Comparison of Neointimal Coverage Between Zotarolimus Eluting Stent and Everolimus Eluting Stent
Condition: Coronary Artery Disease
MeSH terms: Coronary Artery Disease
Study type: Interventional
Phase: Phase 4

Summary: 
      Stent thrombosis is an important issue in drug eluting stents. Incomplete endothelial
      coverage and neointimal coverage over strut after drug eluting stent (DES) implantation could
      be a possible cause of stent thrombosis. Therefore, theoretically dual antiplatelet therapy
      should be continued to prevent the stent thrombosis until complete reendothelialization. But,
      detection of endothelial coverage over stent is not possible with the available intravascular
      devices in clinical practice. Among currently available intravascular devices, intravascular
      optical coherence tomography (OCT) could give a more clear identification for a thin layer of
      neointima with high-resolution (10-20 μm) compared to intravascular ultrasound (100-150 μm).
      Previous OCT studies showed the significant different pattern of neointimal coverage between
      bare metal stent (BMS) and DES. In the investigators' experience, there were also some
      differences in neointimal coverage among the DESs, especially zotarolimus eluting stent
      (ZES). ZES has been known to be associated with significantly more neointimal coverage than
      SES at 8 months intravascular ultrasound (IVUS). Both everolimus eluting stent (EES) and ZES
      resolute were recently introduced. The efficacy to suppress the neointimal growth for ZES
      resolute and EES might be improved, but safety for neointimal coverage needs to evaluate in
      human coronary artery. Therefore, this study will investigate the pattern of neointimal
      coverage over stent in ZES resolute and EES at 9 months after stent implantation.
    

Detailed description: 
      Recent autopsy study showed the most important histological and morphometric predictors of
      stent thrombosis were endothelial coverage and the ratio of uncovered to total strut after
      drug eluting stent (DES) implantation. Although there have been some controversies,
      incomplete stent apposition might be possible cause of very late stent thrombosis after DES
      implantation. Therefore, theoretically dual antiplatelet therapy should be continued to
      prevent the stent thrombosis until complete reendothelialization. But, detection of
      endothelial coverage over stent are no possible with available intravascular devices in
      clinical practice. Among currently available intravascular devices, intravascular optical
      coherence tomography (OCT) could give a more clear identification for a thin layer of NIH and
      malapposition with high-resolution (10 -20 μm) compared to intravascular ultrasound (100-150
      μm). Previous OCT studies showed the significant different pattern of neointimal coverage
      between bare metal stent (BMS) and DES. In our experience, there was also some differences in
      neointimal coverage among the DESs, especially zotarolimus eluting stent (ZES). ZES have been
      known to be associated with significantly more neointimal coverage than SES at 8 months
      intravascular ultrasound (IVUS). This finding might be related with strut thickness and drug
      elution property. In our data, neointima was covered at 99.7% of stent strut in ZES, but
      93.2% in sirolimus eluting stent (SES) at 9 month follow OCT. This difference was more
      distinct in patients with acute myocardial infarction (99.3% in ZES vs.79.9% in SES).

      Both everolimus eluting stent (EES) was recently introduced and ZES resolute also will be
      available in the near future in Korea. Previous phosphorylcholine polymer was replaced with
      new, proprietary polymer which can provide extended elution kinetics in ZES resolute.
      Therefore, efficacy to suppress the neointimal growth might be improved but, safety for
      neointimal coverage needs to evaluate in human coronary artery. Both new DESs are cobalt
      chromium stent with thin stent strut and reported similar efficacy for suppressing the
      neointima growth. Also, endothelial coverage over stent strut occurred earlier compared to
      previous DESs (SES or PES) in animal experiments. But, there has been no data for neointimal
      coverage and malapposition of ZES resolute and EES using OCT in human coronary artery.

      Recent paper according to Kubo et al reported that serial OCT examinations demonstrated
      markedly different vascular response up to 9 months after SES implantation between unstable
      angina and stable angina patients. These findings implied that initial native vessel status,
      which covered with stent, might be important and related with neointimal coverage and
      malapposition. But, there is little data evaluated the relationship between initial lesion
      status and neointimal coverage or late malapposition with OCT.

      Therefore, this study investigates: 1) the relationship of the initial lesion and neointimal
      coverage or late malapposition and 2) the neointimal coverage and malapposition at 9 month
      after ZES resolute and EES implantation and 3) compare them between ZES resolute and EES at 9
      months after stent implantation.

      Study Objectives:

      This study is a prospective open labeled randomized study to compare the neointimal coverage
      of ZES resolute (Endeavor® resolute) and EES (Xience®) in 9 month after stent implantation by
      OCT.

        1. Primary end point:

             -  The primary endpoint is to compare the neointimal coverage of ZES resolute
                (Endeavor® resolute) and EES (Xience®) at 9 months after stent implantation by OCT.

        2. Secondary end points:

             -  To investigate the relationship between initial lesion and neointimal coverage and
                malapposition at 9 months, and

             -  To compare of neointimal growth between ZES resolute and EES at 9 months and to
                compare the difference in early and late malapposition between ZES resolute and EES
                at 9 months.
    

Intervention name(s): Zotarolimus eluting stent (Endeavor resoulte - ZES resolute); Everolimus eluting stent (Xience - EES)
Intervention type(s): Device; Device
Intervention description(s): Zotarolimus eluting stent (ZES); Everolimus eluting stent (EES)
Intervention MeSH terms: Everolimus
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment