1. Kyoto University Hospital, Japan
THREE YEAR FOLLOW UP OF A RANDOMIZED COMPARISON OF NOBORI, BIOLIMUS A9 ELUTING STENT(BES) WITH CYPHER, SIROLIMUS ELUTING STENT(SES) FOR CORONARY REVASCULARIZATION IN JAPANESE POPULATION
Takeshi Kimura
Kyoto University Hospital, Japan
T. Muramatsu, M. Iwabuchi, S. Saito, Y. Hayashi, Y. Ikari, K. Fujii, S. Nanto, N. Inoue, A. Namiki, H. Hirayama, O. Doi, M. Kashida, J. Yajima, K. Mitsudo (P.I.)
on behalf of NOBORI JAPAN investigators

2. Potential conflicts of interest
Speaker’s name: Takeshi Kimura
 I have the following potential conflicts of interest to report:
 Consulting

3. Background
Nobori stent (Terumo Co., Tokyo Japan), is the new concept Drug Eluting Stent which has unique bioabsorbable polymer (Poly-Lactic Acid) and the anti-proliferative agent Biolimus A9. We investigated the safety and the efficacy of Nobori stent comparing to Cypher stent in Japanese population by a single blinded 3:2 randomized trial and met the primary endpoint, non inferiority in TVF. This is the first report of three year clinical follow up data of Nobori Biolimus Eluting stent compared to Cypher Sirolimus Eluting stent in Japanese population.

4. NOBORI Japan Trial Design
3:2 randomization, single blind - up to two vessels
Up to two de novo lesions in different epicardial vessels
Vessel diameter: mm, Lesion length: ≤ 30 mm
Pre-dilatation required
PIs: Dr Kazuaki Mitsudo
　 Dr Hidehiko Honda　　
N = 335 patients (15 sites: Japan)
Nobori BES
(n= 200)
Cypher SES
(n= 135)
Primary endpoint （TVFΔ 9%）
Clinical / TVF
30d
3mo
6mo
8mo
9mo
1yr
2yr
3yr
4yr
5yr
Angio
QCA
Primary endpoint:
Target Vessel Failure (Cardiac death, MI, TVR) at 9months
Secondary endpoints:
Acute gain after PCI / Late loss / Restenosis rate / %DS at 8 months
MACE (Cardiac Death, MI, TLR) / TLR / TVR / TVF / Stent thrombosis at
9 months & 1, 2, 3, 4, 5Y

5. Baseline Demographics
(%)
Nobori
n=194
Cypher
n=132 p
Age (years SD)
67.1±10.3
67.7±9.3
0.59
Male
71.6
72.0
0.95
Prior MI
20.6
21.2
0.90
Unstable angina
16.5
11.4
0.20
Diabetes
38.7
39.4
0.89
Insulin dependent
8.8
6.8
0.68
Hypertension
76.8
84.1
0.11
Hyperlipidemia
77.3
81.8
0.33
Smoking （past 6mo）
25.8
18.2

6. Lesion Location, Classification
Nobori
n=194
Cypher
n=132 p
Lesion (%)
LAD
39.9
44.7
0.64
LCX
27.1
24.0
RCA
33.0
31.3
ACC-AHA (%) A
9.2
11.3
0.32 B1
21.1
26.7 B2
59.2
49.3 C
10.6
12.7

7. Procedural Characteristics
Nobori
n=194
Cypher
n=132 p
nº of lesions
218
150 -
nº of lesions per patient
1.13
1.14
0.69
nº of stents
234
163
1 stent (%)
92.7
91.3
0.64
2 stents (%)
7.3
8.7
nº of stents per patient
1.22
1.24
0.66
RVD (mm±SD)
2.68±0.57
2.68±0.54
0.99
Lesion length (mm±SD)
12.64±5.52
12.82±6.81
0.77
Stent diameter (mm±SD)
3.0±0.38
3.0±0.37
0.95
Stent length (mm±SD)
21.0±6.7
21.0±7.8
Overlap (%)
Max. inflation pressure (atm±SD)
12.8±2.5
14.8±1.9
<0.0001

8. Primary Endpoint TVF at 9 months
Nobori (BES) was NOT Inferior to Cypher (SES)
(P<0.001 for non-inferiority)
(%)
(Follow-up rate at 9months = 98.8%)
Nobori
Cypher

9. Secondary Endpoint Late Loss, Binary Restenosis at 8months
(mm)
p=0.54
p=0.67
p=0.74
Nobori (n=184)
Cypher (n=122)

10. TVF up to 3 years (TVF: Cardiac death, MI, TVR)
n of pts at Risk
Nobori
Cypher

11. MACE up to 3 years (MACE : Cardiac death, MI, TLR)
Follow-up rate at 3years = 86.0%
n of pts at Risk
Nobori
Cypher

12. Cardiac Death up to 3 years
n of pts at Risk
Nobori
Cypher

13. TLR up to 3 years
n of pts at Risk
Nobori
Cypher

14. TVR up to 3 years
n of pts at Risk
Nobori
Cypher

15. MI up to 3 years
n of pts at Risk
Nobori
Cypher

16. Subgroup Analysis for TVF：Primary Endpoint
number
Subgroups
Nobori
Cypher
Nobori Better
Cypher Better
p value
HR % CI
Age =< 65 77 49
0.48
0.64
( )
Age > 65
113 79
0.65
1.24
( )
without DM
116
0.94
1.04
( )
with DM 74 51
0.92
( )
LAD: no
105 61
0.89
1.08
( )
LAD : yes 85 67
0.90
( )
Men 54 36
( )
Women
136 92
0.97
1.02
( )
Single vessel
166
112
0.79
( )
Double vessel 24 16
0.68
1.44
( )
One stent per patient :no 37 25
0.95
0.96
( )
One stent per patient: yes
153
103
1.00
( )
Previous MI: no
151
102
0.99
1.01
( )
Previous MI: yes 39 26
( )
Ref Seg under 2.5mm: no 97 76
0.82
1.14
( )
Ref Seg under 2.5mm: yes 93 52
( )

17. Stent thrombosis up to 3 years
No definite or probable Stent Thrombosis according to ARC definition in both groups
Patients on Dual Anti-Platelet Therapy
1 year
2 years
3 years
Nobori
85%
78%
74％
Cypher
87%
80%
76％
The cases in whom CRF was collected were analyzed.
ASA and Cilostazol were administered in 2 patients (1.2%) in the Nobori group, and in 2 patients (1.7%) in the Cypher group, respectively.

18. Conclusion
In this first randomized clinical trial of Nobori and Cypher stent in Japanese population, Nobori stent was found non-inferior to Cypher in TVF, the primary endpoint.
TLR free rate at 3 years of Nobori tended to be higher than that of Cypher.
MACE and TVF free rate of both stents at three years were comparable.
Further long term follow-up up to 5 years is planned to evaluate longer term safety of Nobori Stent.