1. Bioabsorbable Stent: Unsolved Issues & Cahallenges in Japan
Takashi Akasaka, MD, PhD, FESC
Department of Cardiovascular Medicine
Wakayama Medical University, Japan

2. Disclosure Statement of Financial Interest
Takashi Akasaka, MD, PhD
Within the past 12 months, I or my spouse/partner have had a financial interest/arrangement or affiliation with the organization(s) listed below.
Grant/Research Support : Abbott Vascular Japan
Boston Scientific Japan
Goodman Inc.
St. Jude Medical Japan
Terumo　Inc.
Consulting Fees/Honoraria : Daiichi-Sankyo Pharmaceutical Inc.

4. Backgrounds
Theoretically, bioresorbable vascular scaffolds (BVS) may
overcome the shortcomings of permanent metallic prosthesis.
However, whether BVS are as safe and effective as metallic DES
prior to complete bioresorption is currently unknown.
Aim
Therefore, a randomized, controlled trial comparing the clinical and
angiographic outcomes of BVS with those of Xience
cobalt-chromium everolimus-eluting stents (CoCr-EES) was designed
to support regulatory approval of the Absorb BVS in Japan.

5. ABSORB Japan Randomized 2:1 BVS
Prospective, randomized, active control, single-blind, non-inferiority, multi-center Japanese study
Inclusion: Patients with up to 2 de novo target lesions in separate native coronary arteries
Lesion length ≤ 24 mm, Dmax ≥ 2.5 mm to ≤ 3.75 mm, %DS ≥50% to <100%
Exclusion: AMI, EF <30%, eGFR <30 mL/min/1.73m2,
LMCA, Ostial lesion, Excessive vessel tortuosity, Heavy calcification,
Myocardial bridge, Bifurcation with side branch ≥2 mm
Randomized 2:1
BVS
Tx. with single study device Diameter: 2.5, mm
Length: 8, 12, 18, 28 mm
CoCr-EES Tx. with single study device Diameter: 2.5, mm
Length: 8, 12, 18, 28 mm
Primary Clinical Endpoint: Target Lesion Failure (TLF): Cardiac death, TV-MI, Ischemia Driven-TLR at 12 months
Major Secondary Angiographic Endpoint: In-segment Late Lumen Loss at 13 months

6. Sample Size Calculation & 12-Month TLF (ABSORB Japan)
Randomization ratio: 2 to 1
Non-inferiority study design
Significance level: 5% (one tail)
Assumed event rate of 12-month TLF in the CoCr-EES arm: 9%
Non-inferiority Margin: 8.6%
Power: 90%
Required Sample Size: 390 patients (BVS:260, CoCr-EES:130)
Total Sample Size: 400 patients assuming dropouts
If the non-inferiority P-value from the one-sided Farrington-Manning test is <0.05, BVS is regarded as non-inferior to CoCr-EES for the primary endpoint.
True rate was based on results from SPIRIT III RCT and SPIRIT III Japan, and 95% UCI was applied.
Non-inferiority margin was ½ of treatment effect of CoCr-EES over BMS,
i.e. (1st Gen DES – BMS) + (CoCr-EES – 1st Gen DES)

