Atherosclerotic Cardiovascular Disease (ASCVD)
Conditions
Keywords
Extreme-high-risk ASCVD, LDL-C target, Ultra-low LDL-C, Lipid-lowering therapy
Brief summary
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
Interventions
DRUGLipid-lowering therapy targeting LDL-C <1.0 mmol/L
Statin-ezetimibe-based lipid-lowering therapy with mandatory titration-maintenance-off-target correction algorithm. PCSK9 inhibitor is sequentially added and dose-adjusted based on centralized blinded lipid test results to achieve LDL-C level \<1.0 mmol/L.
DRUGLipid-lowering therapy targeting LDL-C 1.0-1.39 mmol/L
Standard statin-ezetimibe lipid-lowering therapy. Mandatory dose reduction (discontinue ezetimibe → halve statin → discontinue statin) will be performed if LDL-C drops below 1.0 mmol/L, to maintain LDL-C within 1.0-1.39 mmol/L.
Sponsors
Beijing Anzhen Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Major Adverse Cardiovascular Events-4 (MACE-4) | Median 2 years, up to 5 years from randomization | Composite endpoint including cardiovascular death, non-fatal myocardial infarction, non-fatal ischemic stroke, and urgent coronary revascularization. |
Secondary
| Measure | Time frame |
|---|---|
| All-cause mortality | Median 2 years, up to 5 years post-randomization |
| Major Adverse Cardiovascular Events-3 (MACE-3) | Median 2 years, up to 5 years post-randomization |
| individual components of MACE-4 | Median 2 years, up to 5 years post-randomization |
| LDL-C target achievement rate | Median 2 years, up to 5 years post-randomization |
Countries
China
Contacts
CONTACTHai Gao, MD
Outcome results
None listed