Impact of Optimal Pharmacotherapy on Plasma Lipid Profile and Qualitative Features of Atherosclerotic Plaques in Very-high Cardiovascular Risk Patients With Established Atherosclerotic Cardiovascular Disease
试验速览
- 阶段
- 不适用
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 50
- 试验地点
- 1
- 主要终点
- LDL-C level
研究概览
简要总结
Lipid accumulation, with mostly emphasized role of low-density lipoprotein cholesterol (LDL-C), is the pathogenetic cornerstone of atherosclerotic cardiovascular disease. Standard hypolipidemic therapy, based on statins and ezetimibe, does not always decrease LDL-C levels enough to achieve therapeutic goals. A novel and promising direction is inhibition of proprotein convertase subtilisin/kexin type 9 (PCSK9) in hepatocytes, subsequently reducing LDL-C receptor degradation and increasing intracellular LDL-C uptake.
Aim of this study is to evaluate the effect of optimal hypolipidemic pharmacotherapy, including PCSK9 inhibitors and inclisiran, on plasma lipid profile and qualitative features of atherosclerotic plaques in very-high cardiovascular risk patients.
This study enrolls patients with an established atherosclerotic cardiovascular disease, receiving PCSK9 inhibitors or inclisiran as add-on treatment to statins in maximally tolerated dose and/or ezetimibe.
Effect of hypolipidemic pharmacotherapy is evaluated by analysis of plasma lipid profile parameter changes and qualitative features of atherosclerotic plaques using Near-Infrared Spectroscopy Intravascular Ultrasound Imaging (NIRS-IVUS) method.
Results of the study would be sufficient for complementing evidence regarding therapeutic strategy in very-high cardiovascular risk patients.
详细描述
Background:
Lipid accumulation in artery walls is the pathogenetic cornerstone of atherosclerosis. The most commonly studied risk factor of atherosclerotic cardiovascular disease is low-density lipoprotein cholesterol (LDL-C), nevertheless other plasma lipids have an established role as well. LDL-C is considered the primary target for cardiovascular risk reduction, with therapeutic goal <1.4 mmol/l in very-high cardiovascular risk patients with established atherosclerotic cardiovascular disease. Standard hypolipidemic therapy, based on statins and ezetimibe, is not always effective enough. Novel and promising direction is proprotein convertase subtilisin/kexin type 9 (PCSK9) - protease that binds LDL receptors in hepatocytes, subsequently promoting their lysosomal degradation. This process leads to reduced intracellular LDL-C uptake and increased LDL-C concentration in plasma. PCSK9 inhibitors - monoclonal antibodies evolocumab and alirocumab are successfully used in clinical practice, with a proven effectiveness in clinical trials ODYSSEY and FOURIER. An innovative medication is inclisiran - small interfering ribonucleic acid (siRNA) molecule that interferes with translation of messenger RNA (mRNA) of PCSK9 in hepatocytes as a result of complementary binding. Subsequently levels of synthesized PCSK9 are reduced, resulting in positive impact on plasma lipid profile. Inclisiran has demonstrated remarkable efficacy and safety profile in ORION clinical trials, being registered in European Medicines Agency since year 2020. Real-world data regarding optimal lipid-lowering pharmacotherapy, including experience with new medications, is of great clinical interest, studying effect on plasma lipid profile, as well as qualitative features of atherosclerotic plaques using Near-Infrared Spectroscopy Intravascular Ultrasound Imaging (NIRS-IVUS) method.
Aim:
Aim of this study is to evaluate effect of optimal hypolipidemic pharmacotherapy on plasma lipid profile and and qualitative features of atherosclerotic plaques in very-high cardiovascular risk patients receiving PCSK9 inhibitors or inclisiran as add-on treatment to statins in maximally tolerated dose and/or ezetimibe.
Study design:
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Very high cardiovascular risk - documented atherosclerotic cardiovascular disease
- •On maximally tolerated statin and/or ezetimibe therapy for at least 1 month LDL-C treatment target <1.4 mmol/l not achieved
- •Receiving PCSK9 inhibitor or inclisiran as add-on treatment to maximally tolerated statin dose and/or ezetimibe in the context of optimal pharmacotherapy
- •NIRS-IVUS performed (written informed consent for the procedure signed according to regulations in the hospital)
- •Available blood test results - plasma lipid profile
- •Patient agrees to participate in the study (signed informed consent)
排除标准
- •Not fulfilling any of inclusion criteria
结局指标
主要结局
LDL-C level
时间窗: 15 months
Plasma LDL-C level changes in patients receiving PCSK9 inhibitors or inclisiran
Qualitative features of atherosclerotic plaques
时间窗: 15 months
Changes in qualitative features of atherosclerotic plaques assessed by NIRS-IVUS investigation
次要结局
未报告次要终点
研究者
Karlis Trusinskis
MD
Pauls Stradins Clinical University Hospital