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

Обзор

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.

Подробное описание

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.

Вмешательства

• Препарат PCSK9 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.
• Препарат Standard lipid-modifying therapy
  Patients will receive standard LMT commonly used in clinical practice.

Первичные конечные точки

• Major adverse cardiac and cerebrovascular events (MACCEs) [Срок оценки: 24 months after the last patient's randomization]

Вторичные конечные точки (10)

• MACCEs [Срок оценки: 60 months after the last patient's randomization]
• Individual component of MACCEs. [Срок оценки: 24 and 60 months after the last patient's randomization]
• Major adverse cardiovascular events (MACEs) [Срок оценки: 24 and 60 months after the last patient's randomization]
• Target vessel failure (TVF) [Срок оценки: 24 and 60 months after the last patient's randomization]
• Cost-effectiveness analysis [Срок оценки: 24 and 60 months after the last patient's randomization]
• All-cause and cardiac death. [Срок оценки: 24 and 60 months after the last patient's randomization]
• Any target-vessel MI. [Срок оценки: 24 and 60 months after the last patient's randomization]
• Any target vessel revascularization. [Срок оценки: 24 and 60 months after the last patient's randomization]
• Any coronary revascularization (ischemia-driven or all). [Срок оценки: 24 and 60 months after the last patient's randomization]
• CT coronary angiography findings [Срок оценки: 36 months after the last patient's randomization]

Критерии участия

Критерии включения

• Subject must be ≥ 18 years.
• Patients with at least one target lesion meet CCTA-detected plaque features of the following:

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

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

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

Критерии исключения

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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Простое слепое

Основная цель

Лечение

Центры проведения

Китай · 5 центров

• Zhejiang Provincial Hospital of Traditional Chinese Medicine — Ханчжоу
• Hangzhou Linping First People's Hospital — Ханчжоу
• The Second Affiliated Hospital, School of Medicine, Zhejiang University — Ханчжоу
• Zhejiang Hospital — Ханчжоу
• Jinhua Central Hospital — Jinhua

South Korea · 1 центр

• Seoul National University Hospital — Seoul

Публикации

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Идентификаторы

NCT: NCT06863545 · 2025-0052

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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