1. Impact of Technique on Early and Late Outcomes Following Coronary Bioresorbable Scaffold Implantation: Analysis from the ABSORB trials
Gregg W. Stone, MD
On behalf of: Ashok Seth, Runlin Gao, John Ormiston, Alex Abizaid, Takeshi Kimura, Bernard Chevalier, Ori Ben-Yehuda, Ovidiu Dressler, Tom McAndrew, Yoshinobu Onuma, Steve G. Ellis, Dean J. Kereiakes, Patrick W. Serruys

2. Gregg W. Stone Disclosures
Study chairman for the Absorb clinical trial program (uncompensated)
Consultant to Reva

3. Bioresorbable Scaffold Outcomes: Background: Why technique may matter
The ABSORB BVS is a novel first generation technology, which compared to contemporary metallic DES, has thicker struts, different expansion characteristics, and loss of structural integrity during the active bioresorption process
The strongest predictors of thrombosis and restenosis with metallic DES are a small MSA, untreated significant edge dissections, and untreated residual disease
There is no reason to think these parameters would be less important with BVS
Acute malapposition, which may increase the likelihood of intraluminal scaffold dismantling, may be even more important to prevent with BVS than with metallic DES

4. Hypothetical Keys to Absorb Success: “P-S-P”
P: Prepare the Lesion (aggressively)
Pre-dilate with balloon:RVD ~1:1
For calcified lesions or those that won’t fully pre-dilate: cutting/scoring balloons or atherectomy
Don’t implant scaffold unless full balloon expansion is achieved
S: Size the Scaffold Correctly
Use guide catheter, pre-dilatation balloon, on-line QCA, or intravascular imaging (IVUS, OCT). Don’t undersize!
Strongly consider IV imaging if visual RVD <3 mm or 2.5 mm BVS planned; never implant scaffold if RVD <2.5 mm!
P: Post-Dilate All Cases (unless perfect by IV imaging)
With a NC balloon sized ≥1:1 (upsize 0.5 mm if possible, staying within the scaffold margins) to high pressure (≥18 atm)
But never >0.5 mm larger than scaffold nominal diameter

5. Impact of Technique on Absorb BVS Outcomes: Methods
The data from 2,973 Absorb BVS-treated patients from 4 prospective trials (ABSORB II, ABSORB China, ABSORB Japan and ABSORB III) and 1 registry study (ABSORB Extend) were pooled into a single database
Outcomes up to 3 years were assessed according to pre-specified definitions of optimal technique, adjusted for study (longest available FU used)
Cox proportional hazards regression was used to determine the independent predictors of TLF and ScT from 0-1 year, 1-3 years and 0-3 years 5

6. Impact of Technique on Absorb BVS Outcomes: Methods, cont
The following defns for “optimal technique” were pre- specified by the ABSORB trial PIs prior to data analysis:
Sizing: Lesion(s) w/baseline QCA RVD ≥ ≤3.75 mm
Pre-dilatation: Pre-dil with a balloon with nominal diameter ≥1:1 to the baseline QCA RVD
Post-dilatation defn 1: Post-dilatation with a NC balloon ≥16 atm with nominal diameter/QCA-RVD ratio ≥1.1:1 and ≤0.5 mm than the nominal scaffold diameter
Post-dilatation defn 2: Post-dilatation with a non-compliant balloon ≥18 atm with nominal diameter larger than the nominal scaffold diameter but not >0.5 mm larger 6

7. Impact of Technique on Absorb Outcomes: Multivariable analysis Candidate predictors for TLF
Technique: Optimal vessel sizing*; optimal pre-dilatation**; optimal post-dilatation defn 1† (alternatively optimal post-dilatation defn 2†)
Clinical: Age (years), male, diabetes, BMI, tobacco user, dyslipidemia, HTN, prior PCI, prior MI, SIHD vs ACS
Angiographic: 1 vs 2 treated lesions, QCA max lesion length, QCA %DS pre, mod/sev calcification, bifurcation, ACC/AHA B2/C lesion, LAD/LM
For a variable to be “present”, it must apply to all treated lesions. *QCA RVD ≥2.25 mm - ≤3.75 mm for all treated lesions; **Pre-dilatation performed in all lesions with a balloon to QCA RVD ratio ≥1:1; †Definition 1: Post-dilatation with a non-compliant balloon ≥16 atm with nominal diameter/QCA-RVD ratio ≥1.1:1 and ≤0.5 mm than the nominal scaffold diameter. Definition 2: Post-dilatation with a non-compliant balloon ≥18 atm with nominal diameter larger than the nominal scaffold diameter but not >0.5 mm larger. 7

