Chronic Coronary Syndrome
Conditions
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.
Interventions
DRUGIntensive 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.
DRUGStandard 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.
Sponsors
Liu yong
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The composite events of atherosclerotic plaque progression | 12 months | 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%. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Plaque progression event | 12 months | The proportion of annual change in PAV \>1% |
| 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%) |
| Major adverse cardiac events | 12 months | Composite of nonfatal myocardial infarction, death, or unstable angina driven rehospitalization or revascularization. |
| 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. |
| Change in total atheroma volume by CCTA | 12 months | Evaluating intensive group compared to standard group in total atheroma volume change evaluated by CCTA. |
Countries
China
Outcome results
None listed