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)
试验速览
- 阶段
- 不适用
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 2,900
- 试验地点
- 2
- 主要终点
- Major Adverse Cardiovascular Events (MACE)
研究概览
简要总结
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 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.
详细描述
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 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. 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 the control group (goal for LDL-C <2.6 mmol/L or 30%-50% reduction from baseline).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Single (Outcomes Assessor)
盲法说明
blinded endpoint
入排标准
- 年龄范围
- 40 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age 40-75 years
- •Low to Intermediate 10-year atherosclerotic cardiovascular disease (ASCVD) risk using pooled cohort equations (PCE).
- •Coronary CT angiography shows atherosclerotic plaque in the main coronary vessels (>2mm diameter) with luminal stenosis <70%
排除标准
- •Combination with serious cardiovascular diseases, including
- •Heart failure (ejection fraction <30%)
- •Arrhythmias (persistent atrial flutter/atrial fibrillation, second-degree or third-degree atrioventricular block)
- •Hemodynamically important valvular disease
- •Hemodynamically important congenital heart disease
- •Myocardial infarction, coronary revascularization, or severe/unstable angina before or within 1 month of screening
- •Active liver disease or hepatic dysfunction (defined as alanine aminotransferase or aspartate aminotransferase> 3 times the upper limit of normal)
- •Unexplained creatine phosphokinase> 6 times the upper limit of normal
- •Nephrotic syndrome
- •Diabetes mellitus
- •Uncontrollable hypertension
- •Uncontrollable hypothyroidism
- •Hypersensitivity to statins
- •Any planned surgical procedure for the treatment of atherosclerosis
- •Gastrointestinal diseases affecting drug absorption or history of gastrointestinal surgery
- •Survival-limiting diseases
- •Concurrent long-term immunosuppressive therapy
- •Participation in another clinical trial concurrently or within 30 days before screening
- •Pregnant or breastfeeding
- •Other unsuitable situations deemed by physicians
研究组 & 干预措施
intensive lipid-lowering group
Goal for LDL-C <1.8 mmol/L or ≥50% reduction from baseline.
干预措施: Intensive lipid-lowering control (Drug)
moderate-intensity lipid-lowering group
Goal for LDL-C <2.6 mmol/L or 30%-50% reduction from baseline.
干预措施: Moderate-intensity lipid-lowering control (Drug)
结局指标
主要结局
Major Adverse Cardiovascular Events (MACE)
时间窗: Within 3 years after the enrollment
Composite of all-cause death, non-fatal MI, non-fatal stroke, any revascularization, and hospitalization for angina
次要结局
- Change in coronary artery calcium score (CACS) on CT(Within 3 years after the enrollment)
- Change in coronary total plaque volume(mm³) on CCTA(Within 3 years after the enrollment)
- Change in coronary plaque burden(%) on CCTA(Within 3 years after the enrollment)
- Changes in coronary plaque compositions(mm³, %) on CCTA(Within 3 years after the enrollment)
- Changes in coronary high-risk plaque characteristics on CCTA(Within 3 years after the enrollment)
研究者
Bin Lu
Principle Investigator of National Center for Cardiovascular Diseases and National Clinical Research Center of Cardiovascular Diseases
Chinese Academy of Medical Sciences, Fuwai Hospital