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
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
• Modest Consulting Fees
• Significant Consulting Fees
• Significant Consulting Fees
• Significant Consulting Fees
• Significant Consulting Fees
• Significant Consulting Fees
• Major Stock Shareholder/Equity
Company
• HCRI
• Boston Scientific
• Abbott Vascular
• Svelte Medical Systems, Inc.
• Janssen Research & Development LLC
• Sanofi-Aventis U.S. LLC
• Ablative Solutions, Inc.
Absorb BVS
Everolimus/PDLLA (1:1)
matrix coating
• 7 µm
• Conformal coating
• Controlled drug release similar
to Xience CoCr-EES
PLLA Backbone
• Semi-crystalline
Fully
Bioresorbable
• Circumferential sinusoidal rings
connected by linear links
• Strut thickness 150 µm
• Platinum markers in each end
ring
Phases of Absorb
Functionality
Revascularization
Restoration
Resorption
Mechanical Support
Mass loss
Drug Elution
1
3
6
Months
Oberhauser JP et al. EuroInt 2009;5:F15-22
24
Metallic DES vs. Absorb BVS
Representative Human images at 5 Years
Metallic DES1
1Atherosclerosis
2
Absorb-Treated Artery2
2014;237:23e29
Images courtesy of S Windecker, ABSORB Cohort B 5 Yrs
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
ABSORB III Study Design
Prospective, multicenter, single-blind, trial
~2,000 patients randomized
2:1 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
193 Enrolling Centers
U.S.
Australia
Top Enrollers (N patients)
1. Dr. Metzger (76)
8. Dr. DeGregorio (38)
15. Dr. Waksman (26)
Holston Valley Wellmont Medical
Center
Englewood Hospital and Medical
Center
MedSTAR Washington Hospital
Center
2. Dr. Caputo (52)
St. Joseph's Hospital Health
Center
9. Dr. Cannon (36)
16. Dr. Abbas (24)
Northern Michigan Hospital
William Beaumont Hospital
3. Dr. Rizik (49)
10. Drs. Cambier & Stein (35)
Scottsdale Healthcare
Morton Plant Hospital,
17. Dr. Zidar (24)
Rex Hospital, Inc
4. Dr. Teirstein (45)
11. Dr. Newman (34)
18. Dr. Dearing (24)
Scripps Green Hospital
WakeMed
Thomas Hospital
5. Dr. Litt (42)
12. Dr. Feldman (31)
19. Dr. Williams (23)
Baptist Medical Center
Munroe Regional Medical Center
Presbyterian Hospital
6. Dr. Kini (41)
13. Dr. Broderick (28)
Mount Sinai Medical Center
The Christ Hospital
Baylor Jack and Jane Hamilton
Heart and Vascular Hospital
7. Dr. Kabour (41)
14. Dr. Jain (28)
21. Dr. Moses (23)
Mercy St. Vincent Medical Center
Washington Hospital, Fremont, CA
Columbia University Medical Center
20. Dr. Choi (23)
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
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)
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 0.025 (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%
Key Patient Eligibility Criteria
• >18 years old
• Evidence of myocardial ischemia (stable/unstable/postinfarction 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)
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
ABSORB
N=1312
99.2% Complete
N=6 lost to follow-up
N=3 withdrew consent
12-month Follow-up
Xience
N=677
98.7% Complete
Baseline Characteristics
Absorb
(N=1322)
Xience
(N=686)
p-value
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
10.5%
11.2%
0.60
Prior MI
21.5%
22.0%
0.79
Prior coronary intervention
38.7%
38.0%
0.75
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
Characteristic
Age (mean)
Insulin-treated
Baseline Lesion Characteristics (QCA)
Absorb
(N=1322)
(L=1385)
Xience
(N=686)
(L=713)
p-value
68.7%
72.5%
0.08
1.0 ± 0.2
1.0 ± 0.2
0.38
One
95.1%
96.1%
0.32
Two
4.8%
3.9%
0.36
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
0.36
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
Characteristic
ACC/AHA lesion class B2/C
# of target lesions treated
Target lesion
RVD <2.25 mm
N= number of subjects
L= number of lesions
Procedural Characteristics
Absorb
(N=1322)
(L=1385)
Xience
(N=686)
(L=713)
p-value
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%
<0.001
Intravascular imaging guidance
11.2%
10.8%
0.81
42.2 ± 23.1
38.3 ± 20.9
<0.001
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
15.4 ± 3.0
15.4 ± 3.2
0.83
Characteristic
Per Subject
Procedure duration (min)
Per Lesion
Maximum device/balloon pressure (atm.)
