1. Everolimus-eluting Bioresorbable Vascular Scaffolds in Patients with Coronary Artery Disease:
The ABSORB III trial
Dean J. Kereiakes, MD, Stephen G. Ellis, MD, D. Christopher Metzger, MD, Ronald P. Caputo, MD, David G. Rizik, MD, Paul S. Teirstein, MD, Marc R. Litt, MD, Annapoorna Kini, MD, Ameer Kabour, MD, Steven O. Marx, MD, Jeffrey J. Popma, MD, Robert McGreevy, PhD, Zhen Zhang, PhD, Charles Simonton, MD and Gregg W. Stone, MD for the ABSORB III Investigators

2. Disclosure Statement of Financial Interest
Within the past 12 months, I or my spouse/partner have had a financial interest/arrangement or affiliation with the organization(s) listed below.
Affiliation/Financial Relationship
Company
Modest Consulting Fees
Significant Consulting Fees
Major Stock Shareholder/Equity
HCRI
Boston Scientific
Abbott Vascular
Svelte Medical Systems, Inc.
Janssen Research & Development LLC
Sanofi-Aventis U.S. LLC
Ablative Solutions, Inc.

3. Absorb BVS Fully Bioresorbable Everolimus/PDLLA (1:1) matrix coating
Conformal coating
Controlled drug release similar to Xience CoCr-EES
PLLA Backbone
Semi-crystalline
Circumferential sinusoidal rings connected by linear links
Strut thickness 150 µm
Platinum markers in each end ring
Fully
Bioresorbable

4. Oberhauser JP et al. EuroInt 2009;5:F15-22
Phases of Absorb
Functionality
Revascularization
Restoration
Resorption
Mechanical Support
Mass loss
Drug Elution 1 3 6
Months 24
Oberhauser JP et al. EuroInt 2009;5:F15-22 4

5. Metallic DES vs. Absorb BVS
Representative Human images at 5 Years
Metallic DES1
Absorb-Treated Artery2
1Atherosclerosis 2014;237:23e29
2 Images courtesy of S Windecker, ABSORB Cohort B 5 Yrs

6. Absorb Program Objectives A Series of Randomized Trials Designed to:
Demonstrate similar (non-inferior) results with ABSORB BVS compared to Xience CoCr-EES at 1 year
Demonstrate superior results with ABSORB BVS compared to Xience CoCr-EES between 1 and 5 years

7. ABSORB III Study Design Prospective, multicenter, single-blind, trial
~2,000 patients randomized :1 Absorb BVS vs. Xience CoCr-EES
Clinical follow-up:
30 d
6 mo
12 mo
24 mo
36 mo
48 mo
60 mo
No routine angiographic follow-up 7

8. 193 Enrolling Centers
U.S.
Australia

9. Top Enrollers (N patients)
1. Dr. Metzger (76)
Holston Valley Wellmont Medical Center
8. Dr. DeGregorio (38)
Englewood Hospital and Medical Center
15. Dr. Waksman (26)
MedSTAR Washington Hospital Center
2. Dr. Caputo (52)
St. Joseph's Hospital Health Center
9. Dr. Cannon (36)
Northern Michigan Hospital
16. Dr. Abbas (24)
William Beaumont Hospital
3. Dr. Rizik (49)
Scottsdale Healthcare
10. Drs. Cambier & Stein (35)
Morton Plant Hospital,
17. Dr. Zidar (24)
Rex Hospital, Inc
4. Dr. Teirstein (45)
Scripps Green Hospital
11. Dr. Newman (34)
WakeMed
18. Dr. Dearing (24)
Thomas Hospital
5. Dr. Litt (42)
Baptist Medical Center
12. Dr. Feldman (31)
Munroe Regional Medical Center
19. Dr. Williams (23)
Presbyterian Hospital
6. Dr. Kini (41)
Mount Sinai Medical Center
13. Dr. Broderick (28)
The Christ Hospital
20. Dr. Choi (23)
Baylor Jack and Jane Hamilton Heart and Vascular Hospital
7. Dr. Kabour (41)
Mercy St. Vincent Medical Center
14. Dr. Jain (28)
Washington Hospital, Fremont, CA
21. Dr. Moses (23)
Columbia University Medical Center

