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

Overview

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.

Interventions

• 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.
• 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.

Primary outcome measures

• The composite events of atherosclerotic plaque progression [Time frame: 12 months]

Secondary outcome measures (10)

• Major adverse cardiac events [Time frame: 12 months]
• Plaque progression event [Time frame: 12 months]
• Agatston score changes of coronary artery and aortic valve [Time frame: 12 months]
• Percentage change in total coronary atheroma volume [Time frame: 12 months]
• Change in non-obstructive lesion reversal rate [Time frame: 12 months]
• Change in total atheroma volume by CCTA [Time frame: 12 months]
• Change in total volume and percentage of non-calcified plaques and calcified plaques [Time frame: 12 months]
• Change in the proportion of high-risk plaques [Time frame: 12 months]
• Change in CT Fractional Flow Reserve (CT-FFR) [Time frame: 12 months]
• Change in perivascular fat attenuation index (FAI) [Time frame: 12 months]

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

• Left main coronary artery disease or severe three-vessel disease;
• Ultra-high-risk ASCVD patients: ≥2 severe ASCVD events or 1 severe ASCVD event with ≥2 high-risk factors;
• Use of PCSK9 inhibitors or ezetimibe within 8 weeks prior to study enrollment;
• 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).
• Familial hypercholesterolemia;
• Known allergy/intolerance to lipid-lowering drugs used in the trial;
• Patients with severe congestive heart failure, liver or kidney dysfunction, or malignancy;
• Pregnant or breastfeeding female patients.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Single blind

Primary purpose

Treatment

Study locations

China · 7 centers

• The First Affiliated Hospital of Chongqing Medical University — Chongqing
• The Ninth Clinical Medical College of Guangzhou University of Chinese Medicine — Dongguan
• The Third Affiliated Hospital of Guangzhou Medical University — Guangzhou
• Guangdong Provincial People's Hospital — Guangzhou
• The Eighth Affiliated Hospital of Sun Yat-sen University — Shenzhen
• Zhongshan People's Hospital — Zhongshan
• The First Affiliated Hospital of Dalian Medical University — Dalian

Publications

• 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. PMID 37993199
• 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 mana PMID 39210710
• 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 Ac PMID 35368058
• 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. PMID 38092509

Identifiers

NCT: NCT06896708 · KY2025-394-02

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