Clinical trial NCT06821711: Optimal LDL-C Target in High-risk Patients After PCI
Official title: 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)
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
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
Lead sponsor: Xijing Hospital
Sponsor class: OTHER
First posted: 2025-02-12
Enrollment: 12000
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Major Adverse Cardiovascular and Cerebrovascular Events
timeFrame: 24 months
Secondary outcomes:
measure: Patient-oriented composite endpoint
timeFrame: 24 months
measure: Device-oriented Composite Endpoint
timeFrame: 24 months
measure: Composite of all-cause death, stroke, and myocardial infarction
timeFrame: 24 months
measure: All-cause death
timeFrame: 24 months
measure: Cardiovascular death
timeFrame: 24 months
measure: Myocardial infarction
timeFrame: 24 months
measure: Stroke
timeFrame: 24 months
measure: Ischemic stroke
timeFrame: 24 months
measure: Hemorrhagic stroke
timeFrame: 24 months
measure: Revascularization
timeFrame: 24 months
measure: Target lesion revascularization
timeFrame: 24 months
measure: Clinically and physiologically-indicated target lesion revascularization
timeFrame: 24 months
measure: Cardiovascular hospitalization
timeFrame: 24 months
Other outcomes:
measure: EuroQol-5D-5L
timeFrame: 24 months
measure: Everyday Cognition Questionnaire
timeFrame: 24 months
measure: Pharmacological costs
timeFrame: 24 months
measure: All adverse events
timeFrame: 24 months
measure: All serious adverse events
timeFrame: 24 months
measure: Adverse events of interest
timeFrame: 24 months
Locations:
city: Xi'an
country: China
facility: Xijing Hospital
state: Shannxi
Study officials:
affiliation: Department of Cardiology, Xijing Hospital
name: Ling Tao, Ph.D., M.D.
role: STUDY_CHAIR
affiliation: Department of Cardiology, Xijing Hospital
name: Chao Gao, Ph.D., M.D.
role: STUDY_CHAIR
References: