1. The Promise of ABSORB Bioabsorbable Vascular Scaffolds
Gregg W. Stone MD
Columbia University Medical Center
The Cardiovascular Research Foundation

2. Consulting: Boston Scientific, Reva
Gregg W. Stone, MD
Consulting:
Boston Scientific, Reva

3. Stone GW et al. JACC 2011 (abstract)
SPIRIT III: Target Lesion years
TAXUS Express (n=332)
XIENCE V (n=669)
30%
5-year HR
0.64 [0.46, 0.89]
25%
p=0.008
1-year HR
20%
19.0%
0.56 [0.34, 0.90]
p=0.01
TLF (%)
Δ6.3%
15%
9.2%
12.7%
10%
Δ3.8%
~1.8%/yr event rate after year 1 5%
5.4% 0% 6 12 18 24 30 36 42 48 54 60
Months
Number at risk
XIENCE V
669
646
616
601
582
571
565
548
537
529
521
TAXUS
332
310
288
274
269
262
255
248
243
231
223
TLF = cardiac death, target vessel MI, or ischemic-driven TLR
Stone GW et al. JACC 2011 (abstract)

4. Target lesion failure (%) Stone GW et al. JACC 2011 (abstract)
SPIRIT IV: Target Lesion years 25
XIENCE V (n=2458)
TAXUS Express (n=1229) 20
HR [95%CI] = [0.63, 0.97]
p=0.004
HR [95%CI] =
0.71 [0.56, 0.90]
p=0.001
HR [95%CI] =
0.61 [0.46, 0.81]
p=0.02 15
11.7%
Target lesion failure (%)
Δ 2.5% 10
6.7%
9.2%
Δ 2.7% 5
~2.6%/yr event rate after year 1
4.0% 3 6 9 12 15 18 21 24 27 30 33 36
Months
Number at risk
XIENCE V
2458
2390
2364
2323
2281
2238
2212
2187
2162
2132
2116
2095
2074
TAXUS
1229
1166
1138
1119
1095
1069
1060
1049
1029
1019
1008
994
979
TLF = cardiac death, target vessel MI, or ischemic-driven TLR
Stone GW et al. JACC 2011 (abstract)

5. Etiology of DES events beyond 1 year
Very late thrombosis and restenosis
Possible causes
Uncovered stent struts (thrombosis)
Persistent stimulation of SMCs, from adherent fibrin and/or loss of normal vessel curvature
Abnormal shear stress from protruding struts and/or loss of cyclic strain relief (compliance mismatch)
Chronic inflammation due to late foreign body reactions and polymer hypersensitivity
Positive remodeling with strut malapposition
Strut fracture
Neoatherosclerosis

6. Metallic Stent – A caged lumen doomed to get reduced, or a cage doomed to get malapposed
Compensatory Expansive Remodeling of EEM BL 1Y
PIT 5Y + IT FA
Metallic stent is the cage
Late acquired malapposition
Struts
Lumen Reduction -
Lumen Reduction
Metallic Struts
Lumen Reduction by Intrastent Growth of tissue -
c/o Patrick Serruys -

7. Possible Advantages of BVS
Restoration of normal vasomotion, with NO production
Restoration of normal shear stress and cyclic strain
Restoration of normal vessel curvature
Reduced risk of very late polymer reactions
Avoidance/resolution of positive remodeling and stent malapposition
Avoidance/resolution of late strut fractures
Less neoatherosclerosis
Un-jailing of side-branches
Plaque regression
MRI/CT imaging follow-up
The emotional appeal of normal vessel architecture

8. Bioresorbable Scaffold – A new treatment Paradigm for Atherosclerotic Plaque
Compensatory Expansive Remodeling of EEM 2Y 6M BL
PIT + IT FA
Lumen Enlargement by Plaque Regression
Struts -
Lumen Reduction
Scaffolding
Lumen Enlargement By Bioresorbable Scaffolding -
c/o Patrick Serruys -

9. Late Loss with Xience V vs. Absorb BVS
Cumulative frequency distribution (mm)
6 month (SPIRIT II): 0.17 ± 0.32 mm (N=97)
24 month (SPIRIT II): 0.33 ± 0.37 mm (N=97)
Late loss (mm)
Claessen BE et al. Circ CV Int. 2009;2:339-47