7. Investigational Sites (38)
Shin-Tokyo Hospital, Chiba
Saitama Sekishinkai Hospital, Saitama
Saiseikai Yokohamashi Tobu Hospital, Kanagawa
Shonan Kamakura General Hospital, Kanagawa
The Cardiovascular Institute, Tokyo
Tokyo Women's Medical University Hospital, Tokyo
Kurashiki Central Hospital, Okayama
Kansai Rosai Hospital, Hyogo
Shinkoga Hospital, Fukuoka
Iwate Medical University Hospital, Iwate
Sakakibara Heart Institute, Tokyo
Kyoto University Hospital, Kyoto
Saiseikai Kumamoto Hospital, Kumamoto
Osaka University Hospital, Osaka
Tokushima Red Cross Hospital, Tokushima
Miyazaki Medical Association Hospital, Miyazaki
Teikyo University Hospital, Tokyo
Fujita Health University Hospital, Aichi
Kanto Rosai Hospital, Kanagawa
National Cerebral and Cardiovascular Center, Osaka
Kurume University Hospital, Fukuoka
Kokura Memorial Hospital, Fukuoka
Hokkaido Social Insurance Hospital, Hokkaido
Showa University Hospital, Tokyo
Sakurabashi Watanabe Hospital, Osaka
Yamaguchi University Hospital, Yamaguchi
Mitsui Memorial Hospital, Tokyo
The University of Tokyo Hospital, Tokyo
Tokai University Hospital, Kanagawa
Japanese Red Cross Nagoya Daini Hospital, Aichi
Tenri Hospital, Nara
Toho University Ohashi Medical Center, Tokyo
Kobe University Hospital, Hyogo
Saitama Medical Center Jichi Medical University, Saitama
Dokkyo Medical University Hospital, Tochigi
Juntendo University Hospital, Tokyo
Wakayama Medical University Hospital, Wakayama
Tsukuba Medical Center Hospital, Ibaraki

8. ABSORB Japan Study Organization
Study Protocol Committee:
Takeshi Kimura (Principal Investigator), Ken Kozuma, and Kengo Tanabe
Data management:
Abbott Vascular
Safety Oversight Committee:
Harvard Clinical Research Institute (HCRI)
Clinical Events Committee:
Angiographic Core laboratory:
Beth Israel Deaconess Medical Center, Inc., Angiographic Core Lab,
IVUS Core laboratory:
Cardiovascular Core Analysis Laboratory (CCAL), Stanford University
OCT Core laboratory:
Cardialysis BV, Rotterdam, the Netherlands
MSCT Core laboratory:
Cardiocore Japan

9. Patient Flow Chart EES (N=1618) BES (N=1617) BVS (N=266) BES (N=1601)
Randomized
(N=400)
Enrollment from 38 Japanese centers
Between April 27, 2013 and December 27, 2013
BVS (N=266)
CoCr-EES (N=134)
Withdraw consent without POCE: 1
Withdraw consent without POCE: 1
EES (N=1618)
BES
(N=1617)
Intention-to-treat Population (N=398)
BVS (N=265)
CoCr-EES (N=133)
BVS (N=266)
BES (N=263)
12-Month Clinical FU Complete (N=397: 99.7%) )
BES
(N=1601)
BVS (N=264)
CoCr-EES (N=133)
13-Month Angiographic FU Qualified (N=378: 95.0%)
BVS (N=252)
CoCr-EES (N=126)

10. Baseline Patient Characteristics
BVS
(266 Patients)
CoCr-EES
(134 Patients)
P-value
Age (years)
67.1 ± 9.4
67.3 ± 9.6
0.90
Male
79%
74%
0.25
BMI (kg/m2)
24.0 ± 3.0
24.3 ± 3.0
0.41
Current Tobacco Use
20%
22%
0.69
Stable CAD
90%
84%
0.054
Diabetes
36%
0.96
Prior PCI/CABG
38%
0.70
Prior MI
16%
24%
0.06
eGFR <60 (mL/min)
32%
28%
0.37

11. Lesion Location and Morphology
BVS
(275 Lesions)
CoCr-EES
(137 Lesions)
P-Value
LAD
46%
42%
0.46
LCX/Ramus
23%
26%
0.45
RCA
31%
0.92
Calcification (Mod./Severe)
28%
33%
0.28
Tortuosity (Mod./Severe)
8.4%
8.0%
0.90
Eccentric
82%
83%
0.84
Bifurcation
37%
0.32
Type A
4.0%
3.6%
0.86
Type B1
20%
Type B2
56%
50%
0.22
Type C
0.15

