 20 years)
  • A calculated SCORE2 ≥ 7.5 % for age \< 50 years; SCORE2 ≥ 10 % for age 50-69 years; SCORE2-OP ≥ 15 % for age ≥ 70 years to estimate 10-year risk of fatal and non-fatal CVD
  • Pre-existing diagnosis of heterozygous familial hyper-cholesterolemia (HeFH) with ASCVD or with another major risk factor OR
  • High risk participants with at least one of the following:
  • Markedly elevated single risk factors, in particular total cholesterol \> 310 mg/dL, LDL-C \> 190 mg/dL, or blood pressure ≥ 180/110 mmHg
  • Pre-existing diagnosis of HeFH without other major risk factors
  • DM without target organ damage (defined as microalbuminuria, retinopathy, or neuropathy), with DM duration ≥ 10 years or other additional risk factor
  • Moderate chronic kidney disease (eGFR 30-59 mL/min/1.73m2)
  • A calculated SCORE2 2.5 to \< 7.5 % for age \< 50 years; SCORE2 5 to \< 10 % for age 50-69 years; SCORE2-OP 7.5 to \< 15 % for age ≥ 70 years to estimate 10-year risk of fatal and non-fatal CVD as defined by the cardiovascular risk categories in the 2019 ESC/EAS guideline (Mach et al 2020), and updated SCORE2 and SCORE2-OP (Hageman et al 2021, de Vries et al 2021, Visseren et al 2021). Further details for documented ASCVD will be provided in the protocol.
• Fasting triglyceride \< 400 mg/dL at screening