1. Bioabsorbable Stent: Unsolved Issues and Challenges
Mitchell W. Krucoff MD, FACC
Professor of Medicine / Cardiology
Duke University Medical Center
Director, Cardiovascular Devices Unit
Duke Clinical Research Institute

2. 2006: Questions About DES Safety

3. 49 RCTs, 50,844 patients, ARC ST
Palmerini T et al, Published online March 23, 2012 DOI: /S (12)

4. 1 Year Definite and Definite/Probable ARC ST: 2nd Gen DES safer than BMS
Palmerini T et al, Published online March 23, 2012 DOI: /S (12)

5. 2014: DAPT Study: Persistent Questions About New DES Safety
Mauri L et al, NEJM 2014

6. JAMA: DAPT BMS Total cohort: no interaction with DES, BMS

7. Bioresorbable Polymer
Everolimus/PDLLA Matrix Coating
Thin coating layer
Amorphous (non-crystalline)
1:1 ratio of Everolimus/PLA matrix
Conformal Coating, 2-4 m thick
Controlled drug release
PLLA Scaffold
Highly crystalline
Provides device integrity
Processed for increased radial strength
Drug/polymer matrix
Polymer backbone
Agrawal, et al., Biomaterials 1992

8. ABSORB Cohort A Intravascular Imaging at 5 years
Late lumen gain on OCT
IVUS
OCT
ABSORB
Cohort A
MLA
6.35 mm2
6 month follow up
In fact, 5-year follow up of Cohort A patients is showing that late lumen gains at 2 years are preserved at 5 years. And the characteristic appearance of a so-called golden tube on OCT is indicative of the beneficial remodeling that can take place after scaffold resorption.
Neo-media um
MLA
8.77 mm2
5 year follow up
Caution: Investigational device.
Limited by Federal U.S. law to
investigational use only.
R.J. van Geuns, PCR Images courtesy of Thoraxcenter, Erasmus MC, Rotterdam, The Netherlands

9. ABSORB Cohort A Vasomotor Function Testing at 2 Years
The reappearance of vasomotion in the proximal, distal, as well as treated segments in response to methergin or acetylcholine suggests that vessel vasoreactivity has been restored and that a physiological response to vasoactive stimulus might occur anew.
Serruys, PW, et al. Lancet 2009; 373:

10. ABSORB: Comprehensive AV-Sponsored Clinical Trial Program
2011
2012
2013
2014
2015
2016
ABSORB Cohort A n = 30; FIM
5 Y
ABSORB Cohort B n = 101; FIM
1 Y
2 Y
3 Y
4 Y
5 Y
ABSORB EXTEND n = ~800, Registry
2 Y
3 Y
1 Y
Enrollment & Follow-Up
ABSORB II n = ~501, International RCT
2 Y
3 Y
1 Y
Enrollment & Follow-Up
ABSORB FIRST n = ~1,800, International Registry
1 Y
Enrollment & Follow-Up
ABSORB III n = ~2,200, US Pivotal RCT
Enrollment & Follow-Up
1 Y
2 Y
ABSORB Japan n = ~400, Japan Pivotal RCT
Enrollment & Follow-Up
2 Y
1 Y
ABSORB China n = ~440, China Pivotal RCT
Enrollment & Follow-Up
2 Y
1 Y
ABSORB IV* n = ~3,000, US RCT
UK Registry n = 1000, UK Registry
Enrollment & Follow-Up
1 Y
Total Pts Studied
n=~599
n~965
n~5,709
n~7,609
n~8,709
n~9,709
Each trial n reflects total patients Data effective September 2013
*ABSORB IV trial is in the planning stage and subject to change.
Caution: Investigational device. Limited by Federal U.S. law to
investigational use only. 10

