The primary objective was to evaluate the effect of PCSK 9 Inhibitor (initiated within 4 h from PCI for the culprit lesion) with high-intensity statin treatment, compared to placebo with high-intensity statin treatment, on cardiovascular events (including cardiovascular death, myocardial infarction, stroke, re-hospitalization due to acute coronary syndromes or heart failure, or any ischemia-driven coronary revascularization) in patients with acute coronary syndrome and multiple lesions. Alirocumab was used before June 10, 2025; Tafolecimab has been used from June 10, 2025 onward.

Patients with acute coronary syndrome (ACS) are at high-risk. ACS patients are commonly associated with multiple lesions or multivessel disease. Percutaneous coronary intervention (PCI) is an effective treatment for culprit lesions in ACS. Statin at high-intensity is recommended by current guidelines in order to prevent/slow the progression of non-culprit disease or restenosis. PCSK9 inhibitor serves as the most powerful medication in lowering LDL via promoting the expression of LDL receptors in the liver. However, if the combination of PCSK9 inhibitor with high-intensity statin treatment could significantly reduce the cardiovascular events in patients with ACS who underwent PCI remains unknown. Alirocumab was used before June 10, 2025; Tafolecimab has been used from June 10, 2025 onward.

Inclusion Criteria:

1. 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.
2. Both male and female subjects aged ≥18 years.
3. 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:

1. 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.
2. 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.
3. 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).

Exclusion Criteria:

1. Fasting serum triglyceride levels exceeding 400 mg/dL (exceeding 4.52 mmol/L) before randomization.
2. Coronary artery disease is located within a saphenous vein graft or an arterial graft.
3. Residual diameter stenosis greater than 50% as determined by visual examination after percutaneous coronary intervention of the culprit lesion.
4. TIMI (Thrombolysis in Myocardial Infarction) flow less than 3 in the culprit vessel after PCI.
5. Unstable clinical status, characterized by hemodynamic (including cardiogenic shock) or electrical instability.
6. Uncontrolled hypertension, indicated by multiple readings with systolic blood pressure (SBP) exceeding 180 mmHg or diastolic blood pressure (DBP) exceeding 110 mmHg.
7. New York Heart Association (NYHA) Class III or IV, and an already known left ventricular ejection fraction (LVEF) below 30%.
8. Known history of hemorrhagic stroke in last 180 days before randomization.
9. 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.
10. Severe renal dysfunction, defined by an estimated glomerular filtration rate (eGFR) below 30 ml/min/1.73m².
11. Active liver disease or hepatic dysfunction.
12. Known intolerance to rosuvastatin or any statin.
13. Known allergy to contrast medium, heparin, aspirin, ticagrelor, prasugrel, or clopidogrel.
14. Subjects who have previously received PCSK9 inhibitors.
15. Subjects who have received cholesterol ester transfer protein inhibitors within the past 12 months before enrollment.
16. Treatment with systemic steroids or systemic cyclosporine within the past 3 months.
17. Known active infection or major hematologic, metabolic, or endocrine dysfunction, as determined by the Investigator.
18. Planned non-cardiac surgery within the next 12 months.
19. Subjects who will not be able to attend the required study visits, as determined by the Investigator.
20. Currently enrolled in another investigational device or drug study.
21. History of cancer within the past 5 years, unless adequately treated basal cell skin cancer, squamous cell skin cancer, or in situ cervical cancer.
22. Estimated life expectancy of less than 12 months.
23. Female of childbearing potential (age <50 years and last menstruation within the last 12 months), who did not undergo tubal ligation, ovariectomy, or hysterectomy.

Neither the participants nor the investigators are aware of the treatment assignment until the end of the trial