12. Baseline QCA BVS (275 Lesions) CoCr-EES (137 Lesions) P-value
Lesion Length (mm)
13.4 ± 5.3
13.3 ± 5.5
0.87
Pre RVD (mm)
2.71 ± 0.45
2.79 ± 0.46
0.10
Pre MLD (mm)
0.96 ± 0.33
0.99 ± 0.36
0.40
Pre %DS (%)
64.5 ± 11.1
64.7 ± 10.9
0.91

13. Procedural Information
BVS
(266 Patients)
(275 Lesions)
CoCr-EES
(134 Patients)
(137 Lesions)
P-value
Single Target Lesion
97%
98%
0.76
Non-study Lesion Treated
7.5%
1.00
% Pre-Dilatation
100%
% Post Dilatation
82%
77%
0.25
Bailout Procedure
1.8% (5/275)
0.7% (1/137)
0.67
- By BVS 4
0.31
- By CoCr-EES 1
Total Device Length (mm)
20.2 ± 5.8
19.5 ± 5.8
0.22

14. Acute Success and Procedure Duration
Device Success Procedure Success Procedure Duration
P=1.00
P=0.72
P=0.04
49.8±24.8 min
44.9±21.7 min
BVS CoCr-EES BVS CoCr-EES
BVS CoCr-EES
Device success: Successful deployment of the assigned device at the target lesion
　　　　with <30% residual stenosis
Procedure success: Device success without TLF during the hospital stay (max. of 7 days)

15. Balloon Diameters and Inflation Pressure
Nominal Nominal Expected Nominal Expected Expected
Pre-dilatation
11.6 ± 3.8 atm.
11.9 ± 3.7 atm.
P=0.52
Deployment
10.4 ± 3.0 atm.
11.2 ± 2.7 atm.
P=0.003
Post-dilatation
15.5 ± 4.2 atm.
16.0 ± 3.9 atm.
P=0.24
Final Balloon
14.7 ± 4.1 atm.
15.1 ± 4.1 atm.
P=0.36
Inflation
Pressure
Pre-dilatation
Deployment
Post-dilatation
Final
Expected diameter was calculated based on the compliance chart of the device

16. Post Procedural QCA BVS (275 Lesions) CoCr-EES (137 Lesions) P-value
RVD Post (mm)
2.75 ± 0.42
2.85 ± 0.43
0.03
In-Device MLD Post (mm)
2.43 ± 0.37
2.64 ± 0.40
<0.0001
In-Device %DS Post (%)
11.6 ± 7.5
7.3 ± 8.1
In-Segment MLD Post (mm)
2.20 ± 0.39
2.27 ± 0.43
0.15
In-Segment %DS Post (%)
20.0 ± 6.7
20.6 ± 8.80
0.49
In-Device Acute Gain (mm)
1.47 ± 0.40
1.65 ± 0.40
In-Segment Acute Gain (%)
1.25 ± 0.41
1.28 ± 0.45

17. Primary Endpoint: 12-Month TLF (through 393 days)
Difference and Upper 95% Confidence Limit
NI Margin = 8.6%
P=0.85
Non-inferiority P <
0.39% ●
3.95%
The one-sided upper 95% confidence limit for the 0.39% observed difference in event rates was 3.95%, suggesting that any absolute difference between the 2 devices is likely to be small.
Likelihood score method by Farrington and Manning

18. Primary Endpoint: 12-Month TLF (through 393 days)
BVS at Risk
266
259
256
251
CoCr-EES at Risk
134
131
130
128

19. 12-Month Clinical Outcomes (~393-Day )
BVS
(N=266)
CoCr-EES
(N=134)
P-value
TLF (CD/TV-MI/ID-TLR)
4.2% (11/265)
3.8% (5/133)
0.85
- Cardiac Death
0.0% (0/265)
0.0% (0/133)
1.00
- Target Vessel MI
3.4% (9/265)
2.3% (3/133)
0.76
- Ischemia driven-TLR
2.6% (7/265)

20. 12-Month Definite/Probable ST
0 days
37 days
208 days
393 days
BVS at Risk
266
262
260
257
CoCr-EES at Risk
134
132
131

