Clinical trial NCT05624658: Effect of Combined Lipid-lowering Therapy on Atherosclerotic Plaque Vulnerability in Patients With ACS
Official title: Effect of Combined Lipid-lowering Therapy on Atherosclerotic Plaque Vulnerability in Patients With Acute Coronary Syndrome, a Prospective, Open-label, Randomized, Single-center Study
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Dyslipidemias
Keywords: acute coronary syndrome
PCI
plaque vulnerability
combined lipid-lowering therapy
PCSK9 inhibitors
Ezetimibe
coronary artery computed tomography
Lead sponsor: Samara Regional Cardiology Dispensary
Sponsor class: OTHER
Collaborators: name: Samara State Medical University
First posted: 2022-11-22
Enrollment: 200
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Patients who 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 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 CCTA, an 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 period will be 52 weeks, according to the schedule of visits. At the final visit, patients will undergo CCTA, assess the CAVI index and laboratory tests (blood count, lipid profile, Troponin I, Galectin-3, MMP-9, TIMP-1, high-sensitivity CRP, NGAL).
Primary purpose: TREATMENT

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).

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

Primary outcomes:
measure: Percent of change plaque vulnerability parameters on CCTA data
timeFrame: 52 weeks
Secondary outcomes:
measure: The number of participants with death, stent thrombosis/restenosis, nonfatal MI, hospitalization due to unstable angina, revascularization within 1 year
timeFrame: 52 weeks
measure: Total cholesterol, LDL-C, HDL-C, triglycerides levels after 52 weeks
timeFrame: 52 weeks
measure: dynamics of level hs-Troponin I within 1 year (ng/l)
timeFrame: 52 weeks
measure: dynamics of level hs-CRP within 1 year (mg/l)
timeFrame: 52 weeks
measure: dynamics of level NLR within 1 year
timeFrame: 52 weeks
measure: dynamics of level Galectin- 3 within 1 year (ng/ml)
timeFrame: 52 weeks
measure: dynamics of level MMP-9 within 1 year (ng/ml)
timeFrame: 52 weeks
measure: dynamics of level TIMP - 1 within 1 year (ng/ml)
timeFrame: 52 weeks
measure: dynamics of level NGAL within 1 year (ng/ml)
timeFrame: 52 weeks
Other outcomes:
Locations:
city: Samara
country: Russian Federation
facility: Samara Regional Cardiology Dispansery
Study officials:
affiliation: Samara State Medical Universiry
name: Dmitry Duplyakov
role: PRINCIPAL_INVESTIGATOR
References: