Effect of Combined Lipid-lowering Therapy on Atherosclerotic Plaque Vulnerability in Patients With ACS
- Conditions
- Dyslipidemias
- Interventions
- Combination Product: Combined Lipid-lowering Therapy
- Registration Number
- NCT05624658
- Lead Sponsor
- Samara Regional Cardiology Dispensary
- 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).
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 200
- 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
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description PCSK9 inhibitors in combination Atorvastatin at a dose of 80 mg /Rosuvastatin 40 mg/ day Combined Lipid-lowering Therapy 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. Ezetimibe at a dose of 10 mg in combination with Atorvastatin 80 mg / Rosuvastatin 40 mg/ day. Combined Lipid-lowering Therapy Group 2 - receiving Ezetimibe at a dose of 10 mg in combination with Atorvastatin 80 mg / Rosuvastatin 40 mg/day.
- Primary Outcome Measures
Name Time Method Percent of change plaque vulnerability parameters on CCTA data 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")
- Secondary Outcome Measures
Name Time Method dynamics of level hs-CRP within 1 year (mg/l) 52 weeks blood sampling at the second visit and 12 months later
Total cholesterol, LDL-C, HDL-C, triglycerides levels after 52 weeks 52 weeks blood sampling at control visits every 3 months
dynamics of level MMP-9 within 1 year (ng/ml) 52 weeks blood sampling at the second visit and 12 months later
dynamics of level TIMP - 1 within 1 year (ng/ml) 52 weeks blood sampling at the second visit and 12 months later
dynamics of level hs-Troponin I within 1 year (ng/l) 52 weeks blood sampling at the second visit and 12 months later
dynamics of level NLR within 1 year 52 weeks blood sampling at the second visit and 12 months later
dynamics of level Galectin- 3 within 1 year (ng/ml) 52 weeks blood sampling at the second visit and 12 months later
dynamics of level NGAL within 1 year (ng/ml) 52 weeks blood sampling at the second visit and 12 months later
The number of participants with death, stent thrombosis/restenosis, nonfatal MI, hospitalization due to unstable angina, revascularization within 1 year 52 weeks assessment via telemedicine consultation every month and at follow-up visits every 3 months
Trial Locations
- Locations (1)
Samara Regional Cardiology Dispansery
🇷🇺Samara, Russian Federation