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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
• Modest Consulting Fees• Significant Consulting Fees• Significant Consulting Fees• Significant Consulting Fees• Significant 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.
Affiliation/Financial Relationship Company
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.
Everolimus/PDLLA (1:1) matrix coating
• 7 µm
• 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
FullyBioresorbable
Absorb BVS
Drug Elution
Mechanical Support
Mass loss
Oberhauser JP et al. EuroInt 2009;5:F15-22
1 6 243
Revascularization Restoration Resorption
Months
Phases of Absorb Functionality
1Atherosclerosis 2014;237:23e292 Images courtesy of S Windecker, ABSORB Cohort B 5 Yrs
Metallic DES1 Absorb-Treated Artery2
Metallic DES vs. Absorb BVSRepresentative Human images at 5 Years
Absorb Program ObjectivesA 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
30 d
6 mo
12 mo
24 mo
36 mo
48 mo
60 mo
Clinical follow-up:
Prospective, multicenter, single-blind, trial~2,000 patients randomized
2:1 Absorb BVS vs. Xience CoCr-EES
ABSORB III Study Design
No routine angiographic follow-up
U.S.
Australia
193 Enrolling Centers
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
Top Enrollers (N patients)
• Principal InvestigatorsDean Kereiakes, MD, The Christ Hospital, Cincinnati, OHStephen G. Ellis, MD, Cleveland Clinic, Cleveland, OH
• Study ChairmanGregg W. Stone, MD, Columbia University Medical Center, NY, NY
• Clinical Events CommitteeCardiovascular Research Foundation, New York, NY
Steven Marx, MD, chair
• Angiographic Core LaboratoryBeth Israel Deaconess Medical Center, Boston, MA
Jeff Popma, MD, director
• Data Safety Monitoring Board Axio Research, Seattle, WA; Robert N. Piana, MD, chair
• SponsorAbbott Vascular, Santa Clara, CA
Study Leadership
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)
Major Endpoints at 1 Year
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%
Primary Endpoint
Statistical Design
• >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)
Key Patient Eligibility Criteria
Randomized 2:1N=2008 (ITT)
ABSORB N=1322
ABSORBN=1312
Xience N=677
99.2% Complete 98.7% Complete
N=4 lost to follow-upN=6 withdrew consent
N=6 lost to follow-upN=3 withdrew consent
XienceN=686
12-month Follow-up
Study Flow and Follow-up
CharacteristicAbsorb
(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% 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
Baseline Characteristics
Characteristic
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 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 0.36
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
Baseline Lesion Characteristics (QCA)
N= number of subjectsL= number of lesions
Characteristic
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% <0.001
Intravascular imaging guidance 11.2% 10.8% 0.81
Procedure duration (min) 42.2 ± 23.1 38.3 ± 20.9 <0.001
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
Procedural Characteristics
N= number of subjectsL= number of lesions
Measurement
Absorb(N=1322)(L=1385)
Xience(N=686)(L=713) 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 <0.0001
%DS 11.6 ± 8.77 6.4 ± 8.91 <0.0001
In-Segment
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
Post-procedural QCA
N= number of subjectsL= number of lesions
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
Acute Success
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% 99.3% 1.00
At 30 days
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
At 1 year
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
Antiplatelet Agent Usage
-1 0 1 2 3 4 5
Non-inferiority margin = 4.5%
Difference = 1.7% [-0.5%, 3.9%]PNI = 0.007
% Difference (ABSORB - Xience)
Primary Endpoint1 Year TLF
