Acute Coronary Syndromes (ACS)
Conditions
Keywords
Inclisiran, Lipid-Lowering Therapy, Optical Coherence Tomography, Fibrous Cap Thickness, Coronary Plaque Stabilization, Atherosclerotic Plaque
Brief summary
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.
Interventions
DRUGInclisiran
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).
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.
DRUGEzetimibe
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.
Sponsors
Seoul National University Bundang Hospital
Dotter Co., Ltd.
Novartis Korea Ltd.
Hanmi Pharmaceutical co., ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Masking description
Participants and investigators are aware of treatment-group assignment. However, OCT images are analyzed by an independent imaging core laboratory blinded to treatment allocation, and major clinical events are adjudicated by an independent Clinical Event Committee blinded to treatment assignment.
Intervention model description
Participants will be randomized in a 1:1 ratio to an early intensive lipid-lowering strategy or a guideline-based stepwise intensification strategy.
Eligibility
Sex/Gender
ALL
Age
19 Years to 85 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Minimal Fibrous Cap Thickness | Baseline to 12 months | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in OCT-Derived Lipid Plaque Characteristics | Baseline to 12 months | 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. |
| Change in Lipid Parameters and LDL-C Target Attainment | Baseline to 12 months | 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). |
| Changes in IVUS-Derived Plaque Burden in the IVUS Substudy | Baseline to 12 months | 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. |
Countries
South Korea
Contacts
CONTACTChang-Hwan Yoon, MD, PhD
Outcome results
None listed