Effect of Combined Lipid-lowering Therapy on Atherosclerotic Plaque Vulnerability in Patients With ACS

NCT ID: NCT05624658

Last Updated: 2023-11-18

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 200 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-09-02
• Study Completion Date: 2024-05-31

Brief Summary

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.

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).

Conditions

Dyslipidemias

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

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.

Group Type: ACTIVE_COMPARATOR

Combined Lipid-lowering Therapy

Intervention Type: COMBINATION_PRODUCT

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.

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.

Group Type: ACTIVE_COMPARATOR

Combined Lipid-lowering Therapy

Intervention Type: COMBINATION_PRODUCT

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.

Interventions

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.

Intervention Type: COMBINATION_PRODUCT

Other Intervention Names

invasive coronary angiography, coronary artery commputed tomography, OCT, CAVI index

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Samara State Medical University

OTHER

Sponsor Role: collaborator

Samara Regional Cardiology Dispensary

OTHER

Sponsor Role: lead

Responsible Party

Prof. Dmitry Duplyakov FESC

Medical Director

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Dmitry Duplyakov

Role: PRINCIPAL_INVESTIGATOR

Samara State Medical Universiry

Locations

Samara Regional Cardiology Dispansery

Samara, , Russia

Site Status: RECRUITING

Countries

Russia

Central Contacts

Dmitry Duplyakov, professor

Role: CONTACT

duplyakov@yahoo.com

+79277297273

Anna Kovalskaya

Role: CONTACT

kovalskaya.an@gmail.com

+79270130848

Facility Contacts

Dmitry Duplyakov

Role: primary

Other Identifiers

SamaraRCD-1

Identifier Type: -

Identifier Source: org_study_id