1-Year TLFABSORB vs. Xience
7.8% (102/1313) vs. 6.1% (41/677)
No. at Risk:Absorb
TL
F (
%)
Xience
Months Post Index Procedure
20%
100%
80%
60%
40%
0%
0 1 2 3 4 5 6 7 8 9 10 11 12
1322686
1254661
1230651
1218643
1196634
13
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%0 1 2 3 4 5 6 7 8 9 10 11 13
7.7%6.0%
12
Target Lesion Failure
SubgroupAbsorb
(N=1322)Xience
(N=686)RR
(95% CI)Relative Risk
(95% CI)p-value
(interaction)Age ≥64 years 8.1% 5.9% 1.37 (0.84-2.23)
0.69Age <64 years 7.4% 6.2% 1.19 (0.72-1.97)
Female 8.5% 7.4% 1.16 (0.64-2.08)0.68
Male 7.4% 5.5% 1.36 (0.88-2.10)
Diabetes 10.7% 9.1% 1.18 (0.71-1.95)0.68
No diabetes 6.3% 4.6% 1.38 (0.85-2.24)
Unstable angina/recent MI 6.5% 6.6% 0.98 (0.50-1.90)0.35
Stable CAD 8.3% 5.8% 1.42 (0.94-2.15)
Single TL/TV treated 7.7% 5.8% 1.32 (0.92-1.89)0.50
Dual TL/TV treated 9.4% 11.5% 0.81 (0.22-3.01)
Clopidogrel 8.0% 6.8% 1.17 (0.77-1.78)0.43
Prasugrel or ticagrelor 7.1% 4.3% 1.63 (0.82-3.25)ACC/AHA class A or B1 6.8% 2.2% 3.05 (1.08-8.60)
0.07ACC/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)0.23
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)0.90
RVD ≥2.63 mm 5.7% 4.3% 1.34 (0.73-2.44)
0.1 1 10Favors Absorb Favors Xience
1-Year TLF: Subgroup analysis
1.0
1-Year TLF Components
TLF Cardiac death TV-MI ID-TLR0
2
4
6
8
10
7.8
0.6
6.0
3.0
6.1
0.1
4.6
2.5
Absorb (N=1322)Xience (N=686)
1-Y
ea
r T
LF
(%
)
P=0.16
P=0.29
P=0.18
P=0.50
All MI All Q-MI All NQ-MI TV MI TV Q-MI TV NQ-MI0
2
4
6
8
10
6.9
0.8
6.1 6.0
0.7
5.35.6
0.4
5.24.6
0.3
4.3
Absorb (N=1322)
Xience (N=686)
1-Y
ea
r M
I (%
)
P=0.18
P=0.35
P=0.31
P=0.28
P=0.56
P=0.40
Myocardial Infarction to 1 Year
CK-MB thresholdAbsorb
(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
Peri-Procedural MI by Definition
*>10x ULN or >5x ULN with new Q waves or new persistent LBBB J Am Coll Cardiol 2013;62:1563-70
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% 0.74% 0.21
- Probable (1 year ) 0.15% 0.00% 0.55
*One “definite ST” in the Absorb arm by ITT was in a pt that was treated with Xience
Device Thrombosis to 1 Year
1-Year Device Thrombosis
SubgroupAbsorb
(N=1322)Xience
(N=686)RR
(95% CI)Relative Risk
(95% CI)p-value
(interaction)Age ≥64 years 1.8% 0.6% 3.22 (0.73-14.32
0.38Age <64 years 1.2% 0.9% 1.33 (0.36-4.99)
Female 1.6% 2.0% 0.79 (0.23-2.78)0.07
Male 1.5% 0.2% 7.21 (0.95-54.63)
Diabetes 3.2% 1.4% 2.34 (0.67-8,13)0.78
No diabetes 0.8% 0.4% 1.79 (0.37-8.56)
Unstable angina/recent MI 1.0% 0.6% 1.88 (0.21-16.74)0.91
Stable CAD 1.7% 0.8% 2.16 (0.73-6.42)
Single TL/TV treated 1.6% 0.8% 2.09 (0.79-5.55)n/a
Dual TL/TV treated 0.0% 0.0% -
Clopidogrel 1.8% 0.7% 2.69 (0.78-9.24)0.33
Prasugrel or ticagrelor 0.8% 0.9% 0.96 (0.18-5.20)
ACC/AHA class A or B1 0.8% 0.6% 1.36 (0.14-12.98)0.67
ACC/AHA class B2 or C 1.9% 0.8% 2.32 (0.79-6.87)
Lesion length <11.75 mm 1.4% 0.9% 1.58 (0.43-5.78)0.56
Lesion length ≥11.75 mm 1.7% 0.6% 2.82 (0.63-12.67)
RVD <2.63 mm 2.3% 0.9% 2.65 (0.77-9.07)0.48
RVD ≥2.63 mm 0.8% 0.6% 1.28 (0.25-6.54)
0.1 1 10 100Favors Absorb Favors Xience
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
Powered Secondary Endpoints
• 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
ABSORB III Very Small Vessel Analysis
TLF ST TLF ST
-5%
0%
5%
10%
15%
20%
12.9%
4.6%6.7%
0.9%
8.3%
1.5%
5.5%
0.6%
Absorb Xience
RVD <2.25 mm(median 2.09 mm)
1-Y
ear
Eve
nts
(%
)
Median based on pooled Absorb and Xience
RVD ≥2.25 mm(median 2.74 mm)
Outcomes by QCA RVD 2.25 mm
# Events: 31 11 11 2 71 30 9 3
# Risk: 241 133 238 133 1067 542 1058 540
TLF: Pint diff = 0.31ST: Pint diff = 0.12
• 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
Limitations
• 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
Summary and Conclusions (1)
• 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
Summary and Conclusions (2)