The Prevent Coronary Artery Disease Trial

Eligibility 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.
• * 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
• * 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.