8. Impact of Technique on Absorb Outcomes: Multivariable analysis Candidate predictors for ScT
Technique: Optimal vessel sizing*; optimal pre-dilatation**; optimal post-dilatation defn 1† (alternatively optimal post-dilatation defn 2†)
Clinical: Diabetes, SIHD vs ACS
Angiographic: 1 vs 2 treated lesions, QCA max lesion length, QCA %DS pre, mod/sev calcification, bifurcation, LAD/LM
For a variable to be “present”, it must apply to all treated lesions. *QCA RVD ≥2.25 mm - ≤3.75 mm for all treated lesions; **Pre-dilatation performed in all lesions with a balloon to QCA RVD ratio ≥1:1; †Definition 1: Post-dilatation with a non-compliant balloon ≥16 atm with nominal diameter/QCA-RVD ratio ≥1.1:1 and ≤0.5 mm than the nominal scaffold diameter. Definition 2: Post-dilatation with a non-compliant balloon ≥18 atm with nominal diameter larger than the nominal scaffold diameter but not >0.5 mm larger. 8

9. 5 ABSORB studies, 2973 BVS patients
BVS treated only
ABSORB II
ABSORB Japan
ABSORB China
ABSORB III
ABSORB Extend
ClinicalTrials.gov
NCT
NCT
NCT
NCT
NCT
Study type
Rand
Reg
N centers 46 38 24
193 56
N study vessels/pt
1 or 2
N study lesions/pt*
N BVS treated pts
335
266
238
1,322
812
N BVS treated lsns
364
275
251
1385
874
*If 2 lesions, in separate vessels

10. 5 ABSORB studies, 2973 BVS patients
BVS treated only
ABSORB II
ABSORB Japan
ABSORB China
ABSORB III
ABSORB Extend
Target lesion RVD (mm)
Max LD to 3.8 by online QCA
≥2.5 to ≤3.75
≥2.5 to ≤3.75
≥2.5 to ≤3.75
≥2.0 to ≤3.8
Target lesion length (mm)
≤48
≤24
≤28
Device overlap allowed
Yes
Bailout only
Routine angiographic FU
At 3 years
At 13 months
At 12 months No
Primary endpoint
Angio vasomotion at 3 years
TLF at 1 year
Angio in- segment late loss at 1 year
TLF at 1 year -
Total follow-up
5 years
3 years
Latest follow-up
2 years
1 year

