Intensive Lipid-lowering for Plaque and Major Adverse Cardiovascular Events in Low to Intermediate 10-year ASCVD Risk Population

Not Applicable

• Conditions: Coronary Artery Disease Progression
• Interventions: Drug: Intensive lipid-lowering control; Drug: Moderate-intensity lipid-lowering control

• Registration Number: NCT05462262
• Lead Sponsor: Chinese Academy of Medical Sciences, Fuwai Hospital

Brief Summary

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.

Detailed Description

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).

Study Timeline

• Study First Submitted: 2022-07-07
• Study First Submitted QC: 2022-07-13
• Study First Posted: 2022-07-18
• Study Start: 2022-10-10
• Status Verified: 2024-10
• Last Update Submitted: 2024-10-13
• Last Update Posted: 2024-10-16
• Primary Completion: 2028-12
• Study Completion: 2029-10

Recruitment & Eligibility

• Status: ENROLLING_BY_INVITATION
• Sex: All
• Target Recruitment: 2900

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
intensive lipid-lowering group	Intensive lipid-lowering control	Goal for LDL-C \<1.8 mmol/L or ≥50% reduction from baseline.
moderate-intensity lipid-lowering group	Moderate-intensity lipid-lowering control	Goal for LDL-C \<2.6 mmol/L or 30%-50% reduction from baseline.

Primary Outcome Measures

Name	Time	Method
Major Adverse Cardiovascular Events (MACE)	Within 3 years after the enrollment	Composite of all-cause death, non-fatal MI, non-fatal stroke, any revascularization, and hospitalization for angina

Secondary Outcome Measures

Name	Time	Method
Change in coronary artery calcium score (CACS) on CT	Within 3 years after the enrollment	CACS is a quantification of all coronary calcification by the scoring algorithm proposed by Agatston et al.
Change in coronary total plaque volume(mm³) on CCTA	Within 3 years after the enrollment	Total plaque volume(mm³) is defined as the sum of all plaque volumes for coronary arteries.
Change in coronary plaque burden(%) on CCTA	Within 3 years after the enrollment	Plaque burden(%)=(plaque area/vessel area)×100%
Changes in coronary plaque compositions(mm³, %) on CCTA	Within 3 years after the enrollment	Plaque compositions include lipid(\<30 HU), fibrous(30-150HU), and calcified plaque(\>350HU).
Changes in coronary high-risk plaque characteristics on CCTA	Within 3 years after the enrollment	High-risk plaque characteristics are defined as positive remodeling(remodeling index, \>1.1), low CT attenuation (mean CT number \<30 HU), spotty calcification(punctate calcium within a plaque measuring less than 3 mm in all dimensions), or napkin-ring sign (a ringlike peripheral higher attenuation with central low CT attenuation).

Trial Locations

Locations (1)

Fuwai Hospital; 🇨🇳 Beijing, Beijing, China