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Acute myocardial infarction (AMI) remains a major cause of morbidity and mortality, particularly in patients with multivessel coronary artery disease. Although primary percutaneous coronary intervention (PCI) has significantly improved short-term outcomes, these patients remain at high risk of recurrent cardiovascular events due to vulnerable non-culprit plaques. Coronary imaging techniques such as intravascular ultrasound (IVUS), optical coherence tomography (OCT), and angiography-derived indices (QFR, RWS) can identify high-risk lesions, but the optimal management strategy is still debated.
Early and intensive lipid-lowering therapy has been shown to stabilize atherosclerotic plaques. PCSK9 monoclonal antibodies, in combination with statins, provide rapid and profound LDL-cholesterol reduction and may enhance plaque stabilization beyond standard therapy. Small imaging studies suggest favorable effects of PCSK9 inhibitors on fibrous cap thickness and lipid burden, but their impact on clinical outcomes in AMI patients with multivessel disease remains uncertain.
This study aims to evaluate whether very early in-hospital administration of a PCSK9 inhibitor, in addition to standard care, can reduce major adverse cardiovascular events (MACE) over 12 months compared with standard lipid-lowering therapy alone. The trial will also explore imaging-based markers of plaque vulnerability and functional indices as secondary endpoints, in order to better understand the mechanisms linking lipid lowering, plaque stabilization, and clinical outcomes.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Standard Lipid-Lowering Therapy | Active Comparator | Participants will receive guideline-recommended lipid-lowering therapy starting with statins. Based on follow-up lipid levels, additional agents such as ezetimibe and PCSK9 inhibitors may be added sequentially, according to routine clinical practice. |
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| Early Intensive Lipid-Lowering Therapy (PCSK9 Inhibitor) | Experimental | Participants will receive early intensive lipid-lowering therapy with a PCSK9 monoclonal antibody initiated during index hospitalization, in addition to statins. Ezetimibe may be added as needed. The PCSK9 inhibitor will be given regardless of baseline lipid levels. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Standard Lipid-Lowering Therapy | Drug | Participants will receive lipid-lowering therapy according to current clinical guidelines. Treatment will be initiated with statins. Based on follow-up lipid levels, ezetimibe may be added, and PCSK9 inhibitor therapy may be considered if LDL-C goals are not met. |
| Measure | Description | Time Frame |
|---|---|---|
| Incidence of Major Adverse Cardiovascular Events (MACE) at 12 Months | MACE is defined as a composite endpoint including all-cause death, non-fatal myocardial infarction, stroke, unplanned ischemia-driven revascularization, and rehospitalization for unstable angina. The occurrence of the first event from this composite will be recorded for each participant. | 12 months after index percutaneous coronary intervention (±30 days) |
| Measure | Description | Time Frame |
|---|---|---|
| Incidence of Key Secondary Cardiovascular Events | Composite of cardiovascular death, non-fatal myocardial infarction, stroke, and unplanned ischemia-driven revascularization. | 12 months after index PCI (±30 days) |
| Incidence of All-Cause Death |
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Inclusion Criteria
Exclusion Criteria
10.1 Non-IRA lesion with visually estimated diameter stenosis >90% and TIMI flow ≤2; 10.2 Complex coronary artery disease requiring CABG; 10.3 Angiography unable to clearly identify the infarct-related artery or non-infarct-related arteries.
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Wei Gao, PhD | Contact | +8613661959824 | gao.wei1@zs-hospital.sh.cn |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Zhongshan Hospital, Fudan University | Recruiting | Shanghai | Shanghai Municipality | 200032 | China |
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| Early Intensive Lipid-Lowering Therapy (PCSK9 Inhibitor) | Drug | Participants will receive early intensive lipid-lowering therapy with a PCSK9 monoclonal antibody, initiated during the index hospitalization, in addition to statins. Ezetimibe may be added if clinically indicated. The PCSK9 inhibitor will be administered regardless of baseline lipid levels. |
|
Death from cardiovascular causes, non-cardiovascular causes, or unknown causes.
| 12 months after index PCI (±30 days) |
| Incidence of Non-fatal Myocardial Infarction | Defined according to SCAI criteria for peri-procedural MI and spontaneous MI related to culprit or non-culprit vessels. | 12 months after index PCI (±30 days) |
| Incidence of Non-fatal Ischemic Stroke | Stroke confirmed by clinical diagnosis and imaging, excluding hemorrhagic stroke. | 12 months after index PCI (±30 days) |
| Incidence of Unplanned Ischemia-Driven Revascularization | Repeat PCI or CABG driven by ischemic symptoms or objective evidence of ischemia, involving culprit or non-culprit vessels. | 12 months after index PCI (±30 days) |
| Rehospitalization for Unstable Angina | Hospital admission due to recurrent chest pain confirmed as unstable angina requiring medical management. | 12 months after index PCI (±30 days) |