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

Second Affiliated Hospital, Zhejiang University, School of Medicine3,596 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

SINGLE

Enrollment

3,596

Conditions

Coronary Artery Disease

Interventions

PCSK9 inhibitors and background lipid-modifying therapyDRUG

Patients will receive subcutaneous injections of PCSK9 inhibitors and oral administration of background LMT (including statins and/or cholesterol absorption inhibitors) for the first 12 months after randomization, with PCSK9 inhibitors administered every 2 weeks. After the first 12 months, patients will discontinue the PCSK9 inhibitors but continue background LMT for the remainder of the trial.

Standard lipid-modifying therapyDRUG

Patients will receive standard LMT commonly used in clinical practice.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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.

Locations (6)

Zhejiang Provincial Hospital of Traditional Chinese Medicine

Hangzhou, Zhejiang, China

RECRUITING

Hangzhou Linping First People's Hospital

Hangzhou, China

RECRUITING

The Second Affiliated Hospital, School of Medicine, Zhejiang University

Hangzhou, China

RECRUITING

Zhejiang Hospital

Hangzhou, China

RECRUITING

Jinhua Central Hospital

Jinhua, China

RECRUITING

Seoul National University Hospital

Seoul, South Korea

NOT_YET_RECRUITING

Outcomes

Primary Outcomes

Major adverse cardiac and cerebrovascular events (MACCEs)

A composite of death from any cause, myocardial infarction (MI), coronary revascularization, or stroke.

Time frame: 24 months after the last patient's randomization

Secondary Outcomes

MACCEs

a composite of death from any cause, MI, coronary revascularization, or stroke.

Time frame: 60 months after the last patient's randomization

Individual component of MACCEs.

Individual component of MACCEs (death from any cause, MI, coronary revascularization, or stroke)