Further Lipid-Lowering With PCSK9 Inhibitors for Cardiovascular Outcomes in High-Risk Coronary Plaques Assessed by CT Angiography (FLAVOUR IV)

Zhejiang University

Status: Enrolling

Conditions: Coronary Artery Disease; CT Angiography; Cardiovascular Events; PCSK9

Treatments: Drug: PCSK9 inhibitors and background lipid-modifying therapy; Drug: Standard lipid-modifying therapy

Study type: Interventional

Funder types: Other

Identifiers

NCT06863545

2025-0052

Details and patient eligibility

About

The primary objective was to evaluate the effect of PCSK9 inhibitors in addition to the background lipid-modifying therapy (LMT), compared with standard LMT in terms of clinical outcomes in patients with coronary CT angiography (CCTA)-detected high-risk plaques.

Full description

CCTA is an accurate, noninvasive alternative to invasive coronary angiography. CCTA can provide detailed information about the characteristics of coronary artery plaques, such as their composition, morphology, and distribution. Various CCTA-detected plaque characteristics indicative of plaque quantity and quality have been identified as high-risk features independently predicting clinical events, including the presence of positive remodeling, low attenuation plaque, spotty calcification, and napkin ring sign. Currently, the treatment for CCTA-detected high-risk plaque has been receiving increasing interest. The current study aimed to prove the efficacy of PCSK9 inhibitors in addition to the background LMT, as compared with standard LMT in patients with CCTA-detected high-risk plaques.

Hypothesis: PCSK9 inhibitors in addition to background LMT will show a superior event rate, compared with standard LMT, in terms of major adverse cardiac and cerebrovascular events (MACCEs) at 24 months after the last patient's randomization in patients with high-risk coronary plaques assessed by CT Angiography.

Enrollment: 3,596 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Subject must be ≥ 18 years.

2. Patients with at least one target lesion meet CCTA-detected plaque features of the following:

   1. Degree of stenosis ≥ 50% or plaque burden ≥ 70%
   2. At least 2 of the following high-risk plaque features:

   i. Low-attenuation plaque ii. Positive remodeling iii. Napkin-ring sign iv. Spotty calcium

3. The target lesion is located at the proximal or mid segment of left anterior descending artery, left circumflex artery or right coronary artery.

4. Subject is able to confirm his/her understanding of the risks, benefits, and treatment alternatives of receiving study-related treatment. He/she or his/her legally authorized representative provides written informed consent prior to any study-related procedure.

Exclusion criteria

1. Target lesions underwent or planned to revascularization.
2. Patients with acute coronary syndrome.
3. New York Heart Association class III or IV, or last known left ventricular ejection fraction < 30%.
4. Uncontrolled or recurrent ventricular tachycardia.
5. Homozygous familial hypercholesterolemia.
6. Active liver disease or hepatic dysfunction.
7. Failed CCTA plaque analysis.
8. Non-cardiac co-morbid conditions with life expectancy < 2 years.
9. Pregnant and/or lactating women.
10. Known hypersensitivity or contraindication to statin or PCSK9 inhibitors.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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3,596 participants in 2 patient groups

PCSK9 inhibitors plus background lipid-modifying therapy

Experimental group

Description:

Patients will receive PCSK9 inhibitors treatment and background lipid-modifying therapy for the first 12 months after randomization, and then continue background lipid-modifying therapy for the remainder of the trial.

Standard lipid-modifying therapy

Active Comparator group

Description:

Patients will receive standard LMT commonly used in clinical practice.

Treatment:

Drug: Standard lipid-modifying therapy