The 4-year Clinical Outcomes of the ABSORB II Trial:

First Randomized Comparison between the Absorb

Everolimus Eluting Bioresorbable Vascular Scaffold
and the XIENCE Everolimus Eluting Stent

Bernard Chevalier
Institut Jacques Cartier, Massy, France

Patrick W. Serruys
Imperial College, London, UK
Erasmus University MC, Netherlands

on behalf of the ABSORB II Investigators

 Presentor Disclosures

Bernard Chevalier was a Consultant for Abbott Vascular

and is currently consultant for Biotronik, Colibri, Cordis,
Medtronic, Terumo.

Patrick Serruys is a Member of the International

Advisory Board of Abbott Vascular
 ABSORB II Study Design
501 subjects
Randomized 2:1 Absorb BVS:XIENCE / 46 sites (Europe and New Zealand)

Clinical Follow-Up

30d 6m 12m 24m 36m 48m 60m

QoL follow-up
Angio, IVUS follow-up
MSCT follow-up (Absorb arm only)*
Study Objective Randomized against XIENCE control. First Patient In: 28-Nov-2011
Vasomotion assessed by change in Mean Lumen Diameter between pre-
Co-primary
and post-nitrate at 3 years (superiority)
Endpoints
Minimum Lumen Diameter (MLD) at 3 years post nitrate minus MLD
36 months
post procedure post nitrate (non-inferiority, reflex to superiority)
Up to 2 de novo lesions in different epicardial vessels
Treatment
Planned overlapping allowed in lesions ≤ 48 mm
Device diameters: 2.5, 3.0, 3.5 mm
Device Sizes
Device lengths: 12 (3.5 mm diameter only), 18, 28 mm

The ABSORB II study is sponsored by Abbott Vascular. [NCT01425281]

 Characteristics of Patients at Baseline
Absorb Xience
95% CI
335 pts 166 pts
Age (year) mean ±SD 61.5 ± 10.0 60.9 ± 10.0 N.S.
Male % 75.5 79.5 N.S.
Current Tobacco Use % 23.6 21.7 N.S.
Hypertension % 69.0 71.7 N.S.
Dyslipidemia % 75.2 80.1 N.S.
All Diabetes Mellitus % 23.9 24.1 N.S.
Diabetes Mellitus Insulin Dependent % 6.6 8.4 N.S.
Family History of Premature CAD % 36.6 41.3 N.S.
Prior Intervention in Target Vessel % 11.7 8.9 N.S.
Prior MI % 28.0 28.9 N.S.
Stable Angina % 63.9 64.5 N.S.
Unstable Angina % 20.3 22.3 N.S.
Silent Ischemia % 12.5 11.4 N.S.
Recent MI with normalized cardiac enzyme % 3.3 1.8 N.S.
 Procedural Assessment Pre and Post Procedure
Absorb Xience p
364 Lesions 182 Lesions value

Procedural Details Per Lesion

Balloon dilatation prior to device implantation % 100 98.9 0.11

Planned overlap with the same type of device % 15.4 11.0 0.16

Unplanned/bailout implantation “same” % 3.8 6.0 0.25

Nominal size of study device mm 3.01 3.05 0.10

Balloon dilatation after device implantation % 60.7 58.8 0.67

Nominal diameter of last balloon used mm 3.08 3.16 0.02

<
Maximum last balloon pressure used atm 14.23 15.03 0.01
<
Acute recoil post device implantation mm 0.19 0.19 0.85

Acute Clinical Device Success % 99.2 100 0.55

Acute Clinical Procedural Success % 96.1 98.8 0.16

 4-Year Patient Flowchart 311* and 154**
Intent To Treat patients still in
N=501 the study but 5
missed 3 yr FUP
Absorb BVS XIENCE
N=335 Baseline N=166
7 withdrawal 1 death
2 withdrawal
N=328 1-year N=163
4 death
3 withdrawal
1 LFU 3 withdrawal

N=320 2-year N=160

4 death
3 withdrawal 5 death, 1 LFU
2 LFU, 3 MV, 2 MV

2 death,
N=308* 3-year N=152** 1 death,
8 MV, 3 withdrawal 2 MV, 1 withdrawal
9 no consent, -3 still 11 no consent ,-2
in study but missed still in study but
3yr FUP missed 3yr FUP
N=289 N=139
4-year
(86%) (84%)
At 4 years patients with missing visits (MV) were confirmed as alive and well by site PI.
20 patients did not sign protocol amendment for 4 & 5 year follow-up
 Clinical Endpoints at 3 Years
Absorb Xience
Hierarchical 325 patients 161 patients
Relative Risk p value
Device-oriented composite endpoint
[DOCE] 10.5% 5.0% 2·11 [1·00, 4·44] 0·04

