Early Intensive Lipid-Lowering With Inclisiran for Plaque Stabilization in Acute Coronary Syndrome (SEsiR-ACS)

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Acute Coronary Syndromes (ACS)
• Intervention / Treatment: Drug: Inclisiran; Drug: Atorvastatin or Rosuvastatin; Drug: Ezetimibe

• Study Type: Interventional
• Enrollment (Estimated): 294
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Chang-Hwan Yoon, MD, PhD; Phone Number: +82-031-787-7019; Email: changhwanyoon@gmail.com

Study Locations

• South Korea
  • Gyeonggi-do
    • Seongnam-si, Gyeonggi-do, South Korea, 13620
      • Seoul National University Bundang Hospital
      • Contact: Chang-Hwan Yoon; Phone Number: +82-031-787-7019; Email: changhwanyoon@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

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
Experimental: Early Intensive Lipid-Lowering Strategy; Participants will receive an early intensive lipid-lowering strategy consisting of a high-intensity statin, ezetimibe 10 mg once daily, and inclisiran 284 mg by subcutaneous injection initiated during the index hospitalization or as early as feasible. Inclisiran will be repeated at 3 months and 9 months.	Drug: Inclisiran; Inclisiran sodium 284 mg/1.5 mL will be administered by subcutaneous injection in the early intensive lipid-lowering group. Inclisiran will be initiated during the index hospitalization or as early as feasible thereafter, within 2 weeks, followed by additional doses at 3 months (±2 weeks) and 9 months (±2 weeks).; Drug: Atorvastatin or Rosuvastatin; High-intensity statin therapy will consist of atorvastatin 40-80 mg orally once daily or rosuvastatin 20 mg orally once daily, or the maximally tolerated dose. High-intensity statin therapy will be initiated or continued during the index hospitalization in both treatment groups.; Drug: Ezetimibe; Ezetimibe 10 mg will be administered orally once daily. In the early intensive lipid-lowering group, ezetimibe will be initiated during the index hospitalization. In the guideline-based stepwise intensification group, ezetimibe will be added according to follow-up LDL-C levels if the treatment target is not achieved with high-intensity statin therapy.
Active Comparator: Guideline-Based Stepwise Intensification Strategy; Participants will receive a guideline-based stepwise lipid-lowering strategy. High-intensity statin therapy will be initiated or continued during the index hospitalization. Ezetimibe will be added according to follow-up LDL-C levels, and a PCSK9 inhibitor may be considered if the LDL-C target remains unmet.	Drug: Atorvastatin or Rosuvastatin; High-intensity statin therapy will consist of atorvastatin 40-80 mg orally once daily or rosuvastatin 20 mg orally once daily, or the maximally tolerated dose. High-intensity statin therapy will be initiated or continued during the index hospitalization in both treatment groups.; Drug: Ezetimibe; Ezetimibe 10 mg will be administered orally once daily. In the early intensive lipid-lowering group, ezetimibe will be initiated during the index hospitalization. In the guideline-based stepwise intensification group, ezetimibe will be added according to follow-up LDL-C levels if the treatment target is not achieved with high-intensity statin therapy.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Minimal Fibrous Cap Thickness	Change from baseline to 12 months in minimal fibrous cap thickness (FCT), measured by optical coherence tomography (OCT) in one prespecified representative matched non-stented coronary plaque or segment per participant.	Baseline to 12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in OCT-Derived Lipid Plaque Characteristics	Changes from baseline to 12 months in maximum lipid arc, mean lipid arc, lipid length, lipid index, and the prevalence of thin-cap fibroatheroma (TCFA), assessed by optical coherence tomography (OCT) in matched non-stented coronary plaque segments.	Baseline to 12 months
Change in Lipid Parameters and LDL-C Target Attainment	Absolute and percentage changes in LDL-C from baseline during follow-up, achievement of the prespecified LDL-C target, defined as LDL-C <40 mg/dL and a reduction of at least 50% from baseline, and changes in non-HDL-C, hsCRP, and, when available, ApoB and Lp(a).	Baseline to 12 months
Changes in IVUS-Derived Plaque Burden in the IVUS Substudy	Change from baseline to 12 months in percent atheroma volume (PAV), assessed by intravascular ultrasound (IVUS) in matched non-stented coronary segments. Additional IVUS assessments include changes in total atheroma volume (TAV) and plaque burden.	Baseline to 12 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Exploratory Clinical Events	Exploratory clinical events will include cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, unplanned revascularization, and hospitalization. Event numbers and cumulative incidence rates will be assessed during follow-up.	Up to 12 months

Collaborators and Investigators

• Sponsor: Seoul National University Bundang Hospital
• Collaborators: Hanmi Pharmaceutical co., ltd.; Novartis Korea Ltd.; Dotter Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Estimated): September 1, 2026
• Primary Completion (Estimated): September 1, 2029
• Study Completion (Estimated): September 1, 2029

Study Registration Dates

• First Submitted: August 28, 2026
• First Submitted That Met QC Criteria: August 28, 2026
• First Posted (Actual): September 2, 2026

Study Record Updates

• Last Update Posted (Actual): September 2, 2026
• Last Update Submitted That Met QC Criteria: August 28, 2026
• Last Verified: August 1, 2026

More Information

Terms related to this study

• Keywords: Inclisiran; Optical Coherence Tomography; Atherosclerotic Plaque; Lipid-Lowering Therapy; Coronary Plaque Stabilization; Fibrous Cap Thickness
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Pathological Conditions, Anatomical; Heart Diseases; Myocardial Ischemia; Pathological Conditions, Signs and Symptoms; Plaque, Atherosclerotic; Acute Coronary Syndrome; Sulfur Compounds; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fatty Acids; Lipids; Azoles; Hydrocarbons; Amides; Pyrimidines; Hydrocarbons, Halogenated; Pyrroles; Heptanoic Acids; Sulfonamides; Sulfones; Azetidines; Azetines; Fluorobenzenes; Hydrocarbons, Fluorinated; Atorvastatin; Rosuvastatin Calcium; Ezetimibe; ALN-PCS
• Other Study ID Numbers: B-2607-1057-003

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