The goal of this clinical trial is to learn whether an ultra-low LDL-C target (<1.0 mmol/L) can improve clinical outcomes compared with a moderately low LDL-C target (1.0-1.39 mmol/L) in Chinese patients with extreme-high-risk atherosclerotic cardiovascular disease (ASCVD). It also aims to evaluate long-term safety and cost-effectiveness, and explore potential benefit subgroups and underlying mechanisms. The main questions it aims to answer are:

Does an LDL-C target <1.0 mmol/L reduce major adverse cardiovascular events (MACE-4: cardiovascular death, non-fatal myocardial infarction, non-fatal ischemic stroke, urgent coronary revascularization) compared with a target of 1.0-1.39 mmol/L?What are the long-term safety risks including cognitive decline, hemorrhagic stroke, new-onset diabetes, new malignancies and severe adverse drug reactions under different LDL-C targets?Researchers will compare participants receiving an LDL-C target <1.0 mmol/L with those receiving a target of 1.0-1.39 mmol/L to see if the ultra-low LDL-C strategy provides better clinical benefit with acceptable safety and economic value.

Participants will:

Receive lipid-lowering therapy following a mandatory titration-maintenance-off-target correction algorithm according to their assigned LDL-C target Undergo routine follow-up every 3 months, cognitive assessment every 6 months, and comprehensive annual re-examinations for a median of 2 years and up to 5 years Have centralized blinded lipid testing and endpoint adjudication by an independent Clinical Event Committee

Inclusion Criteria:

1. Aged 18-80 years, any sex.
2. Diagnosed with ultra-high-risk ASCVD per 2023 Chinese Lipid Guidelines: either ≥2 major ASCVD events within 24 months, or 1 major ASCVD event plus ≥2 high-risk factors (diabetes, multi-vessel disease, premature CHD family history, elevated Lp(a), hypertension).
3. LDL-C ≥1.0 mmol/L after ≥4-week maximum-tolerated statin plus ezetimibe therapy, confirmed by central laboratory.
4. Able to complete follow-up and examinations; no severe hepatic/renal dysfunction.
5. Voluntary participation with written informed consent.

Exclusion Criteria:

1. Hypersensitivity or intolerance to statins, ezetimibe, or PCSK9 inhibitors.
2. Hemorrhagic stroke, active bleeding, severe trauma or major surgery within 6 months before enrollment.
3. Malignancy (expected survival <3 years), severe liver/kidney disease, or autoimmune disease.
4. Cognitive impairment (MoCA <20) or psychiatric disorders precluding assessment cooperation.
5. Pregnant, breastfeeding, or planning pregnancy during the trial.
6. Participation in other clinical trials or use of other lipid-lowering drugs within 3 months.
7. Poor compliance or other conditions judged by investigators to interfere with the study.