10. Study Leadership Principal Investigators
Dean Kereiakes, MD, The Christ Hospital, Cincinnati, OH
Stephen G. Ellis, MD, Cleveland Clinic, Cleveland, OH
Study Chairman
Gregg W. Stone, MD, Columbia University Medical Center, NY, NY
Clinical Events Committee
Cardiovascular Research Foundation, New York, NY Steven Marx, MD, chair
Angiographic Core Laboratory
Beth Israel Deaconess Medical Center, Boston, MA Jeff Popma, MD, director
Data Safety Monitoring Board
Axio Research, Seattle, WA; Robert N. Piana, MD, chair
Sponsor
Abbott Vascular, Santa Clara, CA 10

11. Major Endpoints at 1 Year
Primary Endpoint: Target Lesion Failure (non-inferiority)
Cardiac death, or
Myocardial infarction attributed to the target vessel (TV-MI), or
Peri-procedural MI: CK-MB >5x ULN w/i 48 hours
Ischemia-driven target lesion revascularization (ID-TLR)
Powered Secondary Endpoints (superiority)
Angina
All revascularization
Ischemia-driven target vessel revascularization (ID-TVR) 11

12. Maximum observed difference in order to pass non-inferiority = 2%
Statistical Design
Primary Endpoint
Non-inferiority analysis for TLF at 1 year with the following assumptions:
1-year TLF rate of 7%
Non-inferiority margin of 4.5%
“Putative placebo”, preserving ≥ 50% of the treatment effect of Xience vs. BMS
1-sided alpha of (equivalent to 2-sided 0.05)
95% 1-year follow-up
2000 subjects → 96% power
Maximum observed difference in order to pass non-inferiority = 2% 12

13. Key Patient Eligibility Criteria
>18 years old
Evidence of myocardial ischemia (stable/unstable/post- infarction angina or silent ischemia)
No elevation of CK-MB
1 or 2 de novo target lesions in up to 2 native coronary arteries (max 1 lesion per artery)
Diameter stenosis ≥50% and <100% with TIMI flow ≥1
If <70%, abnormal functional test (including FFR ≤0.80), unstable angina or post-infarct angina
RVD ≥2.50 mm and ≤3.75 mm (site-determined)
Lesion length ≤24 mm (site-determined) 13

14. Study Flow and Follow-up
Randomized 2:1
N=2008 (ITT)
ABSORB 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
ABSORB
N=1312
Xience
N=677
12-month Follow-up
99.2% Complete
98.7% Complete

15. Baseline Characteristics
Absorb
(N=1322)
Xience
(N=686)
p-value
Age (mean)
63.5 ±10.6
63.6±10.3
0.75
Male
70.7%
70.1%
0.80
Race (Caucasian)
87.1%
88.3%
0.44
Current tobacco use
21.3%
20.7%
0.77
Hypertension
84.9%
85.0%
0.95
Dyslipidemia
86.2%
86.3%
0.97
Diabetes
31.5%
32.7%
0.60
Insulin-treated
10.5%
11.2%
Prior MI
21.5%
22.0%
0.79
Prior coronary intervention
38.7%
38.0%
Stable angina
57.3%
60.8%
0.13
Unstable angina
26.9 %
24.5%
0.25
Silent ischemia
10.0%
10.2%
0.88
Single vessel disease
69.5%
67.2%
0.29

