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

NCT06821711 | Not Yet Recruiting DMC

• 1 other identifier: KY20242295-F-1
• Study Type: interventional
• Target: 12,000
• Locations: 1 country
• Sites: 1

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

Keywords

Acute coronary syndrome; Chronic coronary syndrome; Percutaneous coronary intervention; LDL-C; lipid

Outcome Measures

Primary Outcomes (1)

• Major Adverse Cardiovascular and Cerebrovascular Events

  MACCE, a composite of cardiovascular death, stroke, myocardial infarction, and any revascularization.

  24 months

Secondary Outcomes (13)

• Patient-oriented composite endpoint

  24 months

• Device-oriented Composite Endpoint

  24 months

• Composite of all-cause death, stroke, and myocardial infarction

  24 months

• All-cause death

  24 months

• Cardiovascular death

  24 months

Other Outcomes (6)

• EuroQol-5D-5L

  24 months

• Everyday Cognition Questionnaire

  24 months

• Pharmacological costs

  24 months

Study Arms (2)

LDL-C target < 0.8 mmol/L

EXPERIMENTAL

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.

Other: Intensive LDL-C control

LDL-C target of 0.8 to 1.4 mmol/L

ACTIVE COMPARATOR

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.

Other: Conventional LDL-C control

Interventions

Intensive LDL-C control 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 < 0.8 mmol/L

Conventional LDL-C control 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

LDL-C target of 0.8 to 1.4 mmol/L

Eligibility Criteria

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

You may qualify if:

• Patients underwent percutaneous coronary intervention due to acute or chronic coronary syndrome
• Patients with ASCVD at extremely high risk
• 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:
• PCI for acute myocardial infarction (AMI, including STEMI or NSTEMI)
• Previous AMI, previous stroke, or previous intervention or surgery for peripheral vascular disease
• Experienced cardiovascular event(s) with LDL-C≤1.8mmol/L
• LDL-C≥4.9mmol/L
• Diabetes
• CKD (eGFR \< 60 ml/min/1.73m2)
• Current smoking
• Recurrent cardio/cerebrovascular events
• History of premature ASCVD (\< 55 male, \< 65 female)
• 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))

You may not qualify if:

• Age less than 18 years;
• Unable to give informed consent or currently participating in other trials;
• 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;
• Concurrent medical condition with a life expectancy of less than 3 years;
• Hemodynamic unstable;
• 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;
• Unable to reach the LDL-C target by known intolerance or contradiction of lipid control medications;
• LDL-C ≤ 1.4 mmol/L at baseline without any lipid control medication lowering LDL-C;
• Known active infection or critical hematologic/endocrine dysfunction.

Sponsors & Collaborators

• Xijing Hospital: lead

Study Sites (1)

Xijing Hospital

Xi'an, Shannxi, 710032, China

Location

MeSH Terms

Conditions

Acute Coronary Syndrome

Condition Hierarchy (Ancestors)

Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases

Study Officials

• Ling Tao, Ph.D., M.D.

  Department of Cardiology, Xijing Hospital

  STUDY CHAIR

• Chao Gao, Ph.D., M.D.

  Department of Cardiology, Xijing Hospital

  STUDY CHAIR

Central Study Contacts

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

CONTACT

86 18629551066; woshigaochao@gmail.com

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: Professor in Cardiology, Director of the Department of Cardiology

Study Record Dates

• First Submitted: February 6, 2025
• First Posted: February 12, 2025
• Study Start: February 20, 2025
• Primary Completion (Estimated): August 15, 2029
• Study Completion (Estimated): August 15, 2029
• Last Updated: February 19, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)