Healthy Endothelial Accelerated Lining Inhibits Neointimal Growth
Condition: Coronary Artery Disease; Coronary Artery Stenosis
MeSH terms: Coronary Artery Disease; Coronary Stenosis
Study type: Interventional
Phase: Phase 4

Summary: 
      This is a multi-center, prospective, non-randomized study. Approximately 90 patients from up
      to 16 centers will be entered in the study. Patients will be followed clinically for up to 5
      years post-procedure. All patients will have a repeat angiography at 6 months follow-up.

      The primary objective of this study is to evaluate the safety and effectiveness of the Genous
      Bio-engineered R stentTM in conjunction with optimal statin therapy (80mg of atorvastatin),
      in the treatment of elective patients with up to two de novo native coronary artery lesions.
      The Genous stent received CE mark for the intended indication in August 2005
    

Detailed description: 
      Currently available coronary stents are prone to thrombosis and restenosis. It is believed
      that the accelerated re-establishment of a functional endothelial layer on damaged stented
      vascular segments may help to prevent potentially serious complications by providing a
      barrier to circulating cytokines, and by the ability of endothelial cells to produce
      substances that passivate the underlying smooth muscle cell layer.

      By recruiting the patient's own EPCs to the site of vascular injury (e.g. the site of a
      coronary stent implant), an acceleration of the normal endothelialization process would
      occur. It is theorized that the rapid establishment of a functioning endothelial layer may
      promote the transformation of the injured site to a healthy state. For example, in the case
      of coronary stent implantation, rapid re-endothelialization may reduce inflammation,
      thrombosis and potentially eliminate restenosis.

      The influences of EPC recruitment and reendothelialization on restenosis range from the
      effects on the vascular repair response, to the prevention of platelet aggregation and
      activation, angiogenesis, and enhancement of vasomotor response. Recently it has been shown
      that the integrity and functional activity of the endothelial monolayer play a crucial role
      in the prevention of atherosclerosis. However, risk factors for coronary artery disease such
      as age, hypertension, hypercholesterolemia, and diabetes reduce the number and functional
      activity of these circulating EPCs, thus limiting the regenerative capacity. The impairment
      of stem cells by risk factors in CAD patients may contribute to the limited regenerative
      capacity of diseased endothelium, as well as to atherogenesis and atherosclerotic disease
      progression. Therefore, relating the number and function of circulating EPCs to the
      functional outcome of stent technology is crucial to identify a beneficial effect on in-stent
      restenosis formation and vascular (dys) function.

      The HEALING FIM and HEALING II clinical studies sought to define the safety and efficacy of a
      stent designed to sequester circulating endothelial progenitor cells to the luminal surface
      of the stent struts by an anti-CD34 antibody coating, thereby promoting reendothelialization
      of the coronary stent and the vascular healing response following stent deployment. Enhanced
      vascular healing will reinstate vascular integrity, prevent platelet aggregation and
      sub-acute in-stent thrombosis, reinstate vasoreactivity and inhibit restenosis formation. In
      the HEALING II study, a correlation was found between EPC levels and angiographic/IVUS
      outcomes in patients receiving the Genous stent. Patients with normal EPC titers had
      significantly less in-stent late loss compared to those with low EPCs (0.53 vs 1.02mm). This
      is consistent with the results from drug eluting stent trials, thereby establishing proof of
      concept of the EPC capturing technology, provided adequate EPC target cell population is
      available.

      There are several animal studies demonstrating that statin therapy was associated with a 2.5
      to 3 fold increase of circulating EPCs leading to accelerated reendothelialization, vascular
      repair and improved angiogenesis. In addition, Dimmeler and co-workers found similar results
      in a small cohort of cardiovascular patients receiving atorvastatin therapy (n=7, Circulation
      2001), suggesting an angiotrophic effect of atorvastatin therapy in addition to its
      previously defined pleiotrophic properties. Similarly, Drexler and co-workers described
      similar EPC recruiting properties of simvastatin in CAD patients unrelated to/ irrespective
      of LDL reduction (n=10, Circulation 2005).

      The current study seeks to confirm the safety and optimize the effectiveness of the EPC
      capture technology (Genous Bio-engineered R stent) by incorporating a high dose statin
      therapy, specifically atorvastatin 80mg, for at least two weeks prior to the index procedure.
    

Intervention name(s): Coronary stent implantation
Intervention type(s): Device
Intervention description(s): Percutaneous Coronary Intervention
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Percutaneous Transluminal Coronary Angioplasty; Stent implantation