11. Pooled Absorb Database PSP characteristics
Per lesion (unless otherwise noted)
ABSORB II
(N=335, NL=364)
ABSORB Japan
(N=266, NL=275)
ABSORB China
(N=238, NL=251)
ABSORB III
(N=1,322, NL=1,385)
ABSORB Extend
(N=812, NL=874)
Pooled
(N=2,973, NL=3,149)
RVD (mm)
2.59 ± 0.38
2.71 ± 0.45
2.81 ± 0.44
2.67 ± 0.45
2.65 ± 0.39
2.67 ± 0.43
<2.25
20.1%
15.3%
9.2%
17.8%
14.8%
16.3%
>3.75
0.3%
2.9%
2.0%
1.6%
0.8%
1.4%
Optimal RVD*
79.7%
81.8%
88.8%
80.6%
84.4%
82.3%
Per pt (all lsns)
78.2%
81.5%
88.2%
80.0%
83.6%
81.6%
Optimal pre-dil**
50.7%
63.5%
47.2%
72.3%
47.1%
60.1%
48.2%
63.4%
47.3%
71.6%
45.4%
59.2%
Opt post-dil, defn 1†
28.1%
27.3%
28.7%
22.3%
29.8%
26.0%
27.8%
27.4%
28.6%
21.9%
25.5%
Opt post-dil, defn 2†
8.8%
15.6%
15.9%
9.9%
16.7%
12.7%
8.7%
15.4%
16.0%
9.5%
16.6%
12.4%
For a variable to be “present”, it must apply to all treated lesions. *QCA RVD ≥2.25 mm - ≤3.75 mm for all treated lesions; **Pre-dilatation performed in all lesions with a balloon to QCA RVD ratio ≥1:1; †Definition 1: Post-dilatation with a non-compliant balloon ≥16 atm with nominal diameter/QCA-RVD ratio ≥1.1:1 and ≤0.5 mm than the nominal scaffold diameter. Definition 2: Post-dilatation with a non-compliant balloon ≥18 atm with nominal diameter larger than the nominal scaffold diameter but not >0.5 mm larger. 11

12. Pooled Absorb Outcomes (N=2,973)
30 days
1 year
2 years
3 years
TLF
3.4% (102)
5.8% (173)
8.2% (212)
10.8% (240)
- Cardiac death
0.2% (5)
0.4% (13)
0.7% (18)
1.7% (28)
- TV-MI
3.1% (92)
4.5% (132)
5.7% (152)
7.0% (166)
- ID-TLD
0.8% (25)
2.4% (70)
4.2% (100)
6.0% (119)
Scaffold thrombosis (def/prob)
1.2% (36)
1.9% (47)
2.7% (56)
Includes ABSORB II and ABSORB Extend 3-year data, ABSORB Japan and ABSORB China 2-year data, and ABSORB III 1-year data
Data are Kaplan-Meier estimates, % (n events) 12

13. Impact of Technique on Absorb Outcomes: Multivariable analysis Predictors of target lesion failure between 0-1 year
Technique variable
Variable absent
Variable present
Adj HR [95%CI] P
Optimal vessel sizing*
8.5%
5.2%
0.66 (0.48, 0.92)
0.01
Optimal pre-dilatation**
4.3%
6.8%
1.45 (1.07, 1.96)
0.02
Optimal post-dilatation†
5.8%
5.5%
0.91 (0.58, 1.44)
0.69
Other variables which were independently predictive of TLF between 0-1 years were female sex, diabetes, QCA %DS, mod/sev calcified lesion, and bifurcation lesion.
For a variable to be “present”, it must apply to all treated lesions. *QCA RVD ≥2.25 mm - ≤3.75 mm for all treated lesions; **Pre-dilatation performed in all lesions with a balloon to QCA RVD ratio ≥1:1; †Definition 2: Post-dilatation with a non-compliant balloon ≥18 atm with nominal diameter larger than the nominal scaffold diameter but not >0.5 mm larger. Results were directionally similar with definition 1. 13

14. Impact of Technique on Absorb Outcomes: Multivariable analysis Predictors of scaffold thrombosis between 0-1 year
Technique variable
Variable absent
Variable present
Adj HR [95%CI] P
Optimal vessel sizing*
2.6%
0.8%
0.36 (0.18, 0.72)
0.004
Optimal pre-dilatation**
0.7%
1.5%
2.25 (0.98, 5.19)
0.056
Optimal post-dilatation†
1.3%
0.78 (0.25, 2.42)
0.67
Other variables which were independently predictive of ScT between 0-1 years were diabetes, mod/sev calcified lesion, and bifurcation lesion.
For a variable to be “present”, it must apply to all treated lesions. *QCA RVD ≥2.25 mm - ≤3.75 mm for all treated lesions; **Pre-dilatation performed in all lesions with a balloon to QCA RVD ratio ≥1:1; †Definition 2: Post-dilatation with a non-compliant balloon ≥18 atm with nominal diameter larger than the nominal scaffold diameter but not >0.5 mm larger. Results were directionally similar with definition 1. 14