Cardiac death 0.9% 1.9% 0·50 [0·10, 2·43] 0·4

Target vessel MI 6.5% (21) 1.2% (2) 5·20 [1·23, 21·91] 0·01
Periprocedural MI* 4.0%(13) 1.2% (2) 3.22 [0.74, 14.10] 0.16
Spontaneous MI* 2.5% (8) 0% (0) NC [NC] 0.06
Clinically indicated TLR 3.1% (10) 1.9% (3) 1·65 [0·46, 5·92] 0·56
Patient-oriented composite endpoint
[POCE] 20.9% 24.2% 0·86 [0·61, 1·22] 0·4

All-cause death 2.5% 3.7% 0·66 [0·23, 1·87] 0·57

Any MI 7.7% 3.1% 2.48 [0.97, 6.35] 0.048

Any revascularization 10.8% 17.4% 0·62 [0·39, 0·98] 0.04

* Per extend historical MI definition

 Device oriented Composite Endpoint (DOCE)/
Target Lesion Failure (TLF)
25
BVS XIENCE
HR [95% CI]= 2.17 [1.01,4.69]
20 p=0.043 (Log rank test)
TLF per WHO (%)

15

10.4%
10

4.9%
5

0 180 360 540 720 900 1080 1260 1440 1620

Time Post Index Procedure (Days)

DoCE/TLF : Cardiac death, target-vessel myocardial infarction, and clinically
indicated target-lesion revascularisation (TLR)
 Device oriented Composite Endpoint (DOCE)/
Target Lesion Failure (TLF)
25 25
BVS XIENCE
20 HR [95% CI]= 1.44 [0.15,13.80]
HR [95% CI]= 2.04 [0.98,4.24] p=0.75 (Log rank test)
15
20 p=0.050 (Log rank test)
10
Δ = 0.3%
TLF per WHO (%)

5 1.0%
15 0.7%
0
1152 1260 1440 1620

11.1%
10

5.6%
5

0 180 360 540 720 900 1080 1260 1440 1620

Time Post Index Procedure (Days)

DoCE/TLF : Cardiac death, target-vessel myocardial infarction, and clinically
indicated target-lesion revascularisation (TLR)
 Patient oriented Composite Endpoint (PoCE)/DMR
30
BVS XIENCE
POCE / DMR per WHO (%)

HR [95% CI]= 0.85 [0.58,1.27] 24.2%

25
p=0.43 (Log rank test)

20 20.9%

15

10

0 180 360 540 720 900 1080 1260 1440 1620

Time Post Index Procedure (Days)

PoCE=DMR: All Death, all Myocardial infarction, and all Revascularisation
 Patient oriented Composite Endpoint (PoCE)/DMR
30
BVS XIENCE
POCE / DMR per WHO (%)

HR [95% CI]= 0.90 [0.61,1.33] 24.9%

25
p=0.60 (Log rank test)
22.9%
20

15 30

25
HR [95% CI]= 3.14 [0.71,13.93]
20 p=0.11 (Log rank test)
10
15

10 Δ = 2.9%
5 5 4.3%
0
1.4%
1152 1260 1440 1620
0

0 180 360 540 720 900 1080 1260 1440 1620

Time Post Index Procedure (Days)

PoCE=DMR: All Death, all Myocardial infarction, and all Revascularisation
 4-year Clinical Outcomes Composite Endpoints
Absorb BVS XIENCE
p value
N=335 N=166

PoCE (%) 23.6 26.7 0.4682

MACE (%) 12.4 8.0 0.1545

DoCE, TLF (%) 11.5 6.0 0.0628

TVF (%) 14.0 14.0 0.9970

PoCE (Patient oriented Composite Endpoint):
All death, all myocardial infarction, and all revascularisation
MACE (Major Adverse Cardiac Events):
Cardiac death, all myocardial infarction, and clinically indicated target-lesion revascularisation (TLR)
DoCE (Device oriented Composite Endpoint)/ TLF (Target Lesion Failure):
Cardiac death, target-vessel myocardial infarction, and clinically indicated target-lesion revascularisation (TLR)
TVF (Target Vessel Failure):
Cardiac death, all myocardial infarction, clinically indicated target-vessel revascularisation (TVR)
Clinical Outcomes Non Hierarchical Events
3-4 years
Absorb
XIENCE
BVS p value
N=166
N=335
Death* n(%) 2(0.7) 1(0.7) 1.0000
Cardiac 1(0.3) 1(0.7) 0.5408
Vascular 0(0.0) 0(0.0) 1.0000
Non-cardiovascular 1(0.3) 0(0.0) 1.0000
Myocardial Infarction n(%) 1(0.3) 0(0.0) 1.0000
Q-wave 0(0.0) 0(0.0) 1.0000
Non Q-wave 1(0.3) 0(0.0) 1.0000
All Revascularization* n(%) 10(3.3) 1(0.7) 0.1142
All TLR 2(0.7) 0(0.0) 1.0000
All NTL-TVR 4(1.3) 0(0.0) 0.3102
All NTVR 6(2.0) 1(0.7) 0.4373
*Per ARC. Cutlip et al., Circulation. 2007;115:2344-2351
 Definite/Probable Scaffold/Stent Thrombosis*
25
BVS XIENCE
HR [95% CI]= NA [NA]
20 p=0.033 (Log rank test)
ARCST DPr (%)

