Clinical trial NCT06896708: Effect of Intensive Lipid-Lowering Therapy on Coronary Atherosclerotic Plaque Progression in Young and Middle-Aged Patients With Chronic Coronary Syndrome
Official title: 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
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Chronic Coronary Syndrome
Lead sponsor: Guangdong Provincial People's Hospital
Sponsor class: OTHER
First posted: 2025-03-26
Enrollment: 766
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: The composite events of atherosclerotic plaque progession
timeFrame: 12 months
Secondary outcomes:
measure: Major adverse cardiac events
timeFrame: 12 months
measure: Plaque progession event
timeFrame: 12 months
measure: Agatston score changes of coronary artery and aortic valve
timeFrame: 12 months
measure: Percentage change in total coronary atheroma volume
timeFrame: 12 months
measure: Change in non-obstructive lesion reversal rate
timeFrame: 12 months
measure: Change in total atheroma volume by CCTA
timeFrame: 12 months
measure: Change in total volume and percentage of non-calcified plaques and calcified plaques
timeFrame: 12 months
measure: Change in the proportion of high-risk plaques
timeFrame: 12 months
measure: Change in CT Fractional Flow Reserve (CT-FFR)
timeFrame: 12 months
measure: Change in perivascular fat attenuation index (FAI)
timeFrame: 12 months
Other outcomes:
Locations:
city: Chongqing
country: China
facility: The First Affiliated Hospital of Chongqing Medical University
state: Chongqing
city: Dongguan
country: China
facility: The Ninth Clinical Medical College of Guangzhou University of Chinese Medicine
state: Guangdong
city: Guangzhou
country: China
facility: The Third Affiliated Hospital of Guangzhou Medical University
state: Guangdong
city: Guangzhou
country: China
facility: Guangdong Provincial People's Hospital
state: Guangdong
city: Shenzhen
country: China
facility: The Eighth Affiliated Hospital of Sun Yat-sen University
state: Guangdong
city: Zhongshan
country: China
facility: Zhongshan People's Hospital
state: Guangdong
city: Dalian
country: China
facility: The First Affiliated Hospital of Dalian Medical University
state: Liaoning
Study officials:
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.