Target-Oriented Strategy of Ultra-Low LDL-C (<1.0 vs. 1.0-1.39 mmol/L) in Extreme-High-Risk ASCVD Patients: Clinical Benefit, Safety and Cost-Effectiveness Assessment

NCT07615296 | Not Yet Recruiting

• 1 other identifier: LIPID-2026-001
• Study Type: interventional
• Target: 6,000
• Locations: 1 country
• Sites: 1

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

Conditions

Atherosclerotic Cardiovascular Disease (ASCVD)

Keywords

Extreme-high-risk ASCVD, LDL-C target, Ultra-low LDL-C, Lipid-lowering therapy

Outcome Measures

Primary Outcomes (1)

• Major Adverse Cardiovascular Events-4 (MACE-4)

  Composite endpoint including cardiovascular death, non-fatal myocardial infarction, non-fatal ischemic stroke, and urgent coronary revascularization.

  Median 2 years, up to 5 years from randomization

Secondary Outcomes (4)

• 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

Study Arms (2)

Ultra-low LDL-C target group

EXPERIMENTAL

Participants receive statin-ezetimibe-based lipid-lowering therapy with mandatory titration algorithm, adding PCSK9 inhibitor sequentially to achieve LDL-C \<1.0 mmol/L.

Drug: Lipid-lowering therapy targeting LDL-C <1.0 mmol/L

Moderate-low LDL-C target group

ACTIVE COMPARATOR

Participants maintain statin-ezetimibe therapy; dose reduction is enforced if LDL-C \<1.0 mmol/L to keep level within 1.0-1.39 mmol/L.

Drug: Lipid-lowering therapy targeting LDL-C 1.0-1.39 mmol/L

Interventions

Lipid-lowering therapy targeting LDL-C 1.0-1.39 mmol/L DRUG

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.

Moderate-low LDL-C target group

Lipid-lowering therapy targeting LDL-C <1.0 mmol/L DRUG

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.

Ultra-low LDL-C target group

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Aged 18-80 years, any sex.
• 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).
• LDL-C ≥1.0 mmol/L after ≥4-week maximum-tolerated statin plus ezetimibe therapy, confirmed by central laboratory.
• Able to complete follow-up and examinations; no severe hepatic/renal dysfunction.
• Voluntary participation with written informed consent.

You may not qualify if:

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

Sponsors & Collaborators

• Beijing Anzhen Hospital: lead

Study Sites (1)

Beijing Anzhen Hospital, Capital Medical University

Beijing, Beijing Municipality, 100029, China

Location

MeSH Terms

Conditions

Atherosclerosis

Condition Hierarchy (Ancestors)

Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Cardiovascular Diseases

Central Study Contacts

Hai Gao, MD

CONTACT

+86 13901015971; gaohai1221@mail.ccmu.edu.cn

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chief Physician

Study Record Dates

• First Submitted: May 23, 2026
• First Posted: May 29, 2026
• Study Start (Estimated): January 1, 2027
• Primary Completion (Estimated): December 31, 2029
• Study Completion (Estimated): December 31, 2031
• Last Updated: May 29, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)