N= number of subjects
L= number of lesions
Post-procedural QCA
Absorb
(N=1322)
(L=1385)
Xience
(N=686)
(L=713)
p-value
2.70 ± 0.45
2.68 ± 0.47
0.33
MLD
2.37 ± 0.40
2.49 ± 0.40
<0.0001
Acute gain
1.45 ± 0.45
1.59 ± 0.44
<0.0001
%DS
11.6 ± 8.77
6.4 ± 8.91
<0.0001
MLD
2.15 ± 0.41
2.14 ± 0.43
0.58
Acute gain
1.23 ± 0.46
1.24 ± 0.44
0.50
%DS
20.0 ± 7.94
19.8 ± 8.20
0.55
Measurement
RVD
In-Device
In-Segment
N= number of subjects
L= number of lesions
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
Successful withdrawal of delivery system and final in-scaffold/stent DS <30% (QCA)
No in-hospital (maximum 7 days) TLF
Antiplatelet Agent Usage
Absorb
(N=1322)
Xience
(N=686)
p-value
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
99.3%
99.3%
1.00
P2Y12 inhibitor
99.0%
99.1%
0.81
Clopidogrel
68.3%
72.0%
0.09
Prasugrel
20.7%
17.5%
0.08
Ticagrelor
11.8%
10.6%
0.44
Aspirin usage
98.6%
99.0%
0.43
P2Y12 inhibitor
94.4%
95.0%
0.55
Clopidogrel
67.5%
72.2%
0.03
Prasugrel
17.9%
14.0%
0.03
Ticagrelor
9.0%
8.9%
0.94
Aspirin usage
95.8%
95.8%
0.94
At index procedure
Aspirin
At 30 days
At 1 year
Primary Endpoint
1 Year TLF
Non-inferiority margin
= 4.5%
1-Year TLF
ABSORB vs. Xience
7.8% (102/1313) vs. 6.1% (41/677)
Difference = 1.7% [-0.5%, 3.9%]
PNI = 0.007
-1
0
1
2
3
4
% Difference (ABSORB - Xience)
5
TLF (%)
Target Lesion Failure
100%
20%
80%
15%
60%
10%
40%
5%
20%
0%
Absorb BVS (n=1322)
Xience CoCr-EES (n=686)
Diff [95% CI] =
1.7% [-0.5% to 3.9%]
Psuperiority=0.16
7.7%
6.0%
0
1
2
3
4
5
6
7
8
9 10 11 12 13
0%
0
1
No. at Risk:
Absorb
1322 1254
Xience
686 661
2
3
4
5
6
7
8
9
10
11
12
13
Months Post Index Procedure
1230
651
1218
643
1196
634
1-Year TLF: Subgroup analysis
Subgroup
Age ≥64 years
Absorb
(N=1322)
8.1%
Xience
(N=686)
5.9%
RR
(95% CI)
Age <64 years
7.4%
6.2%
1.19 (0.72-1.97)
Female
8.5%
7.4%
1.16 (0.64-2.08)
Male
7.4%
5.5%
1.36 (0.88-2.10)
Diabetes
10.7%
9.1%
1.18 (0.71-1.95)
No diabetes
6.3%
4.6%
1.38 (0.85-2.24)
Unstable angina/recent MI
Stable CAD
Single TL/TV treated
6.5%
8.3%
7.7%
6.6%
5.8%
5.8%
0.98 (0.50-1.90)
1.42 (0.94-2.15)
1.32 (0.92-1.89)
Dual TL/TV treated
9.4%
11.5%
0.81 (0.22-3.01)
Clopidogrel
Prasugrel or ticagrelor
ACC/AHA class A or B1
8.0%
7.1%
6.8%
6.8%
4.3%
2.2%
1.17 (0.77-1.78)
1.63 (0.82-3.25)
3.05 (1.08-8.60)
ACC/AHA class B2 or C
8.2%
7.5%
1.10 (0.75-1.61)
Lesion length <11.75 mm
7.9%
4.8%
1.64 (0.95-2.83)
Lesion length ≥11.75 mm
7.7%
7.3%
1.06 (0.67-1.67)
RVD <2.63 mm
9.8%
7.8%
1.27 (0.82-1.94)
RVD ≥2.63 mm
5.7%
4.3%
1.34 (0.73-2.44)
0.1
Favors Absorb
1.0
Relative Risk
(95% CI)
1.37 (0.84-2.23)
10
Favors Xience
p-value
(interaction)
0.69
0.68
0.68
0.35
0.50
0.43
0.07
0.23
0.90
1-Year TLF Components
10
1-Year TLF (%)
