PCSK 9 Inhibitor Added to High-Intensity Statin Therapy to Prevent Cardiovascular Events in Patients With ACS After PCI

Prior treatment

• Known history of hemorrhagic stroke in last 180 days before randomization.
• Uncontrolled cardiac arrhythmia, defined as recurrent and symptomatic ventricular tachycardia or atrial fibrillation with rapid ventricular response that has not been controlled by medications in the past 3 months before screening.
• Subjects who have previously received PCSK9 inhibitors.
• Subjects who have received cholesterol ester transfer protein inhibitors within the past 12 months before enrollment.
• Treatment with systemic steroids or systemic cyclosporine within the past 3 months.
• Currently enrolled in another investigational device or drug study.

Other illness

• Coronary artery disease is located within a saphenous vein graft or an arterial graft.
• TIMI (Thrombolysis in Myocardial Infarction) flow less than 3 in the culprit vessel after PCI.
• Uncontrolled hypertension, indicated by multiple readings with systolic blood pressure (SBP) exceeding 180 mmHg or diastolic blood pressure (DBP) exceeding 110 mmHg.
• Active liver disease or hepatic dysfunction.
• Known allergy to contrast medium, heparin, aspirin, ticagrelor, prasugrel, or clopidogrel.
• Known active infection or major hematologic, metabolic, or endocrine dysfunction, as determined by the Investigator.
• Planned non-cardiac surgery within the next 12 months.
• History of cancer within the past 5 years, unless adequately treated basal cell skin cancer, squamous cell skin cancer, or in situ cervical cancer.

Lab values

• Fasting serum triglyceride levels exceeding 400 mg/dL (exceeding 4.52 mmol/L) before randomization.
• New York Heart Association (NYHA) Class III or IV, and an already known left ventricular ejection fraction (LVEF) below 30%.
• Severe renal dysfunction, defined by an estimated glomerular filtration rate (eGFR) below 30 ml/min/1.73m².

Age

• Female of childbearing potential (age \<50 years and last menstruation within the last 12 months), who did not undergo tubal ligation, ovariectomy, or hysterectomy.

Other

• Residual diameter stenosis greater than 50% as determined by visual examination after percutaneous coronary intervention of the culprit lesion.
• Unstable clinical status, characterized by hemodynamic (including cardiogenic shock) or electrical instability.
• Known intolerance to rosuvastatin or any statin.
• Subjects who will not be able to attend the required study visits, as determined by the Investigator.
• Estimated life expectancy of less than 12 months.

• The subject, or their legal guardian, must have a clear understanding of the trial's design and treatment procedures. They must provide written informed consent before any trial-specific tests or procedures are conducted.
• Both male and female subjects aged ≥18 years.
• Subjects who have experienced an ACS and have undergone PCI for culprit lesions (either QFR or FFR \< 0.8) are eligible. ACS is defined as:
  • (1) Unstable angina (characterized by rest pain lasting between 5 and 30 minutes or worsening exertional angina accompanied by either transient ST segment depression or elevation, or angiography revealing visually estimated diameter stenosis of 90% or greater, or a ruptured plaque or thrombotic lesion), or (2) Non-ST elevation myocardial infarction, indicated by positive troponin levels consistent with the clinical syndrome and non-ST segment elevation, or (3) ST elevation myocardial infarction, indicated by positive troponin levels consistent with the clinical syndrome and ST-segment elevation.
  • 4\. Low-density lipoprotein cholesterol levels must meet the following criteria:
• Low-density lipoprotein cholesterol ≥70 mg/dL (≥1.8 mmol/L) in patients who have been on a stable high-intensity statin regimen for at least 4 weeks before enrollment.
• Low-density lipoprotein cholesterol ≥90 mg/dL (≥2.3 mmol/L) in patients who have been on a moderate or low-intensity statin regimen before enrollment.
• Low-density lipoprotein cholesterol ≥125 mg/dL (≥3.2 mmol/L) in patients who are statin-naïve or have not been on a stable statin regimen for at least 4 weeks before enrollment.
  • 5\. Subjects must have at least one culprit lesion for ACS in a major native coronary artery (diameter stenosis \>70% with a QFR or FFR\<0.8), and have at least one non-culprit vessel disease (diameter stenosis ≤70% with a QFR or FFR ≥0.8).