The Prevent Coronary Artery Disease Trial

Inclusion Criteria: * Male or female subjects between 30 to 50 years of age. * No prior history of coronary artery disease, cerebrovascular disease or peripheral artery disease. * Serum LDL-C \> 1.8 mmol/l (70 mg/dl). * Presence of subclinical atherosclerosis as assessed by 3DVUS or by the presence of coronary artery calcium (defined as coronary artery calcium score ≥25), independent of risk calculators; and/or high lifetime risk (≥30%) using the ASCVD calculator; and/or intermediate 10-year risk (≥7.5%) using the ASCVD calculator in the presence of 2 risk enhancers. The presence of atherosclerotic plaque by 3DVUS will be defined according to the PESA study definitions14: plaque is defined as a focal protrusion into the arterial lumen of thickness \>0.5 mm or \>50% if the intima media thickness or intima media thickness \>1.5 mm. CT scan for coronary artery calcium assessment will not be part of the protocol but will be used where available. Risk enhancers are defined as15: * Family history of premature atherosclerotic CVD * Persistently elevated LDL-C ≥ 160 mg/dl * Chronic kidney disease * Metabolic syndrome * Conditions specific to women (e.g. preeclampsia, premature menopause) * Inflammatory diseases (especially rheumatoid arthritis, psoriasis, HIV) * Ethnicity (e.g., South Asian ancestry) * Persistently elevated triglycerides (≥175 mg/dl) * Hs-CRP ≥2 mg/L * Lp(a) levels \>50 mg/dl * apoB ≥130 mg/dl * Ankle-brachial index \<0.9 Exclusion Criteria: 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 subject 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. * Females who are pregnant or nursing, or who are of childbearing potential and unwilling to use at least two methods of highly effective contraception (failure rate less than 1% per year) (e.g. combined oral contraceptives, barrier methods, approved contraceptive implant, long- term injectable contraception, or intrauterine device) for the entire duration of the study. * Severe concomitant non-cardiovascular disease that carries the risk of reducing life expectancy to less than 5 years. * History of malignancy that required surgery (excluding local and wide-local excision), radiation therapy and/or systemic therapy during the three years prior to randomization * Active liver disease defined as any known current infectious, neoplastic, or metabolic pathology of the liver or unexplained elevations in ALT, aspartate aminotransferase (AST), \>3x the ULN, or total bilirubin \>2x ULN at screening confirmed by a repeat abnormal measurement at least 1 week apart. * Known contraindications to anti-lipid therapy * Known history of alcohol and/or drug abuse within the last 5 years. * Treatment with other investigational products or devices within 30 days or five half- lives of the screening visit, whichever is longer. * Planned use of other investigational products or devices during the course of the study. * Any condition that according to the investigator could interfere with the conduct of the study, such as but not limited to: * Subjects who are unable to communicate or to cooperate with the investigator. * Unable to understand the protocol requirements, instructions and study-related restrictions, the nature, scope, and possible consequences of the study (including subjects whose cooperation is doubtful due to drug abuse or alcohol dependency). * Unlikely to comply with the protocol requirements, instructions, and study- related restrictions (e.g., uncooperative attitude, inability to return for follow-up visits, and improbability of completing the study). * Have any medical or surgical condition, which in the opinion of the investigator would put the subject at increased risk from participating in the study. * Persons directly involved in the conduct of the study. * Treatment (within 90 days of screening) with monoclonal antibodies directed towards PCSK9. * History of hypersensitivity to the study treatment or its excipients or to other siRNA drugs.