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

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 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).

Study Overview

• Status: Recruiting
• Conditions: Chronic Coronary Syndrome
• Intervention / Treatment: Drug: Intensive lipid-lowering strategy; Drug: Standard lipid-lowering strategy

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 Type: Interventional
• Enrollment (Estimated): 766
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Chongqing Municipality
    • Chongqing, Chongqing Municipality, China, 400015
      • Not yet recruiting
      • The First Affiliated Hospital of Chongqing Medical University
  • Guangdong
    • Dongguan, Guangdong, China, 523000
      • Not yet recruiting
      • The Ninth Clinical Medical College of Guangzhou University of Chinese Medicine
    • Guangzhou, Guangdong, China, 510100
      • Recruiting
      • Guangdong Provincial People's Hospital
      • Contact: Yong Liu, MD, PhD; Phone Number: +86 2083827812; Email: liuyong@gdph.org.cn
    • Guangzhou, Guangdong, China, 510000
      • Not yet recruiting
      • The Third Affiliated Hospital of Guangzhou Medical University
    • Shenzhen, Guangdong, China, 518033
      • Not yet recruiting
      • The Eighth Affiliated Hospital of Sun Yat-Sen University
    • Zhongshan, Guangdong, China, 528400
      • Not yet recruiting
      • Zhongshan People's Hospital
  • Liaoning
    • Dalian, Liaoning, China, 116000
      • Not yet recruiting
      • The First Affiliated Hospital of Dalian Medical University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intensive lipid-lowering strategy; LDL-C reduce to <1.0mmol/L and by ≥50% relative to baseline levels.	Drug: 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.
Active Comparator: Standard lipid-lowering strategy; LDL-C reduce to <1.8mmol/L and by ≥50% relative to baseline levels.	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.

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Liu yong

Publications and helpful links

General Publications

• 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.
• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): August 12, 2025
• Primary Completion (Estimated): July 1, 2027
• Study Completion (Estimated): March 1, 2028

Study Registration Dates

• First Submitted: February 11, 2025
• First Submitted That Met QC Criteria: March 24, 2025
• First Posted (Actual): March 26, 2025

Study Record Updates

• Last Update Posted (Actual): December 17, 2025
• Last Update Submitted That Met QC Criteria: December 9, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Pathological Conditions, Anatomical; Disease; Syndrome; Plaque, Atherosclerotic
• Other Study ID Numbers: KY2025-394-02

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No