Current guidelines recommend moderate-intensity lipid-lowering therapy (goal for LDL-C <2.6 mmol/L or 30%-50% reduction from baseline) for patients with intermediate 10-year ASCVD risk. In these patients, early coronary atherosclerotic plaques detected by coronary CT angiography are common, but further interventions are lacking. This study aims to analyze whether intensive lipid-lowering therapy (goal for LDL-C <1.8 mmol/L or ≥50% reduction from baseline) could delay the progression of coronary atherosclerotic lesions and reduce the adverse cardiovascular events in these target patients.

Both American (2019 ACC/AHA Guideline on the Primary Prevention of Cardiovascular Disease) and European (2019 ESC/EAS Guidelines for the management of dyslipidemias) guidelines currently recommended moderate-intensity lipid-lowering (goal for LDL-C <2.6 mmol/L or 30%-50% reduction from baseline) for primary prevention in the population at intermediate (or borderline) 10-year ASCVD risk, but the residual risk in this group of the population remains to be explored, especially in a subset with only nonobstructive atherosclerotic plaques detected by CCTA, for whom further risk stratification and precise interventions for primary prevention are lacking.

CCTA could show accurate images of patients' early coronary atherosclerotic lesions and provides a wealth of image-based anatomical and functional information including plaque burden (total plaque volume, calcification score, segment involvement score, etc.), plaque composition, high-risk plaque characteristics, luminal stenosis, and CT-FFR. With this complete imaging information on CCTA, there is an urgent need to investigate primary prevention strategies and the evidence-based rationale for performing precise risk stratification in low to intermediate-risk populations with nonobstructive coronary atherosclerotic lesions using CCTA.

A prospective, randomized, open-label, blinded endpoint analysis (PROBE) will be conducted in the population at clinical low to intermediate 10-year ASCVD risk with nonobstructive coronary atherosclerotic lesions, predominantly non-calcified plaques detected by CCTA. The purpose of this study is to demonstrate that intensive lipid-lowering could slow down plaque progression and reduce the incidence of MACE in the target population, which provides an evidence-based rationale for further risk re-stratification. Enrolled people will be randomized into the intervention group (goal for LDL-C <1.8 mmol/L or ≥50% reduction from baseline) and the control group (goal for LDL-C <2.6 mmol/L or 30%-50% reduction from baseline).

Inclusion Criteria:

1. Age 40-75 years
2. Low to Intermediate 10-year atherosclerotic cardiovascular disease (ASCVD) risk using pooled cohort equations (PCE).
3. Coronary CT angiography shows atherosclerotic plaque in the main coronary vessels (>2mm diameter) with luminal stenosis <70%

Exclusion Criteria:

1. Combination with serious cardiovascular diseases, including

   1. Heart failure (ejection fraction <30%)
   2. Arrhythmias (persistent atrial flutter/atrial fibrillation, second-degree or third-degree atrioventricular block)
   3. Hemodynamically important valvular disease
   4. Hemodynamically important congenital heart disease
   5. Stroke

2. Myocardial infarction, coronary revascularization, or severe/unstable angina before or within 1 month of screening

3. Active liver disease or hepatic dysfunction (defined as alanine aminotransferase or aspartate aminotransferase> 3 times the upper limit of normal)

4. Unexplained creatine phosphokinase> 6 times the upper limit of normal

5. Nephrotic syndrome

6. Diabetes mellitus

7. Uncontrollable hypertension

8. Uncontrollable hypothyroidism

9. Hypersensitivity to statins

10. Any planned surgical procedure for the treatment of atherosclerosis

11. Gastrointestinal diseases affecting drug absorption or history of gastrointestinal surgery

12. Survival-limiting diseases

13. Concurrent long-term immunosuppressive therapy

14. Participation in another clinical trial concurrently or within 30 days before screening

15. Pregnant or breastfeeding

16. Other unsuitable situations deemed by physicians

blinded endpoint