Effect of Combined Lipid-lowering Therapy on Atherosclerotic Plaque Vulnerability in Patients With ACS (Combi-LLT ACS)

Effect of Combined Lipid-lowering Therapy on Atherosclerotic Plaque Vulnerability in Patients With Acute Coronary Syndrome, a Prospective, Open-label, Randomized, Single-center Study

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.

Study Overview

• Status: Recruiting
• Conditions: Dyslipidemias
• Intervention / Treatment: Combination product: Combined Lipid-lowering Therapy

Detailed Description

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).

• Study Type: Interventional
• Enrollment (Estimated): 200
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Dmitry Duplyakov, professor; Phone Number: +79277297273; Email: duplyakov@yahoo.com
• Study Contact Backup: Name: Anna Kovalskaya; Phone Number: +79270130848; Email: kovalskaya.an@gmail.com

Study Locations

• Russian Federation
  • Samara, Russian Federation, 443070
    • Recruiting
    • Samara Regional Cardiology Dispansery
    • Contact: Dmitry Duplyakov
    • Sub-Investigator: Anna Kovalskaya
    • Sub-Investigator: Guzel Bikbaeva

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 73 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: PCSK9 inhibitors in combination Atorvastatin at a dose of 80 mg /Rosuvastatin 40 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./ Rosuvastatin 40 mg / day.	Combination product: Combined Lipid-lowering Therapy; the effect of high-dose combined lipid-lowering therapy (statins+ezetimibe vs statins+PCSK9 inhibitors) on the vulnerability characteristics of atherosclerotic plaques assessed using multimodal imaging (coronary artery computed tomography and optical coherence tomography), as well as biomarkers in patients with acute coronary syndrome for 52 weeks.; Other Names: invasive coronary angiography, coronary artery commputed tomography, OCT, CAVI index
Active Comparator: Ezetimibe at a dose of 10 mg in combination with Atorvastatin 80 mg / Rosuvastatin 40 mg/ day.; Group 2 - receiving Ezetimibe at a dose of 10 mg in combination with Atorvastatin 80 mg / Rosuvastatin 40 mg/day.	Combination product: Combined Lipid-lowering Therapy; the effect of high-dose combined lipid-lowering therapy (statins+ezetimibe vs statins+PCSK9 inhibitors) on the vulnerability characteristics of atherosclerotic plaques assessed using multimodal imaging (coronary artery computed tomography and optical coherence tomography), as well as biomarkers in patients with acute coronary syndrome for 52 weeks.; Other Names: invasive coronary angiography, coronary artery commputed tomography, OCT, CAVI index

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent of change plaque vulnerability parameters on CCTA data	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")	52 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The number of participants with death, stent thrombosis/restenosis, nonfatal MI, hospitalization due to unstable angina, revascularization within 1 year	assessment via telemedicine consultation every month and at follow-up visits every 3 months	52 weeks
Total cholesterol, LDL-C, HDL-C, triglycerides levels after 52 weeks	blood sampling at control visits every 3 months	52 weeks
dynamics of level hs-Troponin I within 1 year (ng/l)	blood sampling at the second visit and 12 months later	52 weeks
dynamics of level hs-CRP within 1 year (mg/l)	blood sampling at the second visit and 12 months later	52 weeks
dynamics of level NLR within 1 year	blood sampling at the second visit and 12 months later	52 weeks
dynamics of level Galectin- 3 within 1 year (ng/ml)	blood sampling at the second visit and 12 months later	52 weeks
dynamics of level MMP-9 within 1 year (ng/ml)	blood sampling at the second visit and 12 months later	52 weeks
dynamics of level TIMP - 1 within 1 year (ng/ml)	blood sampling at the second visit and 12 months later	52 weeks
dynamics of level NGAL within 1 year (ng/ml)	blood sampling at the second visit and 12 months later	52 weeks

Collaborators and Investigators

• Sponsor: Samara Regional Cardiology Dispensary
• Collaborators: Samara State Medical University
• Investigators: Principal Investigator: Dmitry Duplyakov, Samara State Medical Universiry

Study record dates

Study Major Dates

• Study Start (Actual): September 2, 2022
• Primary Completion (Estimated): May 1, 2024
• Study Completion (Estimated): May 1, 2024

Study Registration Dates

• First Submitted: November 8, 2022
• First Submitted That Met QC Criteria: November 17, 2022
• First Posted (Actual): November 22, 2022

Study Record Updates

• Last Update Posted (Actual): November 18, 2023
• Last Update Submitted That Met QC Criteria: November 16, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: PCI; acute coronary syndrome; Ezetimibe; plaque vulnerability; PCSK9 inhibitors; combined lipid-lowering therapy; coronary artery computed tomography
• Additional Relevant MeSH Terms: Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Metabolic Diseases; Pathological Conditions, Anatomical; Lipid Metabolism Disorders; Dyslipidemias; Acute Coronary Syndrome; Plaque, Atherosclerotic
• Other Study ID Numbers: SamaraRCD-1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No