21. Characteristics of ST Cases
The 6 ST cases appear to be at high risk for ST
(BVS: 1.5% / 4 cases, CoCr-EES: 1.5% / 2 cases)
Small residual in-segment MLD post-procedure (4 BVS, 2 CoCr-EES)
DAPT discontinuation (1 BVS, 1 CoCr-EES)
Diabetes (2 BVS, 1 CoCr-EES)
No post-dilatation or underexpansion (2 BVS, 0 CoCr-EES)

22. Major Secondary Angiographic Endpoint: 13-Month In-Segment LLL
Upper 95% Confidence Limit of the Difference
NI Margin = mm
P=0.74
Non-inferiority P <
0.13 mm
0.01 mm
0.12 mm ●
0.07 mm
Asymptotic test statistic based on Z test

23. Cumulative Distribution Function Curves for In-segment MLD
Pre
0.96±0.33 mm
0.99±0.36 mm
P=0.42
Follow-up
2.08±0.45 mm
2.15±0.50 mm
P=0.18
Post
2.21±0.39 mm
2.26±0.43 mm
P=0.19

24. Impact of Post-procedure Intracoronary Imaging
In-device MLD
BVS
CoCr-EES
P=0.16
P=0.44
P=0.90
P=0.72
No complications were noted by the post-procedure intracoronary imaging after BVS implantation.
However, in both BVS and EES groups, post-procedure intracoronary imaging did not affect
the in-device MLD at post-procedure and at 13-month follow-up.

25. Study Limitations
Large non-inferiority margin for the primary clinical endpoint, particularly with event rate lower than anticipated
ABSORB Japan was designed to support regulatory approval of the Absorb BVS in Japan. The Japanese Regulatory Agency requested a clinical primary endpoint and agreed to a relatively large non-inferiority margin to keep the study sample size reasonable.
Although TLF rates of both BVS and CoCr-EES were lower than the anticipated rate of 9%, the 0.39% observed difference (P=0.85) suggest that the 2 devices are similar.
Underpowered to evaluate the low frequency events such as ST
Inclusion of a highly selected patient population
The study provides data for a patient population typical of pivotal studies for approval.
Data in broader patient populations will be studied in subsequent trials.

27. ABSORB III 1-Year TLF Components

28. 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

29. 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 11 2 71 30 9 3
# Risk:
241
133
238
1067
542
1058
540
Median based on pooled Absorb and Xience

30. 1-year ST in Very Small Vessels Impact of Post-Dilatation & pressure
Absorb
　11
238 6 74 5
164 2
105
Xience
133 79 54 36

31. ABSORB Japan Imaging Follow-up
Clinical FU
Imaging FU
The ABSORB Japan had an extensive imaging follow-up protocol
including angiography, IVUS, OCT, and MSCT.
Post-procedure intracoronary imaging evaluation was mandatory
in the IVUS and OCT-1 groups, while it was not allowed
in the OCT-2 group.

32. Assessment of BVS by OCT
Ormiston J A et al. Circ Cardiovasc Interv 2012;5:

33. Lesion preparation before BVS implantation by OCT
Pre-dilatation
Lesion
Preparation

34. Conclusions In the ABSORB Japan trial, BVS demonstrated a similar
mid-term (12-month) clinical safety and efficacy profile as
CoCr-EES, with comparable 13-month angiographic outcomes.
A risk of scaffold thrombosis has been reported in BVS, especially in cases with small RVD, lesion preparation before BVS implantation and post dilation with high pressure may allow us to reduce scaffold thrombosis.
Further coronary imaging studies using OCT, etc., may demonstrate the mechanism of scaffold thrombosis in BVS
in detail in the near future.

36. Frequencies of atherosclerotic findings in BMS
p = 1.000
p = 0.016
p = 0.135
p = 0.031
p = 0.046
Frequency (%)
(Kitabata H, et al. Am Heart J 2012;163: )

37. Incidence of symptomatic coronary events associated with the stented segment
(Kitabata H, et al. Am Heart J 2012;163: )