Nouveaux concepts en cardiologie interventionnelle coronaire.

Nouveaux concepts en cardiologie
interventionnelle coronaire.
P.Barragan.Ollioules
PARIS GRCI : vendredi 3 décembre 2010
NEW CONCEPTS IN PCI ?
Stent
Polymer
Drug
DRUG
Indications 2007 des DES en PACA
B.Valeix: Observatoire régional
WHICH DRUG ?
Limus ?
Paclitaxel ?
Others ?
WHICH DRUG ?
Comparison :
Taxus Element vs Promus Element
POLYMER
Comparison of DES Release Profiles
ENDEAVOUR
100
CYPHER
XIENCE /PROMUS
Percentage
80
60
40
20
0
TAXUS
0
10
20
30
40
50
60
70
Time (day)
80
90
100
110
120
Biocompatibility
Styrene-IsobutyleneStyrene: TAXUS
•  Durable C-C backbone
•  No reactive groups to hydrolyze and less prone to
oxidative reaction
•  RESULT: Good biocompatibility
Phosphoryl-choline
(PC): ENDEAVOR
•  Durable C-C backbone
•  Many reactive groups – hydrolysis and oxidation
possible on the side chain
•  RESULT: Good biocompatibility
Fluorinated
Copolymer:
XIENCE/PROMUS
•  Durable C-C backbone
•  Covalent C-F bonds result in stability - noreactivity to hydrolysis or oxidation in-vivo
•  RESULT: Good biocompatibility
PEVA-PBMA:
CYPHER®
•  Durable C-C backbone
•  PBMA – stable; oxidation unlikely and hydrolysis
less likely
•  PEVA – EVA is susceptible to hydrolysis in vivo and
the release of acetic acid
•  RESULT: Questionable biocompatibility
Percentage of struts showing granuloma formation and percentage of
granulomas showing >=10 eosinophils per high-powered (x40 objective)
field
Wilson, G. J. et al. Circulation 2009;120:141-149
Mechanical Coating Integrity ?
TAXUS EXPRESS STENT
Mechanical Coating Integrity
ENDEAVOR
?
Endeavor and Resolute Stents
STENT
Endeavor™ Stent
Resolute™
Stent
Driver™ Stent
Driver Stent
POLYMER
Phosphorylcholine
(PC)
DRUG & DOSE
Zotarolimus
10µg/mm stent
length
ELUTION
RATES
75% in 2 days,
100% in 14 days
BioLinx™
Durable Co-polymer
blend
Zotarolimus
10µg/mm stent
length
~70% in 30 days,
Remainder in 180
days
STENT
Future of the metallic structure?
1/ Switch to Drug Eluting Balloon ?
2/ Very Thinner Struts ?
3/ Bioabsorbable Scaffold ?
Future of the metallic structure?
1/ Switch to Drug Eluting Balloon ?
2/ Very Thinner Struts ?
3/ Bioabsorbable Scaffold ?
Drug Eluting Balloons
(B-Braun,Biotronik...)
The current indications :
-In Stent Restenosis +++
-Small Vessel Disease ?
- Bifurcations ?
Drug Eluting Balloon + Stent
PEPCAD III :
Failure versus Cypher Stent
PIONEER Trial :
New trial (Blue Medical)
Future of the metallic structure?
1/ Switch to Drug Eluting Balloon ?
2/ Very Thinner Struts ?
3/ Bioabsorbable Scaffold ?
