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Des bioabsorbable stents tct 2010
1. Bioabsorbable Stents
Design Considerations
Robert S. Schwartz, MD
Minneapolis Heart Institute
The Minneapolis The Minneapolis Heart
Heart Institute Institute Foundation
2. Disclosures:
Abbott Vascular: SAB, Research Support
Boston Scientific: SAB, Research Support
REVA: Minor Equity
The Minneapolis The Minneapolis Heart
Heart Institute Institute Foundation
3. Bioresorbable Stents – Generation 1
Leave only natural vessel long term
May reduce long term risk of thrombosis
May reduce need for long term anti-platelet
therapy
Increased options for retreatment (ISR, distal
lesion, CABG)
Increased CT / MR imaging capability
Appeals to concern over permanent implant
Need Improved Deliverability
The Minneapolis The Minneapolis Heart
Heart Institute Institute Foundation
4. Rationale and Goals (from BVS)
Revascularize the vessel like a metallic DES, then
resorb naturally into the body.
Leave no permanent metallic implant.
No permanent scaffold – restores natural vascular
response to physiological stimuli and potentially
permits late lumen expansion.
*Serruys PW, et al., Circulation 1988; 77: 361. Serial study suggesting vessels stabilize 3-4 months following PTCA.
The Minneapolis The Minneapolis Heart
Heart Institute Institute Foundation
5. Desire for a
‘Vascular Restoration Therapy’?
Revascularization Restoration Resorption
Support Full Mass Loss &
Bioresorption
Everolimus Elution
Mass Loss
1 3 6 Mos 2 Yrs
Platelet Deposition Matrix Deposition
Leukocyte Recruitment Re-endothelialization
SMC Proliferation and Migration Vascular Function
Forrester JS, et al., J. Am. Coll. Cardiol. 1991; 17: 758.
Oberhauser JP, et al., EuroIntervention Suppl. 2009; 5: F15-F22.
The Minneapolis The Minneapolis Heart
Heart Institute Institute Foundation
6. Goals from the Rationale
No stimulus for chronic inflammation – potentially
reduces the need for long-term dual antiplatelet
therapy.
Future re-intervention (PCI and CABG) is
facilitated.
Provide compatibility with non-invasive diagnostic
imaging (MR/CT), allowing non-invasive follow-up.
*Serruys PW, et al., Circulation 1988; 77: 361. Serial study suggesting vessels stabilize 3-4 months following PTCA.
The Minneapolis The Minneapolis Heart
Heart Institute Institute Foundation
7. Abbott Vascular Everolimus-Eluting
Bioresorbable Vascular Scaffold
ML VISION Delivery Bioresorbable Bioresorbable
Everolimus
System Device Platform Coating
• Seven • Polylactide (PLLA) • Polylactide (PDLLA) • Similar dose and
generations of • Naturally coating release rate to
MULTI-LINK resorbed, fully XIENCE V
• Fully biodegradable
success metabolized
• World-class
deliverability
All illustrations are artists’ renditions
The Minneapolis The Minneapolis Heart
Heart Institute 7 Institute Foundation
8. Bioresorbable Polymer
Everolimus/PDLLA Matrix
Coating
Thin coating layer
Amorphous (non-crystalline)
1:1 ratio of Everolimus/PLA
matrix
Drug/polymer matrix
Conformal Coating, 2-4 µm thick
Polymer backbone
Controlled drug release
PLLA Backbone
Highly crystalline
Provides device integrity
The Minneapolis
Processed forThe Minneapolis Heart
increased radial
Heart Institute Institute Foundation
9. Porcine Coronary Arteries
4
BVS
Cypher
3
Less Inflammation than
Inflammation Score
2
Cypher
1
Minimal Inflammation
0
1 3 6 9 12 18 24 36 48
Time (months)
Inflammation score ≤ 1 = background
The Minneapolis The Minneapolis Heart
Heart Institute Institute Foundation
10. BVS Stent Objectives
uniform strut distribution
even support of arterial wall
Cohort A
Lower late scaffold area loss
Maintain radial strength
for at least 3-4 months
Storage at room temperature
Improved device retention
Cohort B
The Minneapolis The Minneapolis Heart
Heart Institute Institute Foundation
11. Radial Strength
(mmHg) Radial Strength MSI Testing
1800
1600
1400
1200
1000
991
883
800
600
400
200
0
BVS Cohort B XIENCE V
Radial strength comparable to metal stent at T=0
Tests performed by and data on file at Abbott Vascular.
The Minneapolis The Minneapolis Heart
Heart Institute Institute Foundation
12. What is the Minimum Duration of Radial Scaffolding?
Quantitative angiographic study in 342 consecutive patients at 1, 2, 3, and 4 months
n = 342 patients (n = 93 at 30-day F/U; n = 79 at 60-day F/U; n = 82 at 90-day F/U; n = 88 at 120-day F/U)
p < 0.00001
p < 0.00001
.The lumen appears to stabilize approximately three months after PTCA
Serruys PW, et al., Circulation 1988; 77: 361.
The Minneapolis The Minneapolis Heart
Heart Institute Institute Foundation
13. Radial Strength Over Time
In-Vitro Degradation Testing (soaked at 37° C PBS)
1400
1251
1213 1209 1183
1224
1200 1132 1125 1134
1124 1158
Radial Strength (mmHg)
1000 1127
955
3 – 4 Month Goal
800
600
400
200
0
0 50 100 150 200 250 300
t (days)
Tests performed by and data on file at Abbott Vascular.
The Minneapolis The Minneapolis Heart
Heart Institute Institute Foundation
14. Potential for Mechanical
Conditioning
Design Goals:
Gradual disappearance of Vessel recovers the ability to
supportive scaffold respond to physiologic stimuli
Vascular
Function
Shear stress & pulsatility
Support
Tissue adaptation
Structure and functionality
Mechanical conditioning may lead to improved cellular organization and vascular function
‘Vascular Restoration Therapy’
The Minneapolis The Minneapolis Heart
Heart Institute Institute Foundation
15. Mechanical Conditioning in Pre-
Clinical Model (Porcine)
Transmission Electron Microscopy (TEM) Smooth Muscle α-Actin
Dense
bodies
At 36 months, SMCs are well organized and have undergone
transformation to a functional, contractile phenotype
Tests were performed by and data are on file at Abbott Vascular.
The Minneapolis The Minneapolis Heart
Heart Institute Institute Foundation
16. Bioresorbable Stent Tradeoffs
Degradation profile
Vascular compatibility
vs
Profile
Radial strength
Recoil
Vessel conformability
Standard implant/storage
The Minneapolis The Minneapolis Heart
Heart Institute Institute Foundation
17. REVA Medical – Stent Features
7Fr compatible Coating:
Slide and lock profile Tyrosine-derived
design
Polycarbonate + Ptx
Stent Material:
Tyrosine-derived
Polycarbonate
Iodine impregnated for RO
Loss of radial strength Degradation
Implant 1-year 2-year
The Minneapolis The Minneapolis Heart
Heart Institute Institute Foundation
18. REVA Medical – Polymer
Tyrosine derived polycarbonate polymer specifically formulated for
bioresorbable stent
Benign breakdown products (amino acids, ethanol, and CO2)
Ability to vary degradation rate
Radiopaque (iodine impregnated into polymer)
Same polymer used for drug coating
REVA Clinical Polymer:
86.75% I2DTE-co-10%I2DT-co-3.25%PEG2000carbonate) REVA Tyrosine Derived Polycarbonate Stent
The Minneapolis The Minneapolis Heart
Heart Institute Institute Foundation
19. Metal Alloys – Biotronik
Absorbable Metal Stent (AMS)
5Fr compatible
profile
Conventional No Drug/Drug Coating
stent design
No radiopaque Stent Material:
markers 93% Mg+7% Other
Loss of radial strength Degradation
Implant 6-Wks 3-Months
The Minneapolis The Minneapolis Heart
Heart Institute Institute Foundation
20. Biotronik – Degradation Rate
AMS 2 – Modified Mg Alloy and Design
Slower degradation rate
Improved stent strength
Drug component/delivery?
4-Wk Histology
Images from “Is it a dream? Drug Eluting Absorbable Metal Stent (DREAMS)” presentation at Euro PCR 2007 given by Dr. Ron Waksman
The Minneapolis The Minneapolis Heart
Heart Institute Institute Foundation
22. Bioabsorbable Stents
Design Considerations
Robert S. Schwartz, MD
Minneapolis Heart Institute
The Minneapolis The Minneapolis Heart
Heart Institute Institute Foundation
Editor's Notes
Objective: Position the technology as the next big step in the evolution of stent design.
In order to develop an optimal bioabsorbable DES, and to better our chances for success, we are leveraging technologies we have experience with – technologies that have proven themselves as some of the best technologies in the industry. The delivery catheter we are using is from the Vision stent system. This catheter is recognized as having a high of deliverability. The stent platform has evolved from technology developed by researchers at Duke University over 20 years ago. He stent is made from poly lactic acid, or PLA, a material that is absorbed by natural processes in the body. The coating is also made from PLA. The polymer is mixed with everolimus to form a matrix. The drug we are using on the BVS stent is everolimus – the same drug used in our Xience V stent. Although the drug is eluted from a bioabsorbable coating, the release rate is similar to that of Xience V.
Here you see images of the stent that was used in the first 30 patients in the ABSORB trial (BVS A), compared to the new stent design that will be tested in the next cohort of patients (BVS B). Some of the improvements are obvious from these photos. The new design has a more uniform strut distribution, which should lend itself to a more even support of the vessel wall. The regions of unsupported surface area within the cells are also considerably smaller. We have also made some processing enhancements that have contributed to yielding a stent that demonstrates less late stent area loss and higher radial strength, in bench and pre-clinical testing.
Objective: Identify the key bioresorbable stent technology attributes.
Highlight key features of FIM Design REVA’s FIM or 1 st generation stent design includes: - Innovative polymer specifically designed with Rutgers University for stent application - Unique stent design that allows for standard balloon deployment and low recoil however, makes the stent rather bulky. - Polymer is impregnated with Iodine making the entire stent radiopaque - The stent is estimated to lose radial strength in about 6 months and completely degrade in 2 years
Highlight polymer material features - Drug coating and stent backbone is made from the same polymer - By-products from degradation are safe - Degradation rate is tuneable
Highlight Biotronik’s AMS features - The metal alloy consists of 93% Mg and 7% rare elements - the conventional stent design allows for standard balloon deployment - there are no radiopaque markers on the stent only on the balloon - the AMS stent degrades much quicker than the polymer technologies. The AMS loses its radial strength in a couple of weeks and completely degrades in 3 months
