Transcript Radial strength

CORONARY STENTS
yStent
DR KRISHNA KUMAR. K
MD DM FACC
1977
Balloon Angioplasty ( March 1977)
Bare Metal Stent (1986)
Brachytherapy
Cutting Balloon
Directional Atherectomy
Extraction Atherectomy
Laser Atherectomy
Perfusion Balloon
Rotational Atherectomy
Angioscopy
Doppler Flow
Intravascular Ultrasound
Optical Coherence Tomography
Palpography
Pressure Measurements
Thermography
Virtual Histology
Drug Eluting Stent (2002)
1st Gen
Drug Eluting Stent (2005
2nd gen
2011
Historical Overview
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1967 1977 1978 1987 -
Coronary Artery Bypass Graft Surgery (CABG)
Percutaneous Transluminal Coronary Angioplasty (PTCA)
Idea of stent conceived
First balloon expandable stent (Palmaz-Schatz™) implant in
human coronary artery
1992 - Julio Palmaz and Richard Schatz: If you could only
coat this stent with a drug…..
1993 - Introduction of Coronary Stents (BiodivYsio PC polymer
coated stent)
2002 - Cypher Drug-eluting Stent
2003 - Taxus Drug-eluting Stent
2005 - Endeavor Drug-eluting Stent
2006 - Xience V Drug-eluting Stent
2007 - Endeavor Sprint,
2008- Endeavor Resolute and Promus Drug-eluting Stents
2009- Biodegradable polymer stents
2010- Bioabsorbable stents
Future – Integrity- Newer generations of Bare-metal Stents and Drug-eluting Stents
1977
• Gruntzig – Plain balloon angioplasty.
• Dissection and acute vessel closure
• Recoil
• Restenosis
• In 1986, working in Toulouse, France,
Jacques Puel and Ulrich Sigwart
implanted the first stent into a human
coronary artery
In 1986, working in Toulouse, France,
Jacques Puel and Ulrich Sigwart
implanted the first stent into a
human coronary artery
TLR – 28%
TVR – 38%
2% ST
BVS Needs a drug to prevent restenosis
The Four Key Components of STENT Design
Scientific Design & Integration
Stent
Platform
Type
of Drug
Stent Delivery
System
Type of
Polymer
Approach to Stent Material-ALLOY
• A new stent material had to meet all of the
following requirements:
Cobalt Chromium Compared to
Stainless Steel
• L-605 cobalt chromium and 316L stainless steel have a protective
chromium oxide layer and similar biocompatibility.
• Because of the different element mix, cobalt chromium is stronger
and more radiopaque than stainless steel.
Cobalt Chromium Strength
• Cobalt chromium is 76% stronger than stainless
steel.
• Strength of cobalt chromium allows cc stent to
have thin struts while maintaining better radial
strength.
New alloy
• Properties of Platinum Chromium:
• Over 2 times more dense than Iron or
Cobalt, providing superior radiopacity
• Increases strength when alloyed with 316L
Stainless Steel
• Vascular compatibility
• Platinum Chromium takes strength,
flexibility & radiopacity a generation
beyond Cobalt Chromium.
Advantages
• Radial strength,
• Exceptional deliverability
• Hgh visibility.
• The thin-strut stent is designed for improved conformability, minimal
recoil and uniform lesion coverage and drug distribution.
• The advanced low-profile delivery system, coupled with the
radiopacity, facilitates precise delivery of the stent across
challenging lesions.
Terms
Connecting
Link
Crests
Ring
Element Length
Crests per Ring
6
5
5
1
1
4
2
3
6 Crests per
Ring
4
3
2
5 Crests per
Ring
Crests per Ring
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1
2
3
4
Less Crests
Less Scaffolding
Easier to reduce profiles
Less Expansion Range
More Crests
More Scaffolding
1
2
3
4
5
6
Connections per Ring
• Less
• More Flexible
• Less Scaffolding
More
Less Flexible
More Scaffolding
Element Length
• Shorter
• Better scaffolding
• Higher radial strength
• Wider
• Poorer scaffolding
• Lower radial strength
Stent Struts
Width
• Strut Thickness
– Distance from the
inner stent surface to
the outer stent surface
Thickness
Thin Strut Advantage
Reduce deep wall trauma
35%
6-month binary restenosis
31%
30%
26%
25%
20%
15%
10%
5%
0%
15%
Thin Thick
Multi-link®
18%
Thin Thick
Multi-link®
ISAR STEREO 1 ISAR STEREO 2
Strut thickness appears to
have a significant impact on
long-term restenosis after
stent implantation.1,2
Strut Thickness Tradeoff
Thinner
Thicker
Less Visible
Less Metal in the Vessel
More Visible
More Metal in the Vessel
Radial strength
is generally defined as the pressure which a stent exerts
to the vessel or lumen into which it is implanted.