11. Company Confidential © 2013 Abbott
ABSORB Cohort A (Intent-To-Treat Population, ITT) Excellent Long-Term Safety Data Out to 5 Years
RESTORATION
RESORPTION
6 Months 30 Patients
1 year 29 Patients**
2 Year 29 Patients**
5 Year
29 Patients**
Ischemia Driven MACE***
1 (3.3%)*
1 (3.4%)*
Cardiac Death
0 (0.0%) MI
Q-Wave MI
Non Q-Wave MI
Ischemia Driven TLR
by PCI
0 (0.%)
by CABG
Scaffold Thrombosis Def/Prob
* Same patient – this patient also underwent a TLR, not qualified as ID-TLR (DS = 42%)
** One patient withdrew consent and missed the 9, 12, 18 month and 2, 3, and 4 year visits; two patients died from a non-cardiac causes, one at 706 days and one at 888 days post procedure
*** MACE – Composite endpoint comprised of cardiac death, myocardial infarction (MI) and ischemia-driven target lesion revascularization (TLR) by PCI or CABG
Serruys, TCT, 2011
Company Confidential © 2013 Abbott 11

12. ABSORB Cohort B (ITT) Excellent Long-Term Safety and Efficacy Data Out to 3 Years
Cardiac Death (%)
Myocardial Infarction n (%)
Q-wave MI
Non Q-wave MI
Ischemia Driven TLR n (%)
PCI
CABG
MACE n (%)
30 Days
6 Months
n = 101
2 (2.0)
3 (3.0)
5 (5.0)
1 year
7 (6.9)
4 (4.0)
2 years
n = 100*
9 (9.0)
TVF n (%)
11 (11.0)
6 (6.0)
TLF n (%)
3 years
10 (10.0)
7 (7.0)
13 (13.0)
Scaffold Thrombosis Def/Prob n (%)
0 (0.0)
*One patient lost to follow-up
MACE: cardiac death, MI, ischemia-driven TLR
TVF: cardiac death, MI, ischemia-driven TLR, ischemia-driven TVR
TLF: cardiac death, MI at TV, ischemia-driven TLR
Dudek, D., ACC 2012.

13. ABSORB Cohort B – Group 1 (ITT) Excellent Long-Term Safety and Efficacy Data Out to 4* Years
Non-Hierarchical
6 Months
12 Months
2 Years
3 Years
4 Years
N = 45
N = 44*
Cardiac Death %
Myocardial Infarction % (n)
2.2 (1)
2.3 (1)
Q-wave MI
Non Q-wave MI
Ischemia driven TLR % (n)
4.4 (2)
4.5 (2)
CABG
PCI
Hierarchical MACE % (n)
6.7 (3)
6.8 (3)
Hierarchical TVF % (n)
9.1 (4)**
No new MACE between 1 year and 4 years
No scaffold thrombosis by ARC or Protocol
*One patient lost to FUP
**Non-TLR TVR at 957 days

14. Study Flow and Follow-up
Randomized 2:1
N=2008 (ITT)
ABSORBTM N=1322
XIENCE
N=686
N=4 lost to follow-up
N=6 withdrew consent
N=6 lost to follow-up
N=3 withdrew consent
ABSORBTM
N=1312
XIENCE
N=677
12-month Follow-up
99.2% Complete
98.7% Complete

15. Months Post Index Procedure
Target Lesion Failure
100%
AbsorbTM BVS (n=1322)
XIENCE CoCr-EES (n=686)
Diff [95% CI] =
1.7% [-0.5% to 3.9%]
Psuperiority=0.16
20%
15%
10% 5% 0% 1 2 3 4 5 6 7 8 9 10 11 13
7.7%
6.0% 12
80%
60%
TLF (%)
40%
20% 0% 1 2 3 4 5 6 7 8 9 10 11 12 13
Months Post Index Procedure
No. at Risk:
AbsorbTM
1322
1254
1230
1218
1196
XIENCE
686
661
651
643
634

16. 1-Year TLF: Subgroup analysis
AbsorbTM
(N=1322)
XIENCE
(N=686) RR
(95% CI)
Relative Risk
p-value (interaction)
Age ≥64 years
8.1%
5.9%
1.37 ( )
0.69
Age <64 years
7.4%
6.2%
1.19 ( )
Female
8.5%
1.16 ( )
0.68
Male
5.5%
1.36 ( )
Diabetes
10.7%
9.1%
1.18 ( )
No diabetes
6.3%
4.6%
1.38 ( )
Unstable angina/recent MI
6.5%
6.6%
0.98 ( )
0.35
Stable CAD
8.3%
5.8%
1.42 ( )
Single TL/TV treated
7.7%
1.32 ( )
0.50
Dual TL/TV treated
9.4%
11.5%
0.81 ( )
Clopidogrel
8.0%
6.8%
1.17 ( )
0.43
Prasugrel or ticagrelor
7.1%
4.3%
1.63 ( )
ACC/AHA class A or B1
2.2%
3.05 ( )
0.07
ACC/AHA class B2 or C
8.2%
7.5%
1.10 ( )
Lesion length <11.75 mm
7.9%
4.8%
1.64 ( )
0.23
Lesion length ≥11.75 mm
7.3%
1.06 ( )
RVD <2.63 mm
9.8%
7.8%
1.27 ( )
0.90
RVD ≥2.63 mm
5.7%
1.34 ( )
Favors AbsorbTM
1.0
Favors XIENCE

