Phase 3 study for people with Heart Disease

Reproduced exactly, unedited. Written for researchers rather than for patients.

Inclusion Criteria:

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

At Screening:

1. Signed informed consent must be obtained prior to participation in the study.

2. Males and females, ≥18 years of age at the time of providing written informed consent.

3. Ability to understand study's requirements and provide informed consent and comply with all required study procedures.

4. Hospitalization for a ACS event (STEMI or NSTEMI).

5. Receiving treatment for the qualifying ACS event, according to clinical judgement, by means of medical treatment alone or percutaneous coronary revascularization.

6. Had a successful PCI (with or without stent) for the qualifying event if a PCI was required.

7. LDL-C values measured by the local lab either at the Screening visit or results from local lab tests performed prior to ICF signature, strictly as part of the routine clinical practice in this emergency ACS setting and not older than 2 days of:

   • LDL-C ≥70 mg/dL in participant previously treated with high-intensity statin (atorvastatin ≥40 mg/day or rosuvastatin ≥20 mg/day) or equivalent as per national guidelines and local regulation for at least 4 weeks before screening or
   • LDL-C ≥80 mg/dL in participant previously treated with low/moderate-intensity statin for at least 4 weeks before screening or
   • LDL-C ≥100 mg/dL in participant previously not treated with statins for at least 4 weeks before screening, or who never received statins (including statin intolerant participants).

   At Randomization:

8. The participant must have a Baseline fasting LDL-C ≥70 mg/dL (local lab assessment) to be eligible for randomization.

9. Randomization within 7 days (≤ 7 days) following hospital admission for the qualifying ACS event and before/at discharge.

Exclusion Criteria:

Participant meeting any of the following criteria is not eligible for inclusion in this study.

Only for Japan: For exclusion criteria 6, investigator judgment should be documented in the source data document.

1. Participant who is clinically unstable during hospitalization for the qualifying ACS event, defined by any of the following events within 24 hours prior to randomization:

   • Hemodynamic instability: hypotension, defined as sustained systolic blood pressure of <90 mmHg due to cardiac failure with associated symptoms requiring inotropes
   • Sustained arrhythmic events such as: ventricular storm (e.g., torsade, ventricular tachycardia, ventricular flutter) not resolved before randomization
   • Cardiogenic shock or mechanical complication of myocardial infarction
   • New York Heart Association (NYHA) class IV heart failure
   • Left ventricular ejection fraction <20% at randomization (after all treatment procedures, based on the latest assessment of the LVEF using invasive or non-invasive assessment modalities)
   • Uncontrolled severe hypertension: systolic blood pressure >180 mmHg or diastolic blood pressure >110 mmHg prior to randomization despite antihypertensive therapy.

2. Participant who has undergone or is scheduled to undergo CABG for treatment of the qualifying ACS event.

3. Active liver disease defined as: (i) any known current infectious, neoplastic, or metabolic pathology of the liver or (ii) alanine aminotransferase (ALT) elevation >3x ULN or aspartate aminotransferase (AST) elevation >3x ULN, or total bilirubin elevation >2x ULN (except participant with Gilbert's syndrome) at the Screening visit, in the context of an ACS, and assessed as related to the index event and/or treatment procedures (such as PCI). Eligibility will be based on Investigator's judgement for participant who will be randomized.

4. Renal insufficiency (eGFR <30 mL/min/1.73m2) at the Screening visit.

5. Fasting triglycerides value >400 mg/dL (4.52 mmol/L; assessed by local labs) at randomization visit.

6. Participant, who based on the Investigator's judgement, could reach the LDL-C target value of <55 mg/dL after 4 weeks on statin treatment only.

7. Secondary hypercholesterolemia (based on medical history).

8. Homozygous familial hypercholesterolemia (based on medical history).

9. Participant on apheresis at the Screening visit or for whom an apheresis is planned during study (from Day 1 to EOS).

10. Ongoing or medical history of myopathy at the Screening visit.

11. CK values ≥5x ULN at Screening visit and confirmed by repeat test during Screening (local lab) , in the context of an ACS, and assessed as related to the index event and/or treatment procedures (such as PCI) eligibility will be based on Investigator's judgement for participant who will be randomized (who will be switched to or initiated on the protocol-specified dose of high-intensity statin of atorvastatin ≥40 mg QD or rosuvastatin ≥20 mg QD). Unless a more stringent CK value threshold is mandated by a local regulatory authority (e.g., ≥3x ULN in Korea according to MFDS internal guideline).