8
7.8
Absorb (N=1322)
Xience (N=686)
P=0.16
P=0.18
6.1
6.0
6
4.6
P=0.50
4
3.0
2.5
P=0.29
2
0.6
0.1
0
TLF
Cardiac death
TV-MI
ID-TLR
Myocardial Infarction to 1 Year
10
Absorb (N=1322)
Xience (N=686)
P=0.28
8
P=0.40
P=0.18
1-Year MI (%)
6.9
P=0.31
6.1
6
5.6
6.0
5.3
5.2
4.6
4.3
4
P=0.56
P=0.35
0.8
0.7
2
0.4
0.3
0
All MI
All Q-MI
All NQ-MI
TV MI
TV Q-MI
TV NQ-MI
Peri-Procedural MI by Definition
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%
0.2
0.75
>8x ULN
1.3%
1.3%
0.0
0.96
>10x ULN
0.9%
1.2%
-0.3
0.58
SCAI definition*
0.9%
1.2%
-0.3
0.58
CK-MB threshold
*>10x ULN or >5x ULN with new Q waves or new persistent LBBB
J Am Coll Cardiol 2013;62:1563-70
Device Thrombosis to 1 Year
Absorb
(N=1322)
Xience
(N=686)
p-value
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%
0.74%
0.21
- Probable (1 year )
0.15%
0.00%
0.55
Device Thrombosis (def*/prob)
*One “definite ST” in the Absorb arm by ITT
was in a pt that was treated with Xience
1-Year Device Thrombosis
Subgroup
Age ≥64 years
Age <64 years
Female
Male
Diabetes
No diabetes
Unstable angina/recent MI
Stable CAD
Single TL/TV treated
Dual TL/TV treated
Clopidogrel
Prasugrel or ticagrelor
ACC/AHA class A or B1
ACC/AHA class B2 or C
Lesion length <11.75 mm
Lesion length ≥11.75 mm
RVD <2.63 mm
RVD ≥2.63 mm
Absorb
(N=1322)
1.8%
1.2%
1.6%
1.5%
3.2%
0.8%
1.0%
1.7%
1.6%
0.0%
1.8%
0.8%
0.8%
1.9%
1.4%
1.7%
2.3%
0.8%
Xience
(N=686)
0.6%
0.9%
2.0%
0.2%
1.4%
0.4%
0.6%
0.8%
0.8%
0.0%
0.7%
0.9%
0.6%
0.8%
0.9%
0.6%
0.9%
0.6%
RR
(95% CI)
0.1 1
Favors Absorb
Relative Risk
(95% CI)
3.22 (0.73-14.32
1.33 (0.36-4.99)
0.79 (0.23-2.78)
7.21 (0.95-54.63)
2.34 (0.67-8,13)
1.79 (0.37-8.56)
1.88 (0.21-16.74)
2.16 (0.73-6.42)
2.09 (0.79-5.55)
2.69 (0.78-9.24)
0.96 (0.18-5.20)
1.36 (0.14-12.98)
2.32 (0.79-6.87)
1.58 (0.43-5.78)
2.82 (0.63-12.67)
2.65 (0.77-9.07)
1.28 (0.25-6.54)
10 100
Favors Xience
p-value
(interaction)
0.38
0.07
0.78
0.91
n/a
0.33
0.67
0.56
0.48
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
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
Outcomes by QCA RVD 2.25 mm
1-Year Events (%)
20%
RVD <2.25 mm
RVD ≥2.25 mm
(median 2.09 mm)
(median 2.74 mm)
Absorb
15%
Xience
TLF: Pint diff = 0.31
ST: Pint diff = 0.12
12.9%
10%
8.3%
6.7%
5.5%
4.6%
5%
1.5%
0.9% 0.6%
0%
TLF
ST
TLF
ST
# Events:
31
11
11
2
71
30
9
3
# Risk:
241
133
238
133
1067
542
1058
540
Median based on pooled Absorb and Xience
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 higherrisk 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
Summary and Conclusions (1)
• ABSORB BVS was non-inferior to Xience CoCrEES 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
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