16. Baseline Lesion Characteristics (QCA)
Absorb
(N=1322)
(L=1385)
Xience
(N=686)
(L=713)
p-value
ACC/AHA lesion class B2/C
68.7%
72.5%
0.08
# of target lesions treated
1.0 ± 0.2
0.38
One
95.1%
96.1%
0.32
Two
4.8%
3.9%
0.36
Target lesion
LAD
44.5%
42.2%
0.31
RCA
29.2%
27.2%
0.35
Circumflex
26.2%
30.6%
0.03
Lesion length, mm
12.60 ± 5.41
13.12 ± 5.82
0.05
RVD, mm
2.67 ± 0.45
2.65 ± 0.46
RVD <2.25 mm
18%
19%
0.39
MLD, mm
0.92 ± 0.37
0.90 ± 0.34
0.11
%DS
65.3 ± 12.5
65.9 ± 11.7
0.24
N= number of subjects
L= number of lesions

17. Procedural Characteristics
Absorb
(N=1322)
(L=1385)
Xience
(N=686)
(L=713)
p-value
Per Subject
Bivalirudin use
60.7%
58.7%
0.39
GP IIb/IIIa inhibitor use
10.1%
12.4%
0.11
Only unassigned devices implanted
4.4%
0.6%
<0.001
Unplanned overlapping devices
6.2%
8.5%
0.06
Post-dilatation performed
65.5%
51.2%
Intravascular imaging guidance
11.2%
10.8%
0.81
Procedure duration (min)
42.2 ± 23.1
38.3 ± 20.9
Per Lesion
Total study device length (mm)
20.5 ± 7.2
20.7 ± 9.0
0.56
Max device/balloon diameter (mm)
3.18 ± 0.43
3.12 ± 0.45
0.007
Max device/balloon to vessel diameter ratio
1.21  0.15
1.19  0.14
0.05
Maximum device/balloon pressure (atm.)
15.4 ± 3.0
15.4 ± 3.2
0.83
N= number of subjects
L= number of lesions

18. Post-procedural QCA Measurement Absorb (N=1322) (L=1385) Xience
p-value
RVD
2.70 ± 0.45
2.68 ± 0.47
0.33
In-Device
MLD
2.37 ± 0.40
2.49 ± 0.40
<0.0001
Acute gain
1.45 ± 0.45
1.59 ± 0.44
%DS
11.6 ± 8.77
6.4 ± 8.91
In-Segment
2.15 ± 0.41
2.14 ± 0.43
0.58
1.23 ± 0.46
1.24 ± 0.44
0.50
20.0 ± 7.94
19.8 ± 8.20
0.55 .
N= number of subjects
L= number of lesions

19. Acute Success Absorb (N=1322) (L=1385) Xience (N=686) (L=713) p-value
Device Success
94.3%
99.3%
<0.0001
Procedural Success
94.6%
96.2%
0.12
Device Success (lesion basis)
Successful delivery and deployment of study scaffold/stent at intended target lesion
Successful withdrawal of delivery system and final in-scaffold/stent DS <30% (QCA)
Procedure Success (patient basis)
Successful delivery and deployment of at least one study scaffold/stent at intended target lesion
No in-hospital (maximum 7 days) TLF

20. Antiplatelet Agent Usage
Absorb
(N=1322)
Xience
(N=686)
p-value
At index procedure
P2Y12 inhibitor
99.0%
98.8%
0.70
Clopidogrel
62.6%
64.7%
0.34
Prasugrel
21.8%
19.5%
0.24
Ticagrelor
14.8%
14.9%
0.94
Aspirin
99.3%
1.00
At 30 days
99.1%
0.81
68.3%
72.0%
0.09
20.7%
17.5%
0.08
11.8%
10.6%
0.44
Aspirin usage
98.6%
0.43
At 1 year
94.4%
95.0%
0.55
67.5%
72.2%
0.03
17.9%
14.0%
9.0%
8.9%
95.8%

22. Months Post Index Procedure
Target Lesion Failure
100%
Absorb 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:
Absorb
1322
1254
1230
1218
1196
Xience
686
661
651
643
634

