Early Intensive Lipid-Lowering With Inclisiran for Plaque Stabilization in Acute Coronary Syndrome

Statin, Ezetimibe, and Inclisiran for Plaque Regression in Acute Coronary Syndrome: A Randomized Controlled Trial (SEsiR-ACS Trial)

This multicenter, randomized, open-label clinical trial will evaluate whether an early intensive lipid-lowering strategy can improve coronary plaque stabilization in patients hospitalized with acute coronary syndrome. A total of 294 participants will be randomly assigned in a 1:1 ratio to either an early intensive treatment strategy with a high-intensity statin, ezetimibe, and inclisiran, or a guideline-based stepwise lipid-lowering strategy.

Coronary plaque characteristics will be assessed using optical coherence tomography (OCT) at baseline and at 12 months. The primary outcome is the change in minimal fibrous cap thickness from baseline to 12 months. Additional assessments will include other OCT-based plaque characteristics, lipid levels, safety outcomes, and, in a subset of participants, intravascular ultrasound measurements of plaque burden.

Inclusion Criteria:

1. Age 19 to 85 years.

2. Hospitalization for acute coronary syndrome (UA, NSTEMI, or STEMI) with planned coronary angiography and PCI, or PCI already performed during the index hospitalization with adequate baseline OCT images obtained during the procedure that meets the study imaging analysis criteria.

3. Presence of a target vessel/segment considered by the investigator to be suitable for OCT assessment at baseline and at the 12-month follow-up.

4. LDL-C level at screening meeting one of the following criteria according to background lipid-lowering therapy:

   i) ≥40 mg/dL in patients receiving stable combination therapy with a statin and ezetimibe, defined as no dose change for at least 4 weeks before screening; ii) ≥55 mg/dL in patients receiving high-intensity statin therapy; iii) ≥70 mg/dL in patients receiving low- or moderate-intensity statin therapy; or iv) ≥100 mg/dL in patients not receiving stable statin therapy.

5. Provision of voluntary written informed consent after receiving sufficient information regarding the study objectives, procedures, and follow-up plan.

Exclusion Criteria:

1. Severe hepatic dysfunction, defined as AST or ALT >3 times the upper limit of normal.
2. CK >5 times the upper limit of normal or suspected clinically significant myopathy.
3. Severe renal impairment, defined as eGFR <30 mL/min/1.73 m².
4. Severe hypersensitivity to or contraindication to statins, ezetimibe, or inclisiran.
5. Pregnancy, breastfeeding, or plans to become pregnant during the study period.
6. Inability to undergo 12-month follow-up coronary angiography and OCT.
7. Life expectancy <1 year or, in the investigator's judgment, inappropriate participation in the study because of concerns regarding adherence or safety.