Drug Eluting Stents Using Bioresorbable Polymers are the Best Clinical Choice Juan F. Granada, MD Executive Director and Chief Scientific Officer Skirball Research Center Cardiovascular Research Foundation Columbia University Medical Center, New York TCT at SOLACI-CACI 2014,Thursday April 24rd
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Drug Eluting Stents Using Bioresorbable Polymers are the ... · Technology Drug Drug Dose Absorption Time Polymer Polymer Thickness Absorption Time Stent Material Stent Thickness
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Drug Eluting Stents Using Bioresorbable Polymers are
the Best Clinical Choice
Juan F. Granada, MD Executive Director and Chief Scientific Officer
Haude M. TCT2012, 15. Haude M. JACC Cardiovasc Interv. 2013;6:334-343, 16. Lemos P. TCT2012, 17. Stefanini GG,Heart. 2013
Polymer Type, Distribution and
Loading in Different DES Designs
Commercially Available DES Systems Strut and Coating Thickness In Perspective
Xience CoCr-
EES
Promus PtCr-
EES
Biomatrix
316L-BES Nobori
316L-BES BVS
PLLA-EES SYNERGY PtCr-EES
Resolute
CoNi-ZES
Durable
Polymer Coated Stents
Bioabsorbable
Polymer Coated Stents
Bioabsorbable
Stent
Strut Thickness
81µm 89µm 120µm 125µm 74µm 150µm
Polymer Coating Conformable
7-8µm / side
Conformable
6µm / side
Abluminal
11µm
Abluminal
20µm
Abluminal
4µm
Conformable
3µm / side
Presented by Yen Lane Chen, PhD at EuroPCR 2012; World J Cardiol 2011 March 26; 3(3): 84-92; Garg, S, J Am Coll Cardiol. 2010;56(10s1):S43-S78. doi:10.1016. Presented by Stephen Windecker, MD, TCT2012.
Polymer: PLGA Absorption Time: 3-4 mo
% R
eco
very
Time (months)
Drug Release-Polymer Absorption Profiles
SYNERGY
Everolimus
PLGA
Nobori and Biomatrix Flex
% R
eco
very
Polymer: PLA Absorption Time: >9 mo
BA9
PLA
Orsiro
% R
eco
very
Time (months)
Polymer: PLLA Absorption Time: >12 mo
Time (months)
Sirolimus
PLLA
(molecular
weight
change)
% R
eco
very
Time (months)
Absorb BVS
Scaffold: PLLA Polymer: PDLLA
Absorption Time: >2 yrs
Everolimus
PLLA
DES Using Bioresorbable Polymers
0,7
0,28
0,6
0,15
1,3
0,3
0,62
0,31
1,4
0,7
1,24
0,53
2,14
0,54
1,1
0,3
0
0,5
1
1,5
2
2,5
Stent Thrombosis: Latest Generation DES 1 vs. 3 Year Thrombotic Events
PLATINUM Presented by Ian Meredith AM, MBBS, PhD at ACC 2013; SPIRIT III presented by Gregg Stone at TCT 2001; SPIRIT IV
presented by Gregg Stone, MD at TCT 2011; COMPARE Presented by Peter Smits, MD at TCT 2011; Resolute All-Comers presented by
Stephan Windecker at PCR 2012; Resolute International presented by F-J. Neumann at TCT2012; LEADERS Presented by Patrick Serruys,
MD at TCT 2010
PROMUS Element
Xience V
Resolute
A A B C D E E F
ARC ST (Def/Prob)
3-Year Cumulative
VLST (Def/Prob)
From 1 to 3 Years
A A B C D E E F
A: PLATINUM Trial
B: SPIRIT III Trial
C: SPIRIT IV Trial
D: COMPARE Trial
E: RESOLUTE All-Comers Trial
F: RESOLUTE International
<1-YEAR STENT THROMBOSIS
• Non-device related variables
• Patient, lesion and technique
• Device thrombogenicity
• Polymer-drug
• Stent design
>1-YEAR STENT THROMBOSIS
• Vascular response to implant
• Acquired malapposition
• Neoatherosclerosis
• Delayed strut healing
• DATP compliance
Early Stent Thrombogenicity Non-Absorbable vs. Absorbable Polymer
Conformal distribution of non-
absorbable polymer and drug
Luminal Side Luminal Side
Abluminal distribution of
absorbable polymer and drug
“+” denotes biological activity of drug eluting polymer
*Technology dependent
+ + +
+
+
+
+ + +
+
+ +
+ + +
+
+
Abluminal Side Abluminal Side
4 to 12 month polymer
absorption time*
According to the polymer-drug absorption time*, the net effect
on healing may be comparable between bioresorbable and
durable polymers within the first 6 to 9 months
Early Stent Thrombogenicity of EES Durable PVDF Polymer + Drug vs. CoCr Control
Kolandaivelu K, Circulation 2011, 123:1400-1409
Comparable degree of
thrombogenicity of PVDF-coated
EES vs. CoCr metal only controls
Late Stent Thrombogenicity Non-Absorbable vs. Absorbable Polymer
Conformal distribution
of non-absorbable
polymer ONLY
Metallic surface
ONLY
Healing and thrombogenicity differences?
NO DRUG PRESENT
Platelet Adhesion and Activation PVDF Durable Polymer vs. Metallic Surfaces
% S
urf
ac
e A
rea
(+
) P
-Se
lec
tin
%
Su
rfa
ce
Are
a (
+)
CD
41
NS p < 0.05
compared to
PVDF
P= NS
p < 0.05
compared to
PVDF
Eppihimer M, Granada JF, TCT2012
Platelet Accumulation on Stent Surface PVDF Durable Polymer vs. Metallic Surfaces
*
*
*
Eppihimer M, Granada JF, TCT2012
Metallic
Surface
Cell
Migration
(mm)
Cell
Morphology
Cell
Size
Cell
Confluence
Cell
Concentration
Surface 1 1.99 ± 0.25 ++ Normal ++ ++
Surface 2 1.62 ± 0.37 ++ Normal ++ ++
Surface 3 1.57 ± 0.33 ++ Normal ++ ++
Surface 4 1.3 ± 0.4 + Elongated - +
Surface 5 1.18 ± 0.43 - Elongated - +
Surface 6 1.08 ± 0.29 + Elongated - -
Endothelial Cell Migration Correlates with Surface Coverage and Morphology
Left figure (modified) courtesy of A. Tellez, SCCR