26. Peri-Procedural MI by Definition
CK-MB threshold
Absorb
(N=1322)
Xience
(N=686)
Difference
p-value
>3x ULN
6.8%
6.6%
0.2
0.89
>5x ULN (protocol)
3.0%
2.8%
0.75
>8x ULN
1.3%
0.0
0.96
>10x ULN
0.9%
1.2%
-0.3
0.58
SCAI definition*
*>10x ULN or >5x ULN with new Q waves or new persistent LBBB
J Am Coll Cardiol 2013;62:

27. Device Thrombosis to 1 Year
Absorb
(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 Absorb arm by ITT
was in a pt that was treated with Xience

28. 1-Year Device Thrombosis
Subgroup
Absorb
(N=1322)
Xience
(N=686) RR
(95% CI)
Relative Risk
p-value (interaction)
Age ≥64 years
1.8%
0.6%
3.22 (
0.38
Age <64 years
1.2%
0.9%
1.33 ( )
Female
1.6%
2.0%
0.79 ( )
0.07
Male
1.5%
0.2%
7.21 ( )
Diabetes
3.2%
1.4%
2.34 (0.67-8,13)
0.78
No diabetes
0.8%
0.4%
1.79 ( )
Unstable angina/recent MI
1.0%
1.88 ( )
0.91
Stable CAD
1.7%
2.16 ( )
Single TL/TV treated
2.09 ( )
n/a
Dual TL/TV treated
0.0% -
Clopidogrel
0.7%
2.69 ( )
0.33
Prasugrel or ticagrelor
0.96 ( )
ACC/AHA class A or B1
1.36 ( )
0.67
ACC/AHA class B2 or C
1.9%
2.32 ( )
Lesion length <11.75 mm
1.58 ( )
0.56
Lesion length ≥11.75 mm
2.82 ( )
RVD <2.63 mm
2.3%
2.65 ( )
0.48
RVD ≥2.63 mm
1.28 ( )
Favors Absorb
Favors Xience

29. Powered Secondary Endpoints
Absorb
(N=1322)
Xience
(N=686)
p-value
Angina
18.3%
18.4%
0.93
All Revascularization
9.1%
8.1%
0.50
ID-TVR
5.0%
3.7%
0.21

30. ABSORB III Very Small Vessel Analysis
ABSORB III eligibility criteria included vessels with RVD 2.5 mm – 3.75 mm (visual estimation)
The thicker struts of ABSORB may be of particular concern in very small vessels
Subgroup analysis was therefore performed in vessels with QCA RVD <2.25 mm vs. ≥2.25 mm (correlates with visual estimate ~2.5 mm)
~19% of patients had a target lesion with RVD <2.25 mm by QCA 30

31. Median based on pooled Absorb 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
1-Year Events (%)
# Events: 31 11 2 71 30 9 3
# Risk:
241
133
238
1067
542
1058
540
Median based on pooled Absorb and Xience

32. Limitations
ABSORB III enrolled patients with stable ischemic heart disease and stabilized ACS, and excluded specific complex lesions (e.g. CTO, LM, large bif); results may therefore not be generalizable to higher- risk patients and more complex disease
Underpowered for low frequency events
Results should be viewed in context that Xience was the control device which has been associated with the lowest rates of ST and other events
BVS is a first generation device and was used for the first time by most operators within this trial 32

33. Summary and Conclusions (1)
ABSORB BVS was non-inferior to Xience CoCr- EES for TLF at 1 year (primary endpoint met)
TLF components (cardiac death, TV-MI, ID-TLR) were not significantly different between devices
Angina, all revascularization and ID-TVR were similar between devices
No statistically significant differences in device thrombosis were present 33

34. Summary and Conclusions (2)
The ABSORB III trial has demonstrated safety and efficacy of Absorb BVS at 1 year in patients with stable CAD and stabilized ACS
Longer term evaluation is ongoing to determine if ABSORB improves late outcomes compared to Xience 34