VictORION-INCLUSION: Evaluating Inclisiran for Cholesterol Managment in Heart Disease

Inclusion Criteria: Must meet all criteria below.

1. Males and females >= 18 years of age

2. Have clinical ASCVD or ASCVD risk equivalent diagnosis captured in EHR

3. Serum LDL-C ≥ 70 mg/dL for participants with ASCVD, or LDL-C ≥ 100 mg/dL for ASCVDrisk equivalent participants, based on last recorded LDL-C value within thepreceding eighteen (18) months without a subsequent change in lipid loweringtherapy.

4. Willing and able to give informed consent before initiation of any study relatedprocedures and willing to comply with all required study procedures.

5. On statin therapy, or have documented statin intolerance, as determined by thetreating clinician. Participants for whom statin therapy has been recently initiatedmust be on stable therapy for at least 4 weeks and subsequent LDL-C must be abovethe threshold.

6. From historically underrepresented populations in cardiovascular clinical research,including at least one of the following: female sex; Hispanic/Latino ethnicity;Black/African-American, Asian, or Native American race; rural dwelling based on theHRSA definition for determining rural grant eligibility using the Federal Office ofRural Health Policy (FORHP) 2010 County and Census Tract file.

Exclusion Criteria: Cannot meet any criteria below.

1. Planned use of other investigational products or devices during the course of thestudy.

2. Treatment with monoclonal antibodies directed towards PCSK9 within 90 days or withinclisiran within 180 days of pre-screening.

3. History of hypersensitivity to the study treatment or its excipients or to othersiRNA drugs.

4. Pregnant or nursing (lactating) women.

5. Women of child-bearing potential, defined as all women physiologically capable ofbecoming pregnant, unless they are using basic methods of contraception duringdosing of study treatment.

6. New York Heart Association (NYHA) class III or IV heart failure or last known leftventricular ejection fraction <25%.

7. Significant cardiac arrhythmia within 3 months prior to randomization that is notcontrolled by medication or other methods (i.e. via ablation etc.) at the time ofpre-screening. Controlled arrhythmia is not an exclusion.

8. Uncontrolled hypertension: systolic blood pressure >180 mmHg or diastolic bloodpressure >110 mmHg prior to randomization despite antihypertensive therapy.

9. Active liver disease defined as any known current infectious, neoplastic, ormetabolic pathology of the liver or alanine aminotransferase (ALT) elevation >3xULN, aspartate aminotransferase (AST) elevation >3x ULN, or total bilirubinelevation >2x ULN (except participants with Gilbert's syndrome) at pre-screeningconfirmed by a repeat measurement at least one week apart. Lack of repeatmeasurement is not considered an exclusion.

10. End-stage renal disease (ESRD), defined as being on dialysis of any kind.