17. Device Thrombosis to 1 Year
AbsorbTM
(N=1322)
XIENCE
(N=686)
p-value
Device Thrombosis (def*/prob)
1.54%
0.74%
0.13
- Early (0 to 30 days)
1.06%
0.73%
0.46
- Late (> 30 to 1 year)
0.46%
0.00%
0.10
- Definite* (1 year)
1.38%
0.21
- Probable (1 year )
0.15%
0.55
*One “definite ST” in the AbsorbTM arm by ITT
was in a pt that was treated with XIENCE

18. Median based on pooled AbsorbTM and XIENCE
Outcomes by QCA RVD 2.25 mm
RVD <2.25 mm
(median 2.09 mm)
RVD ≥2.25 mm
(median 2.74 mm)
TLF: Pint diff = 0.31
ST: Pint diff = 0.12 TM
1-Year Events (%)
# Events: 31 11 2 71 30 9 3
# Risk:
241
133
238
1067
542
1058
540
Median based on pooled AbsorbTM and XIENCE

19. 1-Year ST in Very Small Vessels
Impact of Post-Dilatation and Pressure
RVD <2.25 mm TM
Stent thrombosis (%)
AbsorbTM:
11 / 238
6/74
5 / 164
2 / 105
XIENCE:
2 / 133
2/79
0 / 54
0 / 36

20. 1,800 complex Xience vs. Absorb Propensity Matched Comparison
Tamburino C et al, JACC Intervention 2016 in press

21. Do We Know What We Know About Bioresorbable Scaffold?
Breakthrough technology: NOT a permanent implant
Comparator: 1st Gen scaffold vs. State of art metal DES
We have a lot to learn about scaffold:
Implantation technique
Design strengths/limitations

22. Progression Towards Thinner Struts
Gen 1 DES
Gen 1 DES
Gen 2 DES
Gen 2 DES
Strut Thickness:
140 µm
Coating Thickness: 12.6 µm
Strut Thickness:
132 µm
Coating Thickness: 19.6 µm
Strut Thickness:
91 µm
Coating Thickness: 4.8 µm
Strut Thickness:
81 µm
Coating Thickness: 7.8 µm
…it is in this context that we believe that the progression towards thinner stent struts is important.
Shown are the left are the actual SEM cross sections for the first generation of drug eluting stents, for which the strut thickness greatly exceeds 100um. On the right is the Xience V stent with a strut thickness of 81 um.
Also of note is the thin outline of the actual polymer coating around the stent strut for Xience V. The coating thickness is about 8um for Xience V compared to 13-20um for the first generation of DES on the left. This difference is quite visible in the micrographs.
Abluminal coating thickness represented

23. Bioabsorbable stent: What Do We Still Need to Know
Vs Best In Class DES: Device dimensionality
What is design related
What is operator technique related
More complex lesion outcomes?
Clinical long term benefits?
Benefit/risk of long DAPT?
Japan vs. USA—alike or different?

24. Absorbable Stent: What Do We Still Need to Know? Conclusions
Bioabsorbable stents designed to address unmet needs:
Very late stent thrombosis
Vascular restoration at stented sites
Long DAPT
Accruing data, we still need to know:
Proof of long term benefits
Behaviour in complex anatomy
Dimensionality of device benefit/risk:
Operator technique
Regional/national variability

25. Bioabsorbable Stent: Unsolved Issues and Challenges
Mitchell W. Krucoff MD, FACC
Professor of Medicine / Cardiology
Duke University Medical Center
Director, Cardiovascular Devices Unit
Duke Clinical Research Institute