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

NCT ID: NCT06896708

Last Updated: 2025-12-17

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 766 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-08-12
• Study Completion Date: 2028-03-01

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.

Conditions

Chronic Coronary Syndrome

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

Intensive lipid-lowering strategy

LDL-C reduce to \<1.0mmol/L and by ≥50% relative to baseline levels.

Group Type: EXPERIMENTAL

Intensive lipid-lowering strategy

Intervention Type: DRUG

The initial recommended therapy is 20mg atorvastatin/10mg rosuvastatin plus Ezetimibe or PCSK9i, and the type and dosage of drugs can be adjusted according to the situation. If the target LDL-C level is not achieved during the Follow-up periods, adjustment of drug type and dosage will be carried out according to procedures defined in the protocol.

Standard lipid-lowering strategy

LDL-C reduce to \<1.8mmol/L and by ≥50% relative to baseline levels.

Group Type: ACTIVE_COMPARATOR

Standard lipid-lowering strategy

Intervention Type: DRUG

The initial recommended therapy is 20mg atorvastatin/10mg rosuvastatin, and the type and dosage of drugs can be adjusted according to the situation. If the target L-DLC level is not achieved during the Follow-up periods, adjustment of drug type and dosage will be carried out according to procedures defined in the protocol.

Interventions

Intensive lipid-lowering strategy

The initial recommended therapy is 20mg atorvastatin/10mg rosuvastatin plus Ezetimibe or PCSK9i, and the type and dosage of drugs can be adjusted according to the situation. If the target LDL-C level is not achieved during the Follow-up periods, adjustment of drug type and dosage will be carried out according to procedures defined in the protocol.

Intervention Type: DRUG

Standard lipid-lowering strategy

The initial recommended therapy is 20mg atorvastatin/10mg rosuvastatin, and the type and dosage of drugs can be adjusted according to the situation. If the target L-DLC level is not achieved during the Follow-up periods, adjustment of drug type and dosage will be carried out according to procedures defined in the protocol.

Intervention Type: DRUG

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Liu yong

OTHER

Sponsor Role: lead

Responsible Party

Liu yong

MD

Responsibility Role: SPONSOR_INVESTIGATOR

Locations

The First Affiliated Hospital of Chongqing Medical University

Chongqing, Chongqing Municipality, China

Site Status: NOT_YET_RECRUITING

The Ninth Clinical Medical College of Guangzhou University of Chinese Medicine

Dongguan, Guangdong, China

Site Status: NOT_YET_RECRUITING

The Third Affiliated Hospital of Guangzhou Medical University

Guangzhou, Guangdong, China

Site Status: NOT_YET_RECRUITING

Guangdong Provincial People's Hospital

Guangzhou, Guangdong, China

Site Status: RECRUITING

The Eighth Affiliated Hospital of Sun Yat-sen University

Shenzhen, Guangdong, China

Site Status: NOT_YET_RECRUITING

Zhongshan People's Hospital

Zhongshan, Guangdong, China

Site Status: NOT_YET_RECRUITING

The First Affiliated Hospital of Dalian Medical University

Dalian, Liaoning, China

Site Status: NOT_YET_RECRUITING

Countries

China

Facility Contacts

Yong Liu, MD, PhD

Role: primary

liuyong@gdph.org.cn

+86 2083827812

References

Mendieta G, Pocock S, Mass V, Moreno A, Owen R, Garcia-Lunar I, Lopez-Melgar B, Fuster JJ, Andres V, Perez-Herreras C, Bueno H, Fernandez-Ortiz A, Sanchez-Gonzalez J, Garcia-Alvarez A, Ibanez B, Fuster V. Determinants of Progression and Regression of Subclinical Atherosclerosis Over 6 Years. J Am Coll Cardiol. 2023 Nov 28;82(22):2069-2083. doi: 10.1016/j.jacc.2023.09.814.

Reference Type: RESULT

PMID: 37993199 (View on PubMed)

Vrints C, Andreotti F, Koskinas KC, Rossello X, Adamo M, Ainslie J, Banning AP, Budaj A, Buechel RR, Chiariello GA, Chieffo A, Christodorescu RM, Deaton C, Doenst T, Jones HW, Kunadian V, Mehilli J, Milojevic M, Piek JJ, Pugliese F, Rubboli A, Semb AG, Senior R, Ten Berg JM, Van Belle E, Van Craenenbroeck EM, Vidal-Perez R, Winther S; ESC Scientific Document Group. 2024 ESC Guidelines for the management of chronic coronary syndromes. Eur Heart J. 2024 Sep 29;45(36):3415-3537. doi: 10.1093/eurheartj/ehae177. No abstract available.

Reference Type: RESULT

PMID: 39210710 (View on PubMed)

Raber L, Ueki Y, Otsuka T, Losdat S, Haner JD, Lonborg J, Fahrni G, Iglesias JF, van Geuns RJ, Ondracek AS, Radu Juul Jensen MD, Zanchin C, Stortecky S, Spirk D, Siontis GCM, Saleh L, Matter CM, Daemen J, Mach F, Heg D, Windecker S, Engstrom T, Lang IM, Koskinas KC; PACMAN-AMI collaborators. Effect of Alirocumab Added to High-Intensity Statin Therapy on Coronary Atherosclerosis in Patients With Acute Myocardial Infarction: The PACMAN-AMI Randomized Clinical Trial. JAMA. 2022 May 10;327(18):1771-1781. doi: 10.1001/jama.2022.5218.

Reference Type: RESULT

PMID: 35368058 (View on PubMed)

Mensah GA, Fuster V, Murray CJL, Roth GA; Global Burden of Cardiovascular Diseases and Risks Collaborators. Global Burden of Cardiovascular Diseases and Risks, 1990-2022. J Am Coll Cardiol. 2023 Dec 19;82(25):2350-2473. doi: 10.1016/j.jacc.2023.11.007. No abstract available.

Reference Type: RESULT

PMID: 38092509 (View on PubMed)

Other Identifiers

KY2025-394-02

Identifier Type: -

Identifier Source: org_study_id