Longitudinal Foreshortening
Peak to peak
Peak to Valley connector
Four Stent Design Families
MULTI-LINK
VISION platform
MULTI-LINK 8
platform
Firebird2
platform
Express2
platform
Peak-tovalley
Offset peak-to-peak
Element platform
ProNova
platform
Cypher Select
platform
Coroflex Blue
platform
Promus Premier
platform
PRO-Kinetic
Energy
platform
Mid-strut
connector
Synergy
platform
Driver
platform
Integrity
platform
Juno
platform
Nobori
platform
Veriflex
platform
Peak-topeak
Images on file at Abbott Vascular.
Information contained herein is not intended for physicians
from France or the United States.
Bench Testing: Longitudinal Stent
Compression
Amount of longitudinal compression under 50 gf
Effect of Stent Design
14
Longitudinal stent compression (mm)
12
Weaker
10
8
13.2
6
4
4.6
2
1.3
1.4
1.6
XIENCE
PRIME
81 mmin
0.0032
CoCr
XIENCE V
0.0032
81 mmin
CoCr
TAXUS
Express
132 mm
0.0052
in
SS
2.6
2.5
Firebird2
0.0034
86 mmin
CoCr
Endeavor
(Driver)
91 mmin
0.0036
CoNi
2.9
5.3
3.2
1.8
2.7
2.8
3.6
Stronger
0
Peak-to-valley designs
Nobori
0.0054
137 mm
in
SS
Integrity BioMatrix
Resolute
Flex
91 mmin
137 mmin
0.0036
0.0054
CoNi
SS
Peak-to-peak designs
Tests performed by and data on file at Abbott Vascular.
Information contained herein is not intended for physicians
from France or the United States.
TAXUS
Liberte
97 mmin
0.0038
SS
Cypher
Select+
140 mmin
0.0055
SS
PROCoroflex
Kinetic
Blue
66 mmin
Energy
0.0026
0.0024
CoCr
61 mmin
CoCr
ProNOVA
0.0024
61 mmin
CoCr
Mid-strut connector designs
Element
0.0032
81 mmin
PtCr
Offset peak-topeak design
What can result from LSD?
The Spectrum of Adverse Events
Procedural Events
Post-Procedural Events
Reported Clinical Events from Longitudinal Stent Deformation1,2,3,4:
Poor lesion coverage
Stent thrombosis
Plaque prolapse
Restenosis
Post-dilatation of deformed
stent
Increased vessel injury
Difficulty re-entering stent
for post dilatation
Dissection
Lack of tissue or lesion coverage
Death
Additional stenting
Prolonged procedure as a
result of additional
intervention
Cardiac surgery
Leibundgut, PCR 2012
OCT image showing stent crowding as a result of LSD5
1. Mamas, M. EuroIntervention, March 2012. 2. Williams, P. EuroIntervention, Oct. 2011. 3. Source: Bartorelli et al., Stent longitudinal distortion: strut separation (pseudo-fracture) and strut
compression (“concertina” effect), EuroIntervention June 2012. 4.Stone, G. Everolimus-Eluting Stents 2011/2012 Stent Design Evolution and Clinical Trial Update, TCT 2011. 5.
Leibundgut, G et al. Longitudinal Compression of the Platinum-Chromium Everolimus Eluting Stent During Coronary Implantation. Catheterization and Cardiovascular Interventions.
Accepted Article. Doi 10.1002/ccd.24472.
Information contained herein is not intended for physicians
from France or the United States.
