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

Coronary Artery Disease Progression Clinical Trial

— ILLUMINATION  

Official title:

Effects of Intensive Lipid-lowering on Coronary Atherosclerotic Plaque Phenotype and Major Adverse Cardiovascular Events in Adults With Low to Intermediate 10-year ASCVD Risk: a Prospective, Randomized, Open-label, Blinded Endpoint Analysis(PROBE)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05462262
• Other study ID #: 2021-CXGC03-3
• Status: Recruiting
• Phase: N/A
• Start date: October 10, 2022
• Est. completion date: December 2025

Study information

• Verified date: April 2023
• Source: Chinese Academy of Medical Sciences, Fuwai Hospital
• Contact: Bin Lu, MD
• Phone: 13911285857
• Email: blu[@]vip.sina.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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 (luminal stenosis<50%) 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.

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(luminal stenosis<50%) 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. And 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 control group (goal for LDL-C <2.6 mmol/L or 30%-50% reduction from baseline).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 2900
• Est. completion date: December 2025
• Est. primary completion date: December 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years to 75 Years

Eligibility

Inclusion Criteria:

1. Age 40-75 years

2. Low to Intermediate 10-year atherosclerotic cardiovascular disease (ASCVD) risk by using pooled cohort equations (PCE).

3. Coronary CT angiography shows atherosclerotic plaque in the main coronary vessels (>2mm diameter) with luminal stenosis <50%

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

Related Conditions & MeSH terms

• Coronary Artery Disease
• Coronary Artery Disease Progression
• Disease Progression

Intervention

Drug:
• Intensive lipid-lowering control
The initial recommended therapy is 10-20mg atorvastatin plus Ezetimibe, and the type and dosage of drugs can be adjusted according to the situation.
• Moderate-intensity lipid-lowering control
The initial recommended therapy is 10-20mg atorvastatin, and the type and dosage of drugs can be adjusted according to the situation.

Locations

Country	Name	City	State
China	Fuwai Hospital	Beijing	Beijing

Sponsors (1)

Lead Sponsor	Collaborator
Chinese Academy of Medical Sciences, Fuwai Hospital

Country where clinical trial is conducted

China, 

References & Publications (3)

Arnett DK, Blumenthal RS, Albert MA, Buroker AB, Goldberger ZD, Hahn EJ, Himmelfarb CD, Khera A, Lloyd-Jones D, McEvoy JW, Michos ED, Miedema MD, Munoz D, Smith SC Jr, Virani SS, Williams KA Sr, Yeboah J, Ziaeian B. 2019 ACC/AHA Guideline on the Primary Prevention of Cardiovascular Disease: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation. 2019 Sep 10;140(11):e596-e646. doi: 10.1161/CIR.0000000000000678. Epub 2019 Mar 17. No abstract available. Erratum In: Circulation. 2019 Sep 10;140(11):e649-e650. Circulation. 2020 Jan 28;141(4):e60. Circulation. 2020 Apr 21;141(16):e774. — View Citation

Grundy SM, Stone NJ, Bailey AL, Beam C, Birtcher KK, Blumenthal RS, Braun LT, de Ferranti S, Faiella-Tommasino J, Forman DE, Goldberg R, Heidenreich PA, Hlatky MA, Jones DW, Lloyd-Jones D, Lopez-Pajares N, Ndumele CE, Orringer CE, Peralta CA, Saseen JJ, Smith SC Jr, Sperling L, Virani SS, Yeboah J. 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA Guideline on the Management of Blood Cholesterol: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation. 2019 Jun 18;139(25):e1082-e1143. doi: 10.1161/CIR.0000000000000625. Epub 2018 Nov 10. Erratum In: Circulation. 2019 Jun 18;139(25):e1182-e1186. — View Citation

Mach F, Baigent C, Catapano AL, Koskinas KC, Casula M, Badimon L, Chapman MJ, De Backer GG, Delgado V, Ference BA, Graham IM, Halliday A, Landmesser U, Mihaylova B, Pedersen TR, Riccardi G, Richter DJ, Sabatine MS, Taskinen MR, Tokgozoglu L, Wiklund O; ESC Scientific Document Group. 2019 ESC/EAS Guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk. Eur Heart J. 2020 Jan 1;41(1):111-188. doi: 10.1093/eurheartj/ehz455. No abstract available. Erratum In: Eur Heart J. 2020 Nov 21;41(44):4255. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Major Adverse Cardiovascular Events (MACE)	Composite of all-cause death, non-fatal MI, non-fatal stroke, any revascularization, and hospitalization for angina	Within 3 years after the enrollment
Secondary	Change in coronary total plaque volume(mm³) on CCTA	Total plaque volume(mm³) is defined as the sum of all plaque volumes for coronary arteries.	Within 3 years after the enrollment
Secondary	Change in coronary plaque burden(%) on CCTA	Plaque burden(%)=(plaque area/vessel area)×100%	Within 3 years after the enrollment
Secondary	Changes in coronary plaque compositions(mm³, %) on CCTA	Plaque compositions include lipid(<30 HU), fibrous(30-150HU), and calcified plaque(>350HU).	Within 3 years after the enrollment
Secondary	Changes in coronary high-risk plaque characteristics on CCTA	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).	Within 3 years after the enrollment
Secondary	Change in coronary artery calcium score (CACS) on CT	CACS is a quantification of all coronary calcification by the scoring algorithm proposed by Agatston et al.	Within 3 years after the enrollment

External Links

•   China-PAR 10-year ASCVD risk model