15

10

5
2.8%

0.0%
0

0 180 360 540 720 900 1080 1260 1440 1620

Time Post Index Procedure (Days)

*Per ARC. Cutlip et al., Circulation. 2007;115:2344-2351
 Definite/Probable Scaffold/Stent Thrombosis*
25
BVS XIENCE No stent/scaffold thrombosis between 3
HR [95% CI]= NA [NA] and 4 years”

20 p=0.033 (Log rank test) 25

20
HR [95% CI]= NA [NA]
ARCST DPr (%)

15 15 p= (Log rank test)

10

5 0.0%
10 0.0%
0
1152 1260 1440 1620

5
2.8%

0.0%
0

0 180 360 540 720 900 1080 1260 1440 1620

Time Post Index Procedure (Days)

*Per ARC. Cutlip et al., Circulation. 2007;115:2344-2351
 Scaffold/Stent Thrombosis
4 years
Absorb BVS XIENCE
p value
N=335 N=166

Definite ST* 0-1488 days (%) 2.6 0.0 0.0583

Acute/sub-acute (0-30 days 0.6 0.0 1.0000
Late (31-365 days) 0.0 0.0 1.0000
Very late (365 – 14888 days) 1.8 0.0 0.1851
Very late between 3 – 4 year follow-up (N) 0 0 NA
Definite/Probable ST* 0-1488 days(%) 3.0 0.0 0.0347
Acute/sub-acute (0-30 days) 0.6 0.0 1.000
Late (31-365 days) 0.3 0.0 1.0000
Very late (365 – 1488 days) 1.8 0.0 0.1851
Very late between 3 – 4 year follow-up (N) 0 0 NA

*Per ARC. Cutlip et al., Circulation. 2007;115:2344-2351

 4-year Summary of Subjects on DAPT at 4 Years
Absorb BVS XIENCE
p value
N= 86 N= 35
Hierarchical PoCE*, % 37.2 42.9 0.5633
All death (Non-hierarchical) 0.0 0.0 1.0000
All MI (Non-hierarchical) 10.5 5.7 0.5076
All revascularization (Non-hierarchical) 33.7 42.9 0.3435
Hierarchical DoCE* or TLF, % 17.4 5.7 0.1472
Cardiac death (Non-hierarchical) 0.0 0.0 1.0000
TV-MI (Non-hierarchical) 10.5 0.0 0.0578
CI-TLR (Non-hierarchical) 12.8 5.7 0.3429

Per Protocol Myocardial Infarction (MI):
• Q wave MI
Development of new, pathological Q wave on the ECG.
• Non-Q wave MI
Elevation of CK levels to ≥ two times the upper limit of
normal (ULN) with elevated CK-MB in the absence of
new pathological Q waves.
PoCE (Patient oriented Composite Endpoint)*:
All death, all myocardial infarction, and all
revascularisation.
DoCE (Device oriented Composite Endpoint)*/ TLF
(Target Lesion Failure):
Cardiac death, target-vessel myocardial infarction,
and clinically indicated target-lesion revascularisation
(TLR).

*Per ARC. Cutlip et al., Circulation. 2007;115:2344-2351

 Limitations
• The ABSORB II study was not powered for clinical
endpoints

• Patients in the ABSORB II Study were enrolled before

the current recommendations for scaffold
implantation
 Conclusions
• The Absorb scaffold polymer has been reported to be
completely bio-resorbed by 3 years. Between 3 and 4 years
follow up
– there were no ST events in the Absorb arm
– DOCE/TLF events were similar between Absorb and Xience
• In a trial which was not powered for clinical events, at 4 years
there were no statistically significant differences in the clinical
outcomes between the two arms:
– PoCE (all death, all MI and all revascularization)
Absorb BVS: 23.6% vs XIENCE: 26.7%, p=0.47
– DoCE/TLF (cardiac death, TV-MI and TLR)
Absorb BVS: 11.5% vs XIENCE: 6.0%, p=0.06
• The exploratory observations presented in this report are
hypothesis generating and need to be confirmed in larger
randomized trials such as ABSORB III and ABSORB IV