Very Early PCSK9 Inhibition for Acute Myocardial Infarction

Fudan University

Status: Enrolling

Conditions: Acute Myocardial Infarction (AMI)

Treatments: Drug: Standard Lipid-Lowering Therapy; Drug: Early Intensive Lipid-Lowering Therapy (PCSK9 Inhibitor)

Study type: Interventional

Funder types: Other

Identifiers

NCT07208006

KY2025169

Details and patient eligibility

About

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.

Enrollment: 1,518 estimated patients

Sex: All

Ages: 18 to 100 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria

1. Age ≥18 years.
2. Acute myocardial infarction (AMI) onset within 30 days (first hospitalization with a confirmed diagnosis of STEMI or NSTEMI).
3. Multivessel coronary artery disease; successful percutaneous coronary intervention (PCI) of the culprit lesion in the infarct-related artery (IRA), including stent implantation and/or balloon angioplasty and/or thrombus aspiration.
4. At least one angiographically assessed diameter stenosis ≥50% in a non-infarct-related artery (non-IRA) with a reference vessel diameter ≥2.5 mm.
5. Able to understand and willing to provide written informed consent, comply with prescribed medical therapy, and complete the required follow-up.

Exclusion Criteria

1. Cardiogenic shock or severe heart failure (Killip class IV).
2. Serum creatinine >150 μmol/L or glomerular filtration rate (GFR) <45 mL/min/1.73 m² calculated by the Cockcroft-Gault equation.
3. Known or suspected infective endocarditis or active systemic infection.
4. Clinically significant coagulation abnormalities, or anticipated inability to tolerate long-term antiplatelet therapy.
5. Pregnant or breastfeeding women, women planning pregnancy within 1 year, or those unwilling to use effective contraception.
6. Expected survival <1 year.
7. Allergy to iodinated contrast media.
8. Prior coronary artery bypass grafting (CABG).
9. Participation in another clinical trial within 3 months before enrollment, or current participation in another drug/device clinical trial without having reached its primary endpoint.
10. Coronary angiography-based 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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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1,518 participants in 2 patient groups

Standard Lipid-Lowering Therapy

Active Comparator group

Description:

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.

Treatment:

Drug: Standard Lipid-Lowering Therapy

Early Intensive Lipid-Lowering Therapy (PCSK9 Inhibitor)

Experimental group

Description:

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.

Treatment:

Drug: Early Intensive Lipid-Lowering Therapy (PCSK9 Inhibitor)