Stent Platform Characteristics
• Struts thickness
– Thinner struts result in:
• Lower profile stent
• Improved flexibility of the stent
• Strut geometry
– For DES, the greater the surface area, the higher the quantity of drug that can be
bound and delivered to target tissue.
• Material / composition
– Common stent materials include stainless steel, cobalt alloy,
nitinol, tantalum.
• Cell area
• Cell design (Open versus Closed Cell)
– Open cell design offers less coverage but more flexibility, side branch access and
conformity to the vessel wall.
– Closed cell design offers more coverage for large plaque burden but less flexibility.
Stent Design Summary
Improve Scaffolding:
More crests per ring
• Shorter element length
• More connections per
ring
Improve Flexibility:
• Shorter element length
• Less connections per
ring
• Shaped or staggered
connections
Visibility:
• Thicker struts
Profiles:
• Thinner struts
• Less crests per ring
• Expansion Range:
• More crests per ring
Metal in Vessel:
• Thicker struts
• More crests
• Shorter element length
Stent Delivery System
• Balloon-expandable
– Factory mounted on a
balloon delivery system
• Self-expanding
– Stent placed under a sheath
– Sheath retraction allows
stent expansion
Additional Stent Design
Considerations
Balloon material - determines control of stent expansion and
trackability.
Balloon Markers (visibility/location) - provide for ease and accuracy
of stent placement.
Discrete Balloon length - minimum balloon overhang post
deployment and aid in reducing potential risk of edge dissection.
Stent Security – describes the ability of the stent to stay on the
delivery system, especially in tortuous trackability or during system
withdrawal.
An Ideal Stent Delivery System
Minimal Balloon Overhang
Stent Platform - Xience V and Promus DES
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Stent platform - Multi-link Vision
Slotted tube design
Cobalt Chromium – increases strength and visibility
Open-cell design enhance vessel conformability
Information available on company website and subject to change
Stent Platform – Endeavor/Sprint, Endeavor Resolute DES
Earlier Generation Medtronic Stents
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Stent platform – Driver
Modular design - thin, edgeless struts enable atraumatic delivery
Cobalt alloy composition increases strength and visibility
Open-cell design and short modular elements enhance vessel
conformability
The Preferred Mechanism of
Action (MOA)
The drug would ideally act early in the G1
phase,
preventing entry into the S phase
G0: Resting (zero) state
G1
M
G0
G1: Cell clears “checkpoints” in
readiness to grow and prepare
chromosomes for replication
Cell
cycle
S:
DNA duplicates
G2: Cell duplicates organelles,
prepares for M
G2
S
M:
Cell physically divides
2 Drugs with 2 Different Targets:
Pimecrolimus-Paclitaxel
Isoflavone-Sirolimus
Dexamethazone-Zotarolimus
Sirolimus, Biolimus A9
Everolimus, Zotarolimus
Tacrolimus
Pimecrolimus
Paclitaxel
Isoflavone
Inhibitor
Smooth Muscle Cell Mechanism of
Action (MOA)
Some drugs are cytostatic and stop proliferation
before the cell is committed to division
Ideal Drug for DES
 Proven Clinical Performance
– Efficacious
– Safe in systemic uses
 Preferred Mechanism of Action (MOA)
– Cytostatic
– Non-inflammatory
 Wide Therapeutic Window
– Excellent tissue compatibility
– Effective at multiple doses with minimal toxicity
 Drug Stability
– Product yield (manufacturing)
– Shelf-life
All illustrations are artist renderings.
Polymers
• Durable (permanent polymer)
• Bio-degradabale polymer
Polymer Coating Configurations
Matrix Only
Design
Stent
Primer and
Matrix Design
Stent
Primer, Matrix,
and Topcoat
Design
Stent
Primer: May be applied
to improve adhesion
to stent
Matrix Coating:
Mixture of drug and
polymer
Topcoat: May be
applied if needed to
slow the release rate
of the drug
High Drug Loading Capacity
A polymer with a high drug loading capacity,
allows for a thin polymer coating
7.8 µm
Polymer Thickness
on outer diameter (O.D.)
