Z-SEA-SIDE: Sirolimus Versus Everolimus Versus Zotarolimus-eluting Stent Assessment in Bifurcated Lesions and Clinical SIgnificance of Residual siDE-branch Stenosis
Condition: Coronary Artery Disease; Coronary Stenosis
MeSH terms: Coronary Artery Disease; Coronary Stenosis; Constriction, Pathologic
Study type: Interventional
Phase: Phase 4

Summary: 
      BACKGROUND:

      Bifurcated lesions are a challenging subset in percutaneous coronary interventions (PCI). The
      selection of the type of drug-eluting stents (DES) and the technique for stent implantation
      have not been clarified. The side-branch (SB) is emerging as critical point, accounting for
      more than a third of the significant restenosis in the DES era. A series of data supports the
      adoption of a conservative strategy: stenting the main vessel (MV) only and reserving a
      conservative approach on the SB. Yet, the clinical relevance in terms of inducible ischemia
      of sub-optimal angiographic result has not been clarified.

      AIMS OF THE STUDY:

      The aims of the present study are:

        1. to compare in a prospective study the acute 3D angiographic results and the late
           clinical outcome of Sirolimus-eluting (SES) vs Everolimus-eluting (EES) vs Zotarolimus
           eluting stent (ZES) obtained using a provisional TAP-stenting technique.

        2. to prospectively assess the clinical relevance (inducible ischemia) of suboptimal
           angiographic result in the SB after stenting.

      METHODS TO BE APPLIED:

      75 consecutive patients with bifurcated lesions undergoing PCI with the provisional
      T-and-small-protruding (TAP) technique with ZES implantation will be enrolled. Procedural and
      post-PCI details will be prospectively recorded. The subgroup of patients in which complete
      revascularization has been achieved will enter a systematic assessment of inducible ischemia
      by early and late exercise tests.

      Off line 3D quantitative coronary angiography (QCA) assessment will be performed and used to
      divide the study population in 2 groups according to the SB residual stenosis:

        -  Group O (optimal SB angiographic result): post-PCI SB area stenosis<50%

        -  Group S (sub-optimal SB angiographic result): post-PCI SB area stenosis>50%.

      For the comparison among SES and EES, data will be obtained from the randomized trial
      SEA-SIDE (NCT00697372).

      PRIMARY STUDY END-POINTS.

        1. COMPARISON BETWEEN ZES, SES AND EES:

           SB acute angiographic result; SB trouble; target bifurcation failure.

        2. SB-RELATED ISCHAEMIA of Group O vs Group S in patients with complete revascularization:
           inducible ischemia at the early exercise test or occurrence of early spontaneous
           ischemia related to the SB.
    

Detailed description: 
      Bifurcated lesions are challenging target lesions in percutaneous coronary interventions
      (PCI) which may specifically benefit from the usage of drug-eluting stents (DES). However,
      the selection of the type of DES and the technique for DES implantation have not been
      clarified. In spite of the technique adopted, the side-branch (SB) is emerging as critical
      point, accounting for more than a third of the significant restenosis in the DES era. A
      series of data supports the adoption of a conservative strategy: stenting the main vessel
      (MV) only and reserving a conservative approach on the SB as this is not associated with
      worse outcome compared to more complex stenting strategies. Yet, the clinical relevance in
      terms of inducible ischemia of sub-optimal angiographic result has not been clarified.

      AIMS OF THE STUDY:

      The aims of the present study are:

        1. to compare in a prospective study the acute 3D angiographic results (as a measure of the
           impact of stent design) and the late clinical outcome of Sirolimus-eluting (SES) vs
           Everolimus-eluting (EES) vs Zotarolimus-eluting stent (ZES) obtained using a provisional
           T-and-small-protruding (TAP) approach to treat bifurcated lesions.

        2. to prospectively assess the clinical relevance (in terms of inducible ischemia) of
           suboptimal angiographic result in the SB of bifurcated lesions treated by stenting.

      METHODS TO BE APPLIED:

      75 consecutive patients with bifurcated lesions undergoing PCI with the provisional
      TAP-stenting technique with ZES implantation will be enrolled. Procedural details, post-PCI
      cardiac enzyme release, clinical outcome up to 1 year will be prospectively recorded. After
      the procedure, the subgroup of patients in which complete revascularization has been achieved
      (no untreated stenosis >50% in any other vessel, no residual stenosis >50% in any other
      treated vessel), will enter a systematic assessment of inducible ischemia by early (<8 days)
      and late (6-month) exercise tests.

      Off line 3D quantitative coronary angiography (QCA) assessment will be performed and used to
      divide the study population in 2 groups according to the SB residual stenosis: Group O
      (optimal SB angiographic result): post-PCI SB area stenosis<50% and Group S (sub-optimal SB
      angiographic result): post-PCI SB area stenosis>50%.

      For the comparison among SES and EES, data will be obtained from the randomized trial
      SEA-SIDE (NCT00697372).

      PRIMARY STUDY END-POINTS.

      1.

      COMPARISON BETWEEN ZES, SES AND EES:

        -  "SB acute angiographic result": comparison of the 3DQCA-estimated MLD and MLA in the SB.

        -  "SB trouble": composite of: 1. occurrence of SB TIMI flow <3 after MV stenting
           throughout the procedure; 2. need of guidewire(s) different from BMW to re-wire SB after
           MV stenting; 3. failure to re-wire the SB after MV stenting; 4. failure to dilate the SB
           after MV stenting and SB re-wiring.

        -  target bifurcation failure (TBF) defined as target bifurcation-related major adverse
           coronary events (MACE) or target bifurcation angiographic failure.

           2. SB-RELATED ISCHAEMIA of Group O vs Group S in patients with complete
           revascularization: inducible ischemia (diagnostic ST-segment changes) at the early (<8
           days) exercise test or occurrence of early (<12 weeks) spontaneous ischemia related to
           the SB (any ischemic episode requiring unplanned coronary angiography with documentation
           of main vessel patency).
    

Intervention name(s): Sirolimus eluting stent; Everolimus eluting stent; Zotarolimus eluting stent
Intervention type(s): Device; Device; Device
Intervention description(s): Implantation of Sirolimus eluting stent; Implantation of Everolimus eluting stent; Implantation of Zotarolimus eluting stent
Other intervention name(s): Cypher stent - Cordis (Johnson&Johnson Company); Xience stent - Abbot company; Endeavor Resolute stent - Medtronic company
Intervention MeSH terms: Sirolimus; Everolimus
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Angioplasty, Transluminal, Percutaneous Coronary; Drug-Eluting Stents