Intensive versus standard cholesterol lowering to slow coronary plaque in young and middle-aged adults with chronic coronary syndrome

Coronary Computed Tomography Study to Assess the Effect of Intensive Lipid-Lowering Therapy on Coronary Atherosclerotic Plaque Progression in Young and Middle-Aged Patients With Chronic Coronary Syndrome: A Nationwide, Multicentre, Randomized Controlled Trial

This trial will test whether more intensive cholesterol lowering (LDL-C <1.0 mmol/L) compared with guideline-level lowering (LDL-C <1.8 mmol/L) can slow or reverse coronary plaque in adults 18–60 with chronic coronary syndrome and a 50–70% lesion on CCTA.

Quick facts

• Phase: Not applicable
• Study type: Interventional
• Enrollment: 766 (estimated)
• Ages: 18 Years to 60 Years
• Sex: All
• Sponsor: Guangdong Provincial People's Hospital (Academic / other)
• Locations: 7 sites (Chongqing, Chongqing Municipality and 6 other locations)
• Trial ID: NCT06896708 on ClinicalTrials.gov

What this trial studies

This is a multicenter, open-label, randomized, parallel-group trial enrolling adults aged 18–60 with chronic coronary syndrome managed without revascularization and at least one 50–70% stenosis identified by coronary CT angiography (CCTA). Participants are randomized to an intensive lipid-lowering strategy targeting LDL-C <1.0 mmol/L and ≥50% reduction from baseline or to a guideline-directed strategy targeting LDL-C <1.8 mmol/L and ≥50% reduction. Coronary plaque volume and characteristics are quantified noninvasively by serial CCTA to compare plaque progression between groups. The trial examines whether deeper LDL-C reduction leads to greater plaque stabilization or regression in this younger patient population.

Who should consider this trial

Good fit: Ideal candidates are adults 18–60 years old with chronic coronary syndrome managed without intervention, at least one CCTA-identified 50–70% coronary lesion, and baseline LDL-C levels meeting the trial's entry criteria (on statin with LDL-C ≥1.8 mmol/L or statin-naive with LDL-C ≥2.6 mmol/L).

Not a fit: Patients with left main or severe three-vessel disease, ultra-high-risk ASCVD, familial hypercholesterolemia, very high baseline LDL-C above the trial cutoffs, recent PCSK9/ezetimibe use, or those who do not meet the CCTA lesion criteria are unlikely to benefit from this protocol.

Why it matters

Potential benefit: If successful, more intensive LDL lowering could slow or reverse coronary plaque progression and may reduce future heart attack risk in younger adults with chronic coronary syndrome.

How similar studies have performed: Previous imaging and outcome studies have shown that lower LDL-C levels are associated with slower plaque progression and more regression, but randomized data specifically testing LDL-C targets below 1.0 mmol/L in young and middle-aged CCS patients are limited.

Eligibility criteria

Inclusion Criteria:

1\. Aged 18-60 years at screening 2. Stable angina symptoms with suspected or confirmed coronary artery disease; 2. CCTA examination demonstrating: at least one major coronary artery with a diameter of ≥1.5mm that has not been intervened and at least one leision with 50%-70% stenosis.

3\. Subjects who have been using statin therapy alone for at least 4 weeks prior to enrollment with a baseline LDL-C ≥1.8mmol/L or subjects who have not initiated lipid-lowering therapy prior to enrollment with a baseline LDL-C≥2.6mmol/L.

Exclusion Criteria:

1. Left main coronary artery disease or severe three-vessel disease;
2. Ultra-high-risk ASCVD patients: ≥2 severe ASCVD events or 1 severe ASCVD event with ≥2 high-risk factors;
3. Use of PCSK9 inhibitors or ezetimibe within 8 weeks prior to study enrollment;
4. The baseline LDL-C was relatively high (LDL-C≥2.6 mmol/L in those taking statins and ≥4.9 mmol/L in those not taking statins).
5. Familial hypercholesterolemia;
6. Known allergy/intolerance to lipid-lowering drugs used in the trial;
7. Patients with severe congestive heart failure, liver or kidney dysfunction, or malignancy;
8. Pregnant or breastfeeding female patients.

Where this trial is running

Chongqing, Chongqing Municipality and 6 other locations

• The First Affiliated Hospital of Chongqing Medical University — Chongqing, Chongqing Municipality, China (Not_yet_recruiting)
• The Ninth Clinical Medical College of Guangzhou University of Chinese Medicine — Dongguan, Guangdong, China (Not_yet_recruiting)
• The Third Affiliated Hospital of Guangzhou Medical University — Guangzhou, Guangdong, China (Not_yet_recruiting)
• Guangdong Provincial People's Hospital — Guangzhou, Guangdong, China (Recruiting)
• The Eighth Affiliated Hospital of Sun Yat-sen University — Shenzhen, Guangdong, China (Not_yet_recruiting)
• Zhongshan People's Hospital — Zhongshan, Guangdong, China (Not_yet_recruiting)
• The First Affiliated Hospital of Dalian Medical University — Dalian, Liaoning, China (Not_yet_recruiting)

Conditions Chronic Coronary Syndrome