Very Early PCSK9 Inhibition for Acute Myocardial Infarction

Official title

Impact of PCSK9 Monoclonal Antibody Very Early Administered in Hospital to Reduce Cardiovascular Events in Acute Myocardial Infarction (IMMEDIATE -MI)

Overview

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.

Interventions

• Drug Standard Lipid-Lowering Therapy
  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.
• Drug Early Intensive Lipid-Lowering Therapy (PCSK9 Inhibitor)
  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.

Primary outcome measures

• Incidence of Major Adverse Cardiovascular Events (MACE) at 12 Months [Time frame: 12 months after index percutaneous coronary intervention (±30 days)]

Secondary outcome measures (6)

• Incidence of Key Secondary Cardiovascular Events [Time frame: 12 months after index PCI (±30 days)]
• Incidence of All-Cause Death [Time frame: 12 months after index PCI (±30 days)]
• Incidence of Non-fatal Myocardial Infarction [Time frame: 12 months after index PCI (±30 days)]
• Incidence of Non-fatal Ischemic Stroke [Time frame: 12 months after index PCI (±30 days)]
• Incidence of Unplanned Ischemia-Driven Revascularization [Time frame: 12 months after index PCI (±30 days)]
• Rehospitalization for Unstable Angina [Time frame: 12 months after index PCI (±30 days)]

Eligibility criteria

Inclusion criteria

• Age ≥18 years.
• Acute myocardial infarction (AMI) onset within 30 days (first hospitalization with a confirmed diagnosis of STEMI or NSTEMI).
• 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.
• At least one angiographically assessed diameter stenosis ≥50% in a non-infarct-related artery (non-IRA) with a reference vessel diameter ≥2.5 mm.
• Able to understand and willing to provide written informed consent, comply with prescribed medical therapy, and complete the required follow-up.

Exclusion criteria

• Cardiogenic shock or severe heart failure (Killip class IV).
• Serum creatinine >150 μmol/L or glomerular filtration rate (GFR) <45 mL/min/1.73 m² calculated by the Cockcroft-Gault equation.
• Known or suspected infective endocarditis or active systemic infection.
• Clinically significant coagulation abnormalities, or anticipated inability to tolerate long-term antiplatelet therapy.
• Pregnant or breastfeeding women, women planning pregnancy within 1 year, or those unwilling to use effective contraception.
• Expected survival <1 year.
• Allergy to iodinated contrast media.
• Prior coronary artery bypass grafting (CABG).
• 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.
• 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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• Zhongshan Hospital, Fudan University — Shanghai

Identifiers

NCT: NCT07208006 · KY2025169

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