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.
Age 19 to 85 years.
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.
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.
Provision of voluntary written informed consent after receiving sufficient information regarding the study objectives, procedures, and follow-up plan.
Severe hepatic dysfunction, defined as AST or ALT >3 times the upper limit of normal.
CK >5 times the upper limit of normal or suspected clinically significant myopathy.
Severe renal impairment, defined as eGFR <30 mL/min/1.73 m².
Severe hypersensitivity to or contraindication to statins, ezetimibe, or inclisiran.
Parallel
Inclisiran
DrugInclisiran 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).
Atorvastatin or Rosuvastatin
DrugHigh-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.
Ezetimibe
DrugEzetimibe 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.
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.
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.
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).
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.
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.
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Seoul National University Bundang Hospital
Lead sponsor
Dotter Co., Ltd.
Collaborator
Novartis Korea Ltd.
Collaborator
Hanmi Pharmaceutical co., ltd.
Collaborator
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