A Randomized Study to Evaluate the Effect of an "Inclisiran First" Implementation Strategy Compared to Usual Care in Patients With Atherosclerotic Cardiovascular Disease and Elevated LDL-C Despite Receiving Maximally Tolerated Statin Therapy (VICTORION-INITIATE)

Participants eligible for inclusion in this study must meet all of the following criteria:

• Signed informed consent must be obtained prior to participation in the study
• Males and females ≥18 years of age
• History of ASCVD, documented by hospital records, claims data and/or prior laboratory/imaging assessments a Coronary heart disease (CHD):
• Prior myocardial infarction
• Prior coronary revascularization (PCI or CABG)
• Angiographic or CT-imaging (e.g., MDCT/CTA) evidence of coronary atherosclerosis (>70% stenosis in at least one major epicardial coronary artery) b Cerebrovascular disease:
• Prior ischemic stroke confirmed by a brain imaging study, CT or MRI; thought not to be caused by atrial fibrillation, valvular heart disease or mural thrombus
• Carotid artery stenosis >70% on prior angiography or ultrasound
• History of prior percutaneous or surgical carotid artery revascularization c Peripheral arterial disease (PAD):
• Prior documentation of a resting ankle-brachial index ≤0.85
• History of prior percutaneous or surgical revascularization of an iliac, femoral, or popliteal artery or aortic aneurysm
• Prior non-traumatic amputation of a lower extremity due to peripheral artery disease
• Serum LDL-C ≥70 mg/dL or non-HDL-C ≥100 mg/dL
• Fasting triglyceride 30 mL/min by estimated glomerular filtration rate (eGFR) using standardized local clinical methodology
• Participants should be on maximally tolerated statin therapy, as determined by the investigator, with no immediate plans to modify lipid lowering therapies. Statin intolerant patients are eligible if they had documented side effects on at least 2 different statins, including one at the lowest standard dose
• Participants must be willing and able to give informed consent before initiation of any study related procedures and willing to comply with all required study procedures

Exclusion Criteria

Participants meeting any of the following criteria are not eligible for inclusion in this study.

• Any uncontrolled or serious disease, or any medical or surgical condition, that may either interfere with participation in the clinical study, and/or put the participant at significant risk (according to investigator's [or delegate] judgment) if he/she participates in the clinical study
• An underlying known disease, or surgical, physical, or medical condition that, in the opinion of the investigator (or delegate) might interfere with interpretation of the clinical study results
• New York Heart Association (NYHA) class III or IV heart failure or last known left ventricular ejection fraction 180 mmHg or diastolic blood pressure >110 mmHg prior to randomization despite antihypertensive therapy
• Severe concomitant non-cardiovascular disease that carries the risk of reducing life expectancy to less than 2 years
• History of malignancy that required surgery (excluding local and wide-local excision), radiation therapy and/or systemic therapy during the two years prior to randomization
• Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using basic methods of contraception during dosing of investigational drug. Basic contraception methods include:
• Total abstinence (when this is in line with the preferred and usual lifestyle of the participant. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception
• Female sterilization (have had surgical bilateral oophorectomy with or without hysterectomy), total hysterectomy or tubal ligation at least six weeks before taking investigational drug. In case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment
• Male sterilization (at least 6 m prior to screening). For female participants in the study, the vasectomized male partner should be the sole partner for that participant
• Barrier methods o