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

Air Force Military Medical University of People's Liberation Army

Status: Not yet enrolling

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

Treatments: Other: Conventional LDL-C control; Other: Intensive LDL-C control

Study type: Interventional

Funder types: Other

Identifiers

NCT06821711

KY20242295-F-1

Details and patient eligibility

About

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.

Enrollment: 12,000 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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12,000 participants in 2 patient groups

LDL-C target < 0.8 mmol/L

Experimental group

Description:

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.

Treatment:

Other: Intensive LDL-C control

LDL-C target of 0.8 to 1.4 mmol/L

Active Comparator group

Description:

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.

Treatment:

Other: Conventional LDL-C control