Low Strut and Polymer Thickness
Cypher Select +
BIOMATRIX
Abluminal Polymer: Abluminal Polymer:
13.7 µm
16.6 µm
RESOLUTE
TAXUS Element
Abluminal Polymer:
6.2 µm
Abluminal Polymer:
14.9 µm
Strut Thickness:
Strut Thickness:
Strut Thickness:
Strut Thickness:
140 µm
119 µm
91 µm
81 µm
PROMUS Element
XIENCE PRIME
Abluminal Polymer: Abluminal Polymer:
6.6 µm
7.8 µm
Strut Thickness:
Strut Thickness:
81 µm
81 µm
Stent fracture
Xience/Promus 28 x 2.5
Stent fracture: a fatigue phenomenon
Nakazawa et al. JACC 54(21) 2009
Optimal Stent Mechanical Properties
Poncin et al, Stent yubing, ASM Conference Sept 2003
Optimal Stent Mechanical Properties
O’Brien BJ et al, Biomaterial 31: 3755-61,2010
Limits of standard metal used for stents
Current stent grain sizes are in the range of 20-25µm for
316-L and 30µm for Co-Cr
Conventional techniques to reduce the grain size(cold work)
usually make the material too brittle
Murphy et al.Ann Biomed Eng ,31:686-91,2003
Even the best super alloys have their
intrinsic limits
BurgErmeister et al, USPTO/US 2006/0020325
Nano-structuring using Cold Spray:
Challenge=increase ductility further(10-20%)
R.Mongrain ,McGill University,Montreal
Future of the metallic structure?
1/ Switch to Drug Eluting Balloon ?
2/ Very Thinner Struts ?
3/ Bioabsorbable Scaffold ?
Bioresorbable Polymer: ABSORB
• 
• 
• 
• 
• 
Drug/polymer matrix
• 
Everolimus/PDLLA Matrix
Coating
Thin coating layer
Amorphous (non-crystalline)
1:1 ratio of Everolimus/PLA
matrix
Conformal Coating, 2-4 µm
thick
Controlled drug release
Polymer backbone
• 
• 
• 
• 
PLLA Backbone
Highly crystalline
Provides device integrity
Processed for increased radial
strength
ABSORB 6, 12, 24 and 36-Month
Hierarchical
Ischemia Driven
MACE
Cardiac Death
MI
Q-Wave MI
Non Q-Wave
MI
Ischemia Driven
TLR
by PCI
by CABG
6 Months
30 Patients
12 Months
29
Patients**
24 Months
28 Patients**
1 (3.3%)*
1 (3.4%)*
1 (3.6%)*
0 (0.0%)
0 (0.0%)
0 (0.0%)
1 (3.3%)*
1 (3.4%)*
1 (3.6%)*
0 (0.0%)
0 (0.0%)
0 (0.0%)
1 (3.3%)*
1 (3.4%)*
1 (3.6%)*
0 (0.0%)
0 (0.0%)
0 (0.0%)
0 (0.0%)
0 (0.0%)
0 (0.0%)
0 (0.0%)
0 (0.0%)
0 (0.0%)
0 (0.0%)
0 (0.0%)
0 (0.0%)
No new MACE between 6 and 36 months
36
Months
28
Patients*
*
1
(3.6%)*
0 (0.0%)
1
(3.6%)*
0 (0.0%)
1
(3.6%)*
In ‘stent’ RVD
(mm)
Post PCI
N=17
6 Month
N=17
2 Year
N=17
2.71
2.48
2.40
Serruys PW, et al., Lancet 2009; 373: 897-910.
BVS Device Optimization
Objectives
•  More uniform strut distribution
•  More even support of arterial wall
•  Higher radial strength
Cohort A
•  Lower late ‘stent’ area loss
•  Storage at room temperature
•  Improved device retention
Cohort B
Photos taken by and on file at Abbott Vascular.
•  Unchanged:
–  Material, coating and backbone
–  Strut thickness
–  Drug release profile
–  Total degradation Time
ART01 DESIGN
At 30 Days
At 90 Days
Antoine Lafont TCT 2010
Antoine Lafont TCT 2010
New DES :
BMS
TAXUS LIBERTE
BIOMATRIX FLEX
XIENCE V
CYPHER
*
*
*
ISAR TEST 4
LESSON 1
LEADERS
COMPARE
DOYLE STETTLER
ROUKOZ
My Prophecie : The « ultimate »
stent will be ...
1/Metallic as thin as possible (<50 µ).
2/Biocompatible and bioabsorbable polymer .
2/Drug coating as biocompatible as possible
*with an exclusive inhibition of smooth muscle
cell migration and proliferation
*Allowing an optimal re-endothelialization !