Effect of Combined Lipid-lowering Therapy on Atherosclerotic Plaque Vulnerability in Patients With Acute Coronary Syndrome, a Prospective, Open-label, Randomized, Single-center Study
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 200
- 试验地点
- 2
- 主要终点
- Percent of change plaque vulnerability parameters on CCTA data
研究概览
简要总结
The study is prospective, open-label, randomized, single-center study involving patients admitted on an emergency basis with an acute coronary syndrome (ACS) clinic who underwent PCI of an infarct-related artery (IRA) and had intermediate coronary artery lesions (50-70% stenosis diameter) and elevated LDL-C ( > 1.4 mmol/l) despite statin therapy at the highest dosage. Patients who showed high compliance and did not reach the target LDL-C values 1 month after the development of ACS on the 2nd visit will be randomized into two groups of 60 patients each. Group 1 - taking PCSK9 inhibitors (Alirocumab 150 mg by subcutaneous injection once every 2 weeks or Evolocumab 140 mg by subcutaneous injection once every 2 weeks - open-label prescription of drugs) while taking Atorvastatin at a dose of 80 mg / day. Group 2 - receiving Ezetimibe at a dose of 10 mg in combination with Atorvastatin 80 mg / day.
详细描述
The study will enroll 120 patients with ACS admitted on an emergency basis to the Hospital. All patients will undergo PCI of the infarct-related artery (IRA), as well as intracoronary imaging with OCT of one or two non-IRA. During hospitalization, patients will receive standard therapy of ACS according to clinical recommendations, while Atorvastatin will initially be prescribed at a maximum dosage of 80 mg / day. Patients who showed high compliance and did not reach the target LDL-C values 1 month after the development of ACS on the 2nd visit will be randomized into two groups of 60 patients each. Group 1 - taking PCSK9 inhibitors (Alirocumab 150 mg by subcutaneous injection once every 2 weeks or Evolocumab 140 mg by subcutaneous injection once every 2 weeks - open-label prescription of drugs) while taking Atorvastatin at a dose of 80 mg / day. Group 2 - receiving Ezetimibe at a dose of 10 mg in combination with Atorvastatin 80 mg / day.
Also, on the 2nd visit, patients will undergo coronary artery computed tomography (CCTA): assessment of the CAVI index and a laboratory tests (blood count, lipid profile, ALAT, ASAT, Troponin I, Galectin -3, MMP -9, TIMP -1, high-sensitivity CRP, NGAL ). Every 3 months a visit is planned according to the schedule to monitor the effectiveness (blood count, ALAT, ASAT, lipid profile).
Follow up duration will be 52 weeks, according to the schedule of visits. At the final visit, patients will undergo CCTA, CAVI index and laboratory tests (blood count, lipid profile, ALAT, ASAT, Troponin I, Galectin -3, MMP -9, TIMP -1, high-sensitivity CRP, NGAL).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Single (Investigator)
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •gender (any);
- •age 18-75 years;
- •admission < 24 hours after pain onset
- •acute coronary syndrome with at least one coronary artery stenosis requiring PCI;
- •one or two non-IRA (coronary artery lumen diameter according to CAG >20% and <50% and no need for revascularization within the next 6 months according to the investigator)
- •not taking statins for at least 3 (6) months or not achieving the target level of LDL-C at admission
- •failure to achieve the target level of LDL-C ≥1.4 mmol/l on the second visit;
- •signed informed consent
排除标准
- •previous MI
- •history of revascularization (PCI/CABG)
- •presence of non-IRA stenoses ≥50%.
- •multivessel lesion, including significant stenosis of the LM
- •EF < 40%,
- •Killip III-IV.
- •NYHA III-IV
- •significant calcification or tortuosity of the coronary arteries, limiting OCT
- •intolerance to statins, aspirin, P2Y12 inhibitors
- •patients who have previously received PCSK9 inhibitors and/or Ezetimib
- •treatment with systemic steroids or systemic cyclosporine within the last 3 months
- •collagenoses and inflammatory diseases,
- •oncological diseases within the last 5 years,
- •scheduled surgery within 3 months
- •persons suffering from mental disorders
- •pregnancy, breastfeeding period
结局指标
主要结局
Percent of change plaque vulnerability parameters on CCTA data
时间窗: 52 weeks
change plaque vulnerability parameterson coronary artery computed tomography in non-IRA coronary arteries (positive remodeling; the presence of a low-density area in the plaque (less than 30 HU \*); point calcifications in the composition of the plaque; ring-shaped enhancement of X-ray density along the periphery of the plaque, not exceeding 130 HU, or the phenomenon of "circular glow")
次要结局
- Total cholesterol, LDL-C, HDL-C, triglycerides levels after 52 weeks(52 weeks)
- dynamics of level MMP-9 within 1 year (ng/ml)(52 weeks)
- dynamics of level TIMP - 1 within 1 year (ng/ml)(52 weeks)
- dynamics of level hs-Troponin I within 1 year (ng/l)(52 weeks)
- dynamics of level NLR within 1 year(52 weeks)
- dynamics of level Galectin- 3 within 1 year (ng/ml)(52 weeks)
- dynamics of level NGAL within 1 year (ng/ml)(52 weeks)
- The number of participants with death, stent thrombosis/restenosis, nonfatal MI, hospitalization due to unstable angina, revascularization within 1 year(52 weeks)
- dynamics of level hs-CRP within 1 year (mg/l)(52 weeks)
研究者
Prof. Dmitry Duplyakov FESC
Medical Director
Samara Regional Cardiology Dispensary