10. Late Loss with Xience V vs. Absorb BVS
Cumulative frequency distribution (mm)
6 month (SPIRIT II): 0.17 ± 0.32 mm (N=97)
24 month (SPIRIT II): 0.33 ± 0.37 mm (N=97)
6 month (Cohort B): 0.19 ± 0.18 mm (N=42)
24 month (Cohort B): 0.27 ± 0.20 mm (N=38)
Late loss (mm)
Claessen BE et al. Circ CV Int. 2009;2:339-47
Serruys PW. ESC 2012

11. BVS: Evidence of substantial lumen enlargement due to plaque regression (cohort A pt)
Pre-PCI
Post-PCI
6 months
2 years
5 years
deze biodegradeerbare stent kan stabiliseren een inflammatoire plaque. Op de animatie zien we een plaque groeien met het optreden van een dunne cap – met tenslotte het scheuren van de cap met een stolsel. Een biodegredeerbare stent zou dit kunnen voorkomen. Op de Virtuele histologie van de plaque, zien we de necrotic core, de kern van het vernietigd weefsel van de plaque in contact iis met het lumen van het bloedvat.
Post-stenting zien we de appositie van de stent. Na zes maanden zijn de stent struts nog zichtbaar. Na 2 jaar is er een laag van fibrotisch weefsel dat de nectrotic core afdekt.
Vessel area (mm2)
15.72
15.34
14.09
13.76
Mean lumen area (mm2)
6.95
6.17
6.56
8.09
Plaque area (mm2)
8.78
9.17
7.54
7.07 11

12. Long term anatomical and functional assessment of the scaffold by MSCT
c/o Patrick Serruys

13. CFD curves of vessel area, plaque area and lumen area on MSCT at 18 and 60 months%
Mean Vessel area at 18 months
Mean Vessel area at 60 months
Mean Plaque area at 18 months
Mean Plaque area at 60 months
Mean Lumen area at 18 months
Mean Lumen area at 60 months
mm2
c/o Patrick Serruys

14. Sealing and shielding of plaques after scaffold implantationBL BL 6M
24M
Example of capping a calcified plaque
Brugaletta S et al. Atherosclerosis 2012

15. Igaki-Tamai Stent (2000)
Hideo Tamai, MD
Died 14 Feb, 2009

16. I-T stent @10 Years! C D E A B C E D B A Onuma Y et al. EuroInt 200916

17. ABSORB III + IV
A clinical program consisting of integrated randomized trials designed to:
Achieve approval of ABSORB in the US
and
Demonstrate superiority of ABSORB compared to best in class DES

18. ABSORB III + IV Clinical Trial Program
2,250 pts with up to 2 de novo lesions in different epicardial vessels enrolled, with follow-up for at least 5 years, at up to 122 US and non-US sites
2,000 pts randomized 2:1 ABSORB v XIENCE (+50 lead-in pts and 200 pt non-randomized angio/IVUS/OCT/VM FU cohort)
RVD: mm; Lesion length: ≤24 mm
Scaffold diameters: 2.5, 3.0 and 3.5 mm Scaffold lengths: 12, 18, and 28 mm
Primary endpoint (n=2,000): TLF at 1 year (powered for noninferiority) – US approval
Key question – will it support pricing and reimbursement in our markets of interest?
PIs: SG Ellis, DJ Kereiakes
Study chairman: GW Stone

19. ABSORB III + IV Clinical Trial Program Co-PIs: SG Ellis, DJ Kereiakes
ABSORB IV
2, ,000 additional pts rand 1:1 ABSORB v XIENCE
Up to 6,000 total pts with up to 2 de novo lesions in different epicardial vessels randomized, with follow-up for at least 5 years, at up to 160 US and non-US sites
RVD: mm; Lesion length: ≤24 mm
Scaffold diameters: 2.5, 3.0 and 3.5 mm Scaffold lengths: 12, 18, and 28 mm
Primary endpoint (n = 4,500 – 6,000): TLF between 1 and 5 years (landmark analysis, powered for superiority)
Key question – will it support pricing and reimbursement in our markets of interest?
PI: GW Stone
Co-PIs: SG Ellis, DJ Kereiakes