7.8 µm
System Crossing
Profile
.041"
Directional Drug Delivery
(abluminal preference)
• Selective coating on the
outside surface of the stent
– Reduced drug/polymer
– Luminal surface BMS
– Drug only where needed
Properties of an Ideal DES Polymer
 Hemocompatibility
– Non-thrombogenic and non-inflammatory
– Proven in other blood contacting applications
 Controlled release of the drug
– Release throughout the restenosis cascade
– Complete release of drug over time
 High drug loading capacity
– Thin coating thickness
– Minimizes crossing profile
 Uniform Coating Integrity
– Toughness for coating integrity during delivery
– Elastic for coating integrity upon expansion
Adhere to the stent, but not the balloon
Can we do away with the
polymer?
Polymer free drug-delivery
Do we need a scaffold permanently?
Late Disease Progression
Accelerated by the Presence
of a Stent?
Disease Progression: PTCA
versus BMS
1Guiteras-Val,
P., et al. Am J Cardiol. 1999;83:868-874. / 2Hatrick, R., et al. EuroIntervention. 2009;5:121-126. / 3Kimura, T., et al. Circulation. 2002;105:2986-2991.
The Clinical Need for a Bioresorbable Vascular
Scaffold
Rationale
Vessel scaffolding is only needed transiently*
Rationale
Vision
Vision
Potential
Benefits
Potential
Benefits
Improve Long Term Outcomes for Patients
by Leaving No Scaffold Behind1
 Restore the vessel to a more natural state, capable of
vascular function
natural
 Eliminate chronic sources of vessel irritation and inflammation
 Vessels remain free for future treatment options (i.e. CABG)
 Reduce the need for long-term DAPT2
 Allows for use of non-invasive imaging techniques (CCTA)
 Improve patient quality of life
*Serruys PW, et al., Circulation 1988; 77: 361. Serial study suggesting vessels stabilize 3-4 months following PTCA.
1 – Small platinum markers at scaffold edges remain for fluoroscopic landmarking. 2. The Absorb IFU recommends DAPT for a minimum of 6 months.
Resorb: Absorb is Resorbed by a Natural
Process
Scaffold Strut
Lactic Acid
DIFFUSION
Lactic acid is readily converted to lactate,
a common fuel source for multiple
metabolic pathways1
Lactic Acid
Lactate
Lactate
Intracellular
Mitochondrion
H2 O
CO2
Krebs
Cycle
BioMime Morph
Unmet Clinical Need
TM
- Sirolimus Eluting Coronary
Stent System
 A stent that matches the diameter differentials from distal to
proximal in long diffused lesions. One & done.
 = D1
Device Description
 Unique tapered coronary stent.
 Tapering diameters (1/2 sized)
 = D2
 Distal to Proximal – 3.50→3.00 mm & 3.00→2.50 mm
 Longest lengths – 50, 60 mm
 Mounted on a newly created extra support Rx balloon catheter
with tapered diameters
D1 > D2
 1.25 µg/mm2 of Sirolimus, 30-days release kinetics.
 Biodegradable polymer base
Ø 3.50
Ø 3.00
Ø 3.00
Ø 2.50
Proximal
l – 50, 60 mm
Distal
Ø 3.50
Ø 3.00
Ø 3.00
Ø 2.50
Actual device photographs. Data on file Meril Life Sciences.
NEW DESIGNS
• M –GUARD
• STENTYS
• DEDICATED BIFURCATION STENTS
• Endothelial progenitor cell capturing stent
Pro-Healing approach
• Endothelial progenitor cells have been
identified as a key factor in the reendothelialization process after stent
implantation.
• Orbus
• HEALING – II Study
Surfaces to Encourage Cell Growth
Bioactive surfaces to accelerate functional endothelialization
Orbus – EPC Capture
Nanotextured Surfaces
cell
protein
drug
peptide
Peptide
linkers
device surface
Example of IrOx
Cell specific peptide linkers (Affinergy)
What will be the future?
DES
Thin strut Bio-absorbable radio-opaque scaffold.
Potent limus group of drug / multiple drugs.
Non-polymer drug delivery, nano particle based.
Focus will be on Prohealing and fast re-endothelialization
Dedicated stents for bifurcations and small vessels
Definitely we can expect more….
Thank You