Cardiovascular Events, Coronary Artery Disease, CT Angiography, PCSK9
Conditions
Keywords
PCSK9 inhibitors, Lipid-lowering therapy, High-Risk Coronary Plaques, Coronary CT angiography
Brief summary
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.
Detailed 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.
Interventions
DRUGPCSK9 inhibitors and background lipid-modifying therapy
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.
DRUGStandard lipid-modifying therapy
Patients will receive standard LMT commonly used in clinical practice.
Sponsors
Second Affiliated Hospital, School of Medicine, Zhejiang University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Major adverse cardiac and cerebrovascular events (MACCEs) | 24 months after the last patient's randomization | A composite of death from any cause, myocardial infarction (MI), coronary revascularization, or stroke. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| MACCEs | 60 months after the last patient's randomization | a composite of death from any cause, MI, coronary revascularization, or stroke. |
| Individual component of MACCEs. | 24 and 60 months after the last patient's randomization | Individual component of MACCEs (death from any cause, MI, coronary revascularization, or stroke) |
| Major adverse cardiovascular events (MACEs) | 24 and 60 months after the last patient's randomization | Defined as a composite of death from any cause, MI, coronary revascularization. |
| Target vessel failure (TVF) | 24 and 60 months after the last patient's randomization | Defined as a composite of cardiac death, target-vessel MI, or target vessel revascularization |
| Cost-effectiveness analysis | 24 and 60 months after the last patient's randomization | Cost-effectiveness analysis |
| All-cause and cardiac death. | 24 and 60 months after the last patient's randomization | All-cause and cardiac death. |
| Any target-vessel MI. | 24 and 60 months after the last patient's randomization | Any target-vessel MI. |
| Any target vessel revascularization. | 24 and 60 months after the last patient's randomization | Any target vessel revascularization. |
| Any coronary revascularization (ischemia-driven or all). | 24 and 60 months after the last patient's randomization | Any coronary revascularization (ischemia-driven or all). |
| CT coronary angiography findings | 36 months after the last patient's randomization | Changes in the CT-derived fractional flow reserve, lumen, plaque quantity and quality between baseline. |
Countries
China, South Korea
Contacts
CONTACTXinyang Hu
CONTACTJian'an Wang
PRINCIPAL_INVESTIGATORXinyang Hu
Second Affiliated Hospital, School of Medicine, Zhejiang University
PRINCIPAL_INVESTIGATORBon-Kwon Koo
Seoul National University Hospital
Outcome results
None listed