Evaluation of efficacy and safety of early in hospital initiation of inclisiran treatment in patients with acute coronary syndromes

Other illness

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

Lab values

• 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 • Arrhythmic events: Ventricular storm (e.g., torsade, ventricular tachycardia, ventricular flutter) • 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.
• 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).
• Active liver disease defined as: (i) any known current infectious, neoplastic, or metabolic pathology of the liver or (ii) ALT elevation >3x ULN, or 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.
• Renal insufficiency (eGFR <30 mL/min/1.73m2) at the Screening visit.
• Fasting triglycerides value >400 mg/dL (4.52 mmol/L; assessed by local labs) at randomization visit.
• 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.

Other

• Participant who has undergone or is scheduled to undergo CABG for treatment of the qualifying ACS event.
• Secondary hypercholesterolemia (based on medical history).
• Homozygous familial hypercholesterolemia (based on medical history).
• Participant on apheresis at Screening visit.

• Signed informed consent must be obtained prior to participation in the study.
• Males and females, ≥18 years of age at the time of providing written informed consent.
• Ability to understand the study's requirements and provide informed consent and comply with all required study procedures.
• Hospitalization for an ACS event (STEMI or NSTEMI).
• Receiving treatment for the qualifying ACS event, according to clinical judgement, by means of medical treatment alone or percutaneous coronary revascularization.
• Had a successful PCI (with or without stent) for the qualifying event, if PCI is required.
• LDL-C value at the Screening visit measured by the local lab 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 ≥100 mg/dL in participant previously treated with low/moderate-intensity statin for at least 4 weeks before screening or • LDL-C ≥125 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).
• The participant must have a Baseline fasting LDL-C ≥70 mg/dL (local lab assessment) to be eligible for randomization.
• Randomization within 7 days (≤ 7 days) following hospital admission for the qualifying ACS event and before/at discharge.