Optimal LDL-C Target in High-risk Patients After PCI

NCT ID: NCT06821711

Last Updated: 2025-02-19

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: NA
• Total Enrollment: 12000 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-02-20
• Study Completion Date: 2029-08-15

Brief Summary

Extensive evidence from epidemiological, genetic, and randomized controlled trials (RCTs) of lipid-lowering therapies has firmly established a causal relationship between low-density lipoprotein cholesterol (LDL-C) and atherosclerotic cardiovascular disease (ASCVD), establishing LDL-C as both a pathogenic risk factor and a critical therapeutic target.

Lipid-lowering therapies targeting LDL-C have significantly decreased the overall risk in ASCVD patients. Consequently, current guidelines recommend, based on risk stratification, lowering LDL-C levels in high-risk ASCVD patients to <1.4 mmol/L with a ≥50% reduction from baseline. Findings from PROVE IT-TIMI 22, IMPROVE-IT, ODYSSEY OUTCOMES, and FOURIER-OLE trials suggest that achieving extremely low LDL-C levels may further reduce the risk of cardiovascular events in ASCVD patients without substantially increasing clinically relevant adverse events; however, randomized data was still scarce in supporting this notion.

Against these backgrounds, we have designed this trial to investigate whether targeting LDL-C levels <0.8 mmol/L in high-risk ASCVD patients results in a significant reduction in adverse events compared to targeting LDL-C levels of 0.8-1.4 mmol/L.

Conditions

Chronic Coronary Syndrome; Acute Coronary Syndromes; Percutaneous Coronary Intervention; High Risk Patient

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

LDL-C target < 0.8 mmol/L

After randomization, investigators will optimize the intensive lipid-lowering regimen based on the patient's prior medication history, baseline LDL-C level, and target LDL-C level, adjusting and titrating LDL-C levels to achieve the target range.

Group Type: EXPERIMENTAL

Intensive LDL-C control

Intervention Type: OTHER

By Statin, Ezetimibe, or PCSK9i, prescribed according to LDL-C level at baseline and follow-up;

For patients with baseline LDL-C level < 3.0 mmol/L, it is recommended to start lipid control by statin + PCSK9i; for LDL-C level ≥ 3.0 mmol/L, statin + ezetimibe + PCSK9i

LDL-C target of 0.8 to 1.4 mmol/L

After randomization, investigators will optimize the intensive lipid-lowering regimen based on the patient's prior medication history, baseline LDL-C level, and target LDL-C level, adjusting and titrating LDL-C levels to achieve the target range.

Group Type: ACTIVE_COMPARATOR

Conventional LDL-C control

Intervention Type: OTHER

By Statin, Ezetimibe, or PCSK9i, prescribed according to LDL-C level at baseline and follow-up;

For patients with baseline LDL-C level < 3.0 mmol/L, it is recommended to start lipid control by statin alone or statin + ezetimibe; for LDL-C level ≥ 3.0 mmol/L, statin + PCSK9i

Interventions

Intensive LDL-C control

By Statin, Ezetimibe, or PCSK9i, prescribed according to LDL-C level at baseline and follow-up;

For patients with baseline LDL-C level < 3.0 mmol/L, it is recommended to start lipid control by statin + PCSK9i; for LDL-C level ≥ 3.0 mmol/L, statin + ezetimibe + PCSK9i

Intervention Type: OTHER

Conventional LDL-C control

By Statin, Ezetimibe, or PCSK9i, prescribed according to LDL-C level at baseline and follow-up;

For patients with baseline LDL-C level < 3.0 mmol/L, it is recommended to start lipid control by statin alone or statin + ezetimibe; for LDL-C level ≥ 3.0 mmol/L, statin + PCSK9i

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

1. Patients underwent percutaneous coronary intervention due to acute or chronic coronary syndrome

2. Patients with ASCVD at extremely high risk

3. Patients who are able to complete the follow-up and compliant with the allocated treatment

• ASCVD at extremely high risk is defined as fulfilling at least TWO of the following criteria:

1. PCI for acute myocardial infarction (AMI, including STEMI or NSTEMI)

2. Previous AMI, previous stroke, or previous intervention or surgery for peripheral vascular disease

3. Experienced cardiovascular event(s) with LDL-C≤1.8mmol/L

4. LDL-C≥4.9mmol/L

5. Diabetes

6. CKD (eGFR < 60 ml/min/1.73m2)

7. Current smoking

8. Recurrent cardio/cerebrovascular events

9. History of premature ASCVD (< 55 male, < 65 female)

10. Complex PCI (fulfilling at least one of the following criteria: multivessel disease; in-stent restenosis; ≥ 3 stents implanted; total stent length ≥ 60 mm; bifurcation; left main disease; target lesions allocated in bypass graft; chronic total occlusion (≥ 3 months of occlusion))

Exclusion Criteria

1. Age less than 18 years;

2. Unable to give informed consent or currently participating in other trials;

3. Patient who is pregnant or nursing (a pregnancy test must be performed within 7 days prior to randomization in women of child-bearing potential according to local practice), or plans to become pregnant during treatment;

4. Concurrent medical condition with a life expectancy of less than 3 years;

5. Hemodynamic unstable;

6. Active liver disease or hepatic dysfunction (persistent unexplained ALT/AST elevations (≥ 3 × ULN)), patients with a transient increase ALT/AST due to the acute MI may be enrolled;

7. Unable to reach the LDL-C target by known intolerance or contradiction of lipid control medications;

8. LDL-C ≤ 1.4 mmol/L at baseline without any lipid control medication lowering LDL-C;

9. Known active infection or critical hematologic/endocrine dysfunction.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Xijing Hospital

OTHER

Sponsor Role: lead

Responsible Party

Ling Tao, MD, PhD

Professor in Cardiology, Director of the Department of Cardiology

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Ling Tao, Ph.D., M.D.

Role: STUDY_CHAIR

Department of Cardiology, Xijing Hospital

Chao Gao, Ph.D., M.D.

Role: STUDY_CHAIR

Department of Cardiology, Xijing Hospital

Locations

Xijing Hospital

Xi'an, Shannxi, China

Countries

China

Central Contacts

Chao Gao, M.D., Ph.D.

Role: CONTACT

woshigaochao@gmail.com

86 18629551066

Other Identifiers

KY20242295-F-1

Identifier Type: -

Identifier Source: org_study_id