15. Impact of Technique on Absorb Outcomes: Multivariable analysis Predictors of target lesion failure between 1-3 years
Technique variable
Variable absent
Variable present
Adj HR [95%CI] P
Optimal vessel sizing*
4.9%
6.0%
0.90 (0.46, 1.76)
0.76
Optimal pre-dilatation**
6.7%
0.66 (0.39, 1.11)
0.12
Optimal post-dilatation†
6.2%
3.2%
0.70 (0.32, 1.57)
0.39
Other variables which were independently predictive of TLF between 0-1 years were diabetes, current/recent smoker, QCA %DS, and bifurcation lesion.
For a variable to be “present”, it must apply to all treated lesions. *QCA RVD ≥2.25 mm - ≤3.75 mm for all treated lesions; **Pre-dilatation performed in all lesions with a balloon to QCA RVD ratio ≥1:1; †Definition 2: Post-dilatation with a non-compliant balloon ≥18 atm with nominal diameter larger than the nominal scaffold diameter but not >0.5 mm larger. Results were directionally similar with definition 1. 15

16. Impact of Technique on Absorb Outcomes: Multivariable analysis Predictors of scaffold thrombosis between 1-3 years
Technique variable
Variable absent
Variable present
Adj HR [95%CI] P
Optimal vessel sizing* 0%
1.9%
6.53 (0.37, )
0.20
Optimal pre-dilatation**
2.6%
0.4%
0.23 (0.07, 0.74)
0.01
Optimal post-dilatation†
1.6%
1.3%
0.76 (0.19, 3.04)
0.70
Other variables which were independently predictive of ScT between 0-1 years were diabetes.
For a variable to be “present”, it must apply to all treated lesions. *QCA RVD ≥2.25 mm - ≤3.75 mm for all treated lesions; **Pre-dilatation performed in all lesions with a balloon to QCA RVD ratio ≥1:1; †Definition 2: Post-dilatation with a non-compliant balloon ≥18 atm with nominal diameter larger than the nominal scaffold diameter but not >0.5 mm larger. Results were directionally similar with definition 1. 16

17. Impact of Technique on Absorb Outcomes: Multivariable analysis Predictors of target lesion failure between 0-3 years
Technique variable
Variable absent
Variable present
Adj HR [95%CI] P
Optimal vessel sizing*
11.8%
10.6%
0.72 (0.53, 0.96)
0.03
Optimal pre-dilatation**
10.4%
10.7%
1.18 (0.91, 1.53)
0.22
Optimal post-dilatation†
11.1%
8.2%
0.87 (0.58, 1.30)
0.50
Other variables which were independently predictive of TLF between 0-1 years were age, diabetes, mod/sev calcified lesion, and bifurcation lesion.
For a variable to be “present”, it must apply to all treated lesions. *QCA RVD ≥2.25 mm - ≤3.75 mm for all treated lesions; **Pre-dilatation performed in all lesions with a balloon to QCA RVD ratio ≥1:1; †Definition 2: Post-dilatation with a non-compliant balloon ≥18 atm with nominal diameter larger than the nominal scaffold diameter but not >0.5 mm larger. Results were directionally similar with definition 1. 17

18. Impact of Technique on Absorb Outcomes: Multivariable analysis Predictors of scaffold thrombosis between 0-3 years
Technique variable
Variable absent
Variable present
Adj HR [95%CI] P
Optimal vessel sizing*
2.6%
2.7%
0.60 (0.32, 1.10)
0.10
Optimal pre-dilatation**
3.2%
1.9%
0.92 (0.53, 1.60)
0.77
Optimal post-dilatation†
2.9%
2.1%
0.71 (0.29, 1.74)
0.45
Other variables which were independently predictive of ScT between 0-1 years were diabetes.
For a variable to be “present”, it must apply to all treated lesions. *QCA RVD ≥2.25 mm - ≤3.75 mm for all treated lesions; **Pre-dilatation performed in all lesions with a balloon to QCA RVD ratio ≥1:1; †Definition 2: Post-dilatation with a non-compliant balloon ≥18 atm with nominal diameter larger than the nominal scaffold diameter but not >0.5 mm larger. Results were directionally similar with definition 1. 18

