Optimal LDL-C Target in High-risk Patients After PCI (REC-SAFETARGET)

Targeting LDL-C to Less Than 0.8 mmol/L in Patients After PCI With High Risk of Cardiovascular Disease: an Open-label, Assessor-blinded, Randomized Trial (REC-SAFETARGET Trial)

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Percutaneous Coronary Intervention; Acute Coronary Syndromes; Chronic Coronary Syndrome; High Risk Patient
• Intervention / Treatment: Other: Intensive LDL-C control; Other: Conventional LDL-C control

• Study Type: Interventional
• Enrollment (Estimated): 12000
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Chao Gao, M.D., Ph.D.; Phone Number: 86 18629551066; Email: woshigaochao@gmail.com

Study Locations

• China
  • Shannxi
    • Xi'an, Shannxi, China, 710032
      • Xijing Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Other: 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
Active Comparator: 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.	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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Major Adverse Cardiovascular and Cerebrovascular Events	MACCE, a composite of cardiovascular death, stroke, myocardial infarction, and any revascularization.	24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Patient-oriented composite endpoint	PoCE, a composite of all-cause death, stroke, myocardial infarction, revascularization, is the first major secondary outcome.	24 months
Device-oriented Composite Endpoint	DoCE, a composite of cardiovascular death, target vessel myocardial infarction, clinically and physiologically-indicated target lesion revascularization, is the second major secondary outcome.	24 months
Composite of all-cause death, stroke, and myocardial infarction	The composite of all-cause death, stroke, and myocardial infarction is the third major secondary outcome.	24 months
All-cause death	All-cause death is considered as other secondary endpoint	24 months
Cardiovascular death	Cardiovascular death is considered as other secondary endpoint	24 months
Myocardial infarction	Myocardial infarction is considered as other secondary endpoint	24 months
Stroke	Stroke is considered as other secondary endpoint	24 months
Ischemic stroke	Ischemic stroke is considered as other secondary endpoint	24 months
Hemorrhagic stroke	Hemorrhagic stroke is considered as other secondary endpoint	24 months
Revascularization	Revascularization is considered as other secondary endpoint	24 months
Target lesion revascularization	Target lesion revascularization is considered as other secondary endpoint	24 months
Clinically and physiologically-indicated target lesion revascularization	Clinically and physiologically-indicated target lesion revascularization is considered as other secondary endpoint	24 months
Cardiovascular hospitalization	Cardiovascular hospitalization is considered as other secondary endpoint	24 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
EuroQol-5D-5L	EuroQol-5D-5L is considered as exploratory endpoint	24 months
Everyday Cognition Questionnaire	Everyday Cognition Questionnaire is considered as exploratory endpoint	24 months
Pharmacological costs	Pharmacological costs is considered as exploratory endpoint	24 months
All adverse events	All adverse events is defined by CTCAE V5.0, considered as safety endpoint	24 months
All serious adverse events	All serious adverse events is defined by CTCAE V5.0, considered as safety endpoint	24 months
Adverse events of interest	Adverse events of interest, including minor bleeding, major bleeding, injection site reactions, allergic reactions, muscle-related adverse events, rhabdomyolysis, cataracts, adjudicated case of new-onset diabetes, neurocognitive disorders, AST/ALT elevation >3 times the upper limit of normal, creatine kinase elevation >5 times the upper limit of normal, which is considered as safety endpoint Adverse events of interest is the safety endpoint.	24 months

Collaborators and Investigators

• Sponsor: Xijing Hospital
• Investigators: Study Chair: 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 record dates

Study Major Dates

• Study Start (Estimated): February 20, 2025
• Primary Completion (Estimated): August 15, 2029
• Study Completion (Estimated): August 15, 2029

Study Registration Dates

• First Submitted: February 6, 2025
• First Submitted That Met QC Criteria: February 6, 2025
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 17, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Keywords: Acute coronary syndrome; Percutaneous coronary intervention; LDL-C; lipid; Chronic coronary syndrome
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Pathologic Processes; Heart Diseases; Disease; Myocardial Ischemia; Syndrome; Acute Coronary Syndrome
• Other Study ID Numbers: KY20242295-F-1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No