Effect of Evolocumab on Coronary Plaque Characteristics
Condition: Coronary Artery Disease
MeSH terms: Coronary Artery Disease; Myocardial Ischemia; Coronary Disease
Intervention: Evolocumab Injections
Intervention description: Administered on day 1 (the day of the first treatment) and through week 26 with a personal injector or prefilled auto injector/pens.
Intervention MeSH terms: Evolocumab
Phase: Phase 4
Study type: Interventional
Primary purpose: Basic Science
Intervention model: Single Group Assignment
Intervention model description: The study team will screen patients scheduled for elective PCI, who are receiving statin therapy for at least 4 weeks with acceptable LDL-C levels. Patients with non-obstructive lesion (30-50% stenosis) by angiography and lipid-rich plaque with lipid arc >90° and minimal fibrous cap thickness ≤ 120 µm detected by OCT will comprise the final study population. Serial NIRS/IVUS and OCT imaging will be performed in a non-target lesions, first during PCI and subsequently after 26 weeks.
Masking: None (Open Label)
Enrollment: 137.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Coronary Artery Disease; Coronary Plaque; Optical Coherence Tomography; Near-Infrared Spectroscopy; Evolocumab; Statin

Summary:

      The aim of the study is to assess the effect of evolocumab on coronary plaque morphology
      using intravascular imaging and gene expression analysis of peripheral blood mononuclear
      cells (PBMC) in patients with stable CAD on maximally tolerated statin therapy. The study
      combines multi-modality intravascular imaging approaches and transcriptomic based machine
      learning algorithms to uncover molecular mechanisms responsible for the beneficial changes in
      atherosclerotic lesions of patients treated with evolocumab. The primary end-points are the
      changes from baseline to follow-up in (1) the minimal fibrous cap thickness (FCT) assessed by
      optical coherence tomography (OCT) and (2) maxLCBI4mm assessed by near-infrared spectroscopy
      (NIRS) after 26 weeks of evolocumab. The secondary endpoints are the changes in (1) the
      maximal lipid arc, lipid length, lipid volume index, macrophage accumulation and
      calcification by OCT; (2) PAV and TAV defined by intravascular ultrasound (IVUS) and (3)
      Changes in PBMC gene expression.
    

Eligibility criteria:

        Inclusion criteria:

          -  Men or women aged 18 years or older at screening who signed written Informed Consent

          -  Patients with coronary artery disease undergoing cardiac catheterization and PCI for a
             target lesion and also have a non-obstructive lesion (30-50% stenosis) identified by
             angiography

          -  Patients who are not candidates for PCI or CABG currently or over the next 12 months,
             in the opinion of the investigator

          -  Patients treated with statins for at least 4 weeks with LDL-C level ≥ 80 mg/dL for
             low- or moderate -intensity statin use and ≥ 60 mg/dL for high-dose statin. Patients
             with history of statin intolerance and LDL-C ≥ 100 mg/dL.

          -  Angiographic criteria: 30-50% reduction of lumen diameter in addition to the target
             lesion accessible by the OCT catheter. The target segment should not have a history of
             percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG),
             and may not be a bypass graft.

          -  OCT criteria: target segment should have a lipid-rich plaque with lipid arc >90° and
             fibrous cap thickness ≤120 µm.

          -  Women of childbearing potential must agree to be on an acceptable method of birth
             control/contraceptive

        Exclusion criteria:

          -  Patients who have acute myocardial infarction (Q wave or non-Q wave with CK-MB > 5
             times above the upper normal (31.5 ng/ml) within 72 hours)

          -  Patients who are in cardiogenic shock

          -  Patients with left main disease, in-stent restenotic lesions or patients requiring
             coronary artery bypass graft surgery

          -  Patients with elevated CK-MB (>6.3 ng/ml) or Tnl (>0.5 ng/ml)

          -  Patients with platelet count < 100,000 cell/mm3

          -  Patients who have co-morbidity which reduces life expectancy to one year

          -  Patients who are currently participating in another investigational drug/device study

          -  Patients with liver disease

          -  Patient with creatinine > 2.0 mg/dL

          -  Pregnant women and women of childbearing potential who intend to have children during
             the duration of the trial

          -  Patients having undergone heart transplantation, or those that may undergo heart
             transplantation during the study period

          -  Patients with active autoimmune disease