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

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

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.

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: 2.5-3.5 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

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

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

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

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

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

TVF up to 3 years (TVF: Cardiac death, MI, TVR) n of pts at Risk 0 365 730 1095 Nobori 190 156 153 146 Cypher 129 111 110 103

MACE up to 3 years (MACE : Cardiac death, MI, TLR) Follow-up rate at 3years = 86.0% n of pts at Risk 0 365 730 1095 Nobori 190 158 155 148 Cypher 129 111 110 104

Cardiac Death up to 3 years n of pts at Risk 0 365 730 1095 Nobori 192 167 165 159 Cypher 130 118 117 111

TLR up to 3 years n of pts at Risk 0 365 730 1095 Nobori 192 166 163 157 Cypher 130 114 113 107

TVR up to 3 years n of pts at Risk 0 365 730 1095 Nobori 192 164 161 155 Cypher 130 114 113 106

MI up to 3 years n of pts at Risk 0 365 730 1095 Nobori 190 159 157 151 Cypher 129 115 114 108

Subgroup Analysis for TVF：Primary Endpoint number Subgroups Nobori Cypher Nobori Better Cypher Better p value HR 95% CI Age =< 65 77 49 0.48 0.64 (0.19-2.21) Age > 65 113 79 0.65 1.24 (0.49-3.15) without DM 116 0.94 1.04 (0.37-2.93) with DM 74 51 0.92 (0.33-2.72) LAD: no 105 61 0.89 1.08 (0.36-3.21) LAD : yes 85 67 0.90 (0.34-2.59) Men 54 36 (0.20-4.01) Women 136 92 0.97 1.02 (0.43-2.38) Single vessel 166 112 0.79 (0.39-2.04) Double vessel 24 16 0.68 1.44 (0.26-7.85) One stent per patient :no 37 25 0.95 0.96 (0.31-3.04) One stent per patient: yes 153 103 1.00 (0.38-2.62) Previous MI: no 151 102 0.99 1.01 (0.43-2.36) Previous MI: yes 39 26 (0.20-4.02) Ref Seg under 2.5mm: no 97 76 0.82 1.14 (0.36-3.60) Ref Seg under 2.5mm: yes 93 52 (0.30-2.09)

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.

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.