19. Multivariable PSP Analysis Limitations
Current follow-up is 1 year for ABSORB III, 2 years for ABSORB Japan and ABSORB China, and 3 years for ABSORB II and ABSORB Extend. Thus while the analysis is final for the 1-year results, the 1-3 year and 0-3 year analyses will not be complete until later this year.
The reasons for technique choices (e.g. low vs. high pressure post-dilatation) were not recorded, and as these decisions were not randomized we cannot rule out the impact of unmeasured confounders

20. Blinded, Pooled, Interim ABSORB IV Outcomes: Comparison to ABSORB III
ABSORB III: 2008 pts randomized 2:1 BVS:EES (1322:686)
ABSORB IV: 3000 pts being randomized 1:1 BVS:EES
ABSORB III Pooled
(N=2008)
(N=2008)1
ABSORB IV Pooled
(N=2494)2,3
QCA RVD <2.25 mm
19%
Post-dilatation (BVS)
66%
Pooled stent/scaffold thrombosis
30 days
1.0%
0.9%
1 year
1.3%
1.1%
Assuming the same event rate for each arm in ABSORB III, but with a 1:1 randomization ratio.
Based on January 16, 2016 data cut (N=2349 with 30 day FU and N=1297 with 1 year FU).
A-IV includes 25% non A-III like subjects (troponin+ NSTEMI/STEMI, 3 lesions treated, and planned staged procedures). 20

21. Blinded, Pooled, Interim ABSORB IV Outcomes: Comparison to ABSORB III
ABSORB III: 2008 pts randomized 2:1 BVS:EES (1322:686)
ABSORB IV: 3000 pts being randomized 1:1 BVS:EES
ABSORB III Pooled
(N=2008)
(N=2008)1
ABSORB IV Pooled
(N=2494)2,3
QCA RVD <2.25 mm
19% 4%
Post-dilatation (BVS)
66%
83%
Pooled stent/scaffold thrombosis
30 days
1.0%
0.9%
1 year
1.3%
1.1%
Assuming the same event rate for each arm in ABSORB III, but with a 1:1 randomization ratio.
Based on January 16, 2016 data cut (N=2349 with 30 day FU and N=1297 with 1 year FU).
A-IV includes 25% non A-III like subjects (troponin+ NSTEMI/STEMI, 3 lesions treated, and planned staged procedures). 21

22. Blinded, Pooled, Interim ABSORB IV Outcomes: Comparison to ABSORB III
ABSORB III: 2008 pts randomized 2:1 BVS:EES (1322:686)
ABSORB IV: 3000 pts being randomized 1:1 BVS:EES
ABSORB III Pooled
(N=2008)
(N=2008)1
ABSORB IV Pooled
(N=2494)2,3
QCA RVD <2.25 mm
19% 4%
Post-dilatation (BVS)
66%
83%
Pooled stent/scaffold thrombosis
30 days
1.0%
0.9%
0.3%
1 year
1.3%
1.1%
0.5%
Assuming the same event rate for each arm in ABSORB III, but with a 1:1 randomization ratio.
Based on January 16, 2016 data cut (N=2349 with 30 day FU and N=1297 with 1 year FU).
A-IV includes 25% non A-III like subjects (troponin+ NSTEMI/STEMI, 3 lesions treated, and planned staged procedures). 22

23. Impact of Technique on Absorb Outcomes: Conclusions
Data is emerging that optimizing technique when implanting the 1st generation Absorb BVS can improve mid-term outcomes
In particular, avoiding BRS implantation in very small vessels (QCA RVD <2.25 mm), and routinely performing high pressure post-dilatation with a NC balloon may reduce the rates of TLF and scaffold thrombosis
New insights regarding the impact of optimal technique on the early and late outcomes of Absorb BVS will emerge with the final 3-year data from ABSORB III, China and Japan, and when the ABSORB IV results become available 23