Effect of Intensive Lipid-Lowering Therapy on Coronary Atherosclerotic Plaque Progression in Young and Middle-Aged Patients With Chronic Coronary Syndrome

Not Applicable

Not yet recruiting

• Conditions: Chronic Coronary Syndrome
• Interventions: Drug: Intensive lipid-lowering strategy; Drug: Standard lipid-lowering strategy

• Registration Number: NCT06896708
• Lead Sponsor: Liu yong

Brief Summary

This is a multicenter, open-label, parallel-group, randomized trial to determine if intensive lipid-lowering therapy (goal for LDL-C \<1.0 mmol/L and ≥50% reduction frome baseline) could delay progression of coronary atherosclerotic obstructive leisions compared with guideline recommended lipid-lowering therapy (goal for LDL-C \<1.8 mmol/L and ≥50% reduction frome baseline) among participants between 18-60 years old with non-invasively managed chronic coronary syndrome (at least one lesion with a 50%-70% stenosis).

Detailed Description

Coronary artery disease (CAD) remains the leading cause of mortality worldwide, driven predominantly by the intricate dynamics between lipid metabolism and atherosclerosis. In recent years, the incidence of CAD among middle-aged and young patients has been increasing rapidly, with high-risk of recurrent cardiovascular adverse events. Inadequate lipid control is a significant contributing factor to the progession of CAD. 2024 ESC Guidelines for the managementof chronic coronary syndromes (CCS) and 2024 Chinese guidelines for the diagnosis and management of patients with chronic coronary syndrome highlight the importance of moderate-intensity lipid-lowering therapy control for patients with CCS, goal for LDL-C \<1.4 mmol/L or 1.8mmol/L, respectively, and ≥50% reduction frome baseline. The Progression of Early Subclinical Atherosclerosis (PESA) study showed that among individuals with subclinical atherosclerotic plaques, the proportion of plaque regression was highest in young and middle-aged patients, and lower LDL-C levels significantly increased the likelihood of plaque regression. However, for young and middle-aged patients with chronic coronary syndrome, there remains a lack of definitive research data on the effects of intensive lipid-lowering therapy on coronary plaque progession.

CCTA-based noninvasive methods can accurately and sensitively identify and quantify coronary plaque characteristics, providing detailed information about plaque composition, volume, and morphology. This advanced imaging technology allows for precise assessment of high-risk plaque features, such as positive remodeling, low-attenuation plaques, and spotty calcifications, which are critical for evaluating the risk of future adverse cardiovascular events. Additionally, CCTA offers the advantage of longitudinal monitoring, enabling the evaluation of plaque progression or regression in response to lipid-lowering therapy.

This prospective, randomized, open-label, blinded endpoint trial will randomize about 766 participantis aged between 18 and 60 years with with non-invasively managed chronic coronary syndrome (at least one lesion with a 50%-70% stenosis) into the intervention group (goal for LDL-C \<1.0 mmol/ and ≥50% reduction frome baseline) and the control group (goal for LDL-C \<1.8 mmol/L and ≥50% reduction frome baseline). The aim of this study is to assess the role of intensive lipid-lowering control in delaying plaque progression, especially non-calcified plaques identified by CCTA.

Study Timeline

• Study First Submitted: 2025-02-11
• Status Verified: 2025-03
• Study First Submitted QC: 2025-03-24
• Study First Posted: 2025-03-26
• Last Update Submitted: 2025-05-26
• Last Update Posted: 2025-05-28
• Study Start: 2025-06-01
• Primary Completion: 2027-07-01
• Study Completion: 2028-03-01

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 766

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.

2. 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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Intensive lipid-lowering strategy	Intensive lipid-lowering strategy	LDL-C reduce to \<1.0mmol/L and by ≥50% relative to baseline levels.
Standard lipid-lowering strategy	Standard lipid-lowering strategy	LDL-C reduce to \<1.8mmol/L and by ≥50% relative to baseline levels.

Primary Outcome Measures

Name	Time	Method
The composite events of atherosclerotic plaque progession	12 months	A composite end-point comprised of plaque progession, nonfatal myocardial infarction, death, or unstable angina driven rehospitalization or revascularization. Plaque progession is defined as an anual progression of PAV measured by CCTA more than 1%. PAV = (total plaque volume/vessel volume) \*100%.

Secondary Outcome Measures

Name	Time	Method
Plaque progession event	12 months	The proportion of annual change in PAV \>1%
Major adverse cardiac events	12 months	Composite of nonfatal myocardial infarction, death, or unstable angina driven rehospitalization or revascularization.
Agatston score changes of coronary artery and aortic valve	12 months	Evaluating intensive group compared to standard group in Agatston score changes of coronary artery and aortic valve evaluated by CCTA
Percentage change in total coronary atheroma volume	12 months	Evaluating intensive group compared to standard group in total atheroma volume change evaluated by CCTA. PAV = (total plaque volume/vessel volume) \*100%.
Change in non-obstructive lesion reversal rate	12 months	Evaluating intensive group compared to standard group in anual change of rate of improvement from coronary artery obstructive lesions (stenosis rate ≥50%) to non-obstructive lesions (stenosis rate \<50%)
Change in total atheroma volume by CCTA	12 months	Evaluating intensive group compared to standard group in total atheroma volume change evaluated by CCTA.
Change in total volume and percentage of non-calcified plaques and calcified plaques	12 months	Evaluating intensive group compared to standard group in total volume and percentage of non-calcified plaques and calcified plaques' change evaluated by CCTA.
Change in the proportion of high-risk plaques	12 months	Evaluating intensive group compared to standard group in the proportion of high-risk plaques' change evaluated by CCTA.
Change in CT Fractional Flow Reserve (CT-FFR)	12 months	Evaluating intensive group compared to standard group in CT-FFR change evaluated by CCTA.
Change in perivascular fat attenuation index (FAI)	12 months	Evaluating intensive group compared to standard group in FAI change evaluated by CCTA.

Trial Locations

Locations (7)

The First Affiliated Hospital of Chongqing Medical University; 🇨🇳 Chongqing, Chongqing, China

The Ninth Clinical Medical College of Guangzhou University of Chinese Medicine; 🇨🇳 Dongguan, Guangdong, China

The Third Affiliated Hospital of Guangzhou Medical University; 🇨🇳 Guangzhou, Guangdong, China

Guangdong Provincial People's Hospital; 🇨🇳 Guangzhou, Guangdong, China

The Eighth Affiliated Hospital of Sun Yat-sen University; 🇨🇳 Shenzhen, Guangdong, China

Zhongshan People's Hospital; 🇨🇳 Zhongshan, Guangdong, China

The First Affiliated Hospital of Dalian Medical University; 🇨🇳 Dalian, Liaoning, China