P LEASANT ECO- Comparison of Efficacy between ‘COroflex PLEASe’ ANd ‘Taxus-Liberte’ stent Hyo-Soo Kim MD, PhD on behalf of the investigators Seoul National University Hospital (SNUH), Seoul, Korea

Disclosure Statement of Financial Interest Within the past 12 months, I or my spouse/partner have had a financial interest/arrangement or affiliation with the organization(s) listed below. Affiliation/Financial Relationship Company Grant/Research Support Consulting Fees/Honoraria Abbott Vascular, Boston Scientific, Medtronic, B Braun Astra Zenica, Daichi Sankyo, Eli Lily, Sanofi Aventis

Background Various type of paclitaxel-eluting stents available in the market All PES infer efficacy and safety from the TAXUS series of trials (data transferability issue) No head-to-head comparison between different types of PES Drug Paclitaxel Drug Dose 1µm/mm2 Drug Release In between Taxus-SR and -MR Polymer coating Polysulfone® : non-absorbable, thermostable Translute : biostable Coating thickness 4µm 18µm Strut thickness 120µm 97µm Manufacturer Coroflex PleaseTM Stent Taxus LiberteTM Stent

Objectives Hypothesis To evaluate the clinical efficacy, angiographic outcome and safety of the CoroflexTM-Please stent compared with the TaxusTM-Liberte stent Hypothesis CoroflexTM-Please is non-inferior to TaxusTM-Liberte in clinical efficacy, angiographic outcome and safety at 9 months

General Exclusion Criteria Angiographic Exclusion Criteria Patient Eligibility Inclusion Criteria > 50% stenosis by visual estimation with evidence of myocardial ischemia or > 70% stenosis Evidence of myocardial ischemia Stable angina Unstable angina Recent infarction, silent ischemia + functional study or reversible changes in the ECG c/w ischemia Target lesion must be located in a native coronary artery 2. 5mm ≤ RVD ≤ 4.0mm General Exclusion Criteria GI or GU bleeding ≤3 months, major surgery ≤ 2 months Elective surgical procedure planned ≤ 9 months Life expectancy < 1 year LVEF < 25%, or in shock STEMI who require primary PCI STEMI ≤ 48 hours Creatinine level ≥ 3.0mg/dL or dependence on dialysis Severe hepatic dysfunction (AST, ALT ≥ x3 UNL) Patients who have received any stent implantation in the target vessel prior to enrollment Angiographic Exclusion Criteria Significant LM stenosis requiring revascularization BMS or DES ISR True bifurcation lesions requiring two stents

Trial Design Prospective, open label, two-arm, randomized multi-center trial 915 Patients Matching Enrollment Criteria 18 centers in Korea CoroflexTM-Please N=610 Randomization 2:1 TaxusTM-Liberte N=305 Percutaneous Coronary Intervention 1mo 3mo 9mo 12mo Clinical Angiographic 3yr 2yr 4yr 5yr Primary Endpoint: TVR Secondary endpoint evaluation JaeBin Seo,,,, HS Kim. Trials 2009, 10:98

Study Endpoints Primary Endpoint: : Clinically driven Target Vessel Revascularization (TVR) at 9 months (for comparison of stenting with CoroflexTM-Please vs. TaxusTM-Liberte) Secondary Endpoints: Clinical safety and efficacy end points 1) Major Cardiac Adverse Events (MACE) ; all death, cardiac death, Myocardial infarction (Q-wave and non-Q wave), TVR 2) Target Vessel Failure (TVF) ; cardiovascular death, myocardial infarction, clinically driven TVR 3) Stent thrombosis Angiographic efficacy end points 1) In-stent binary restenosis by QCA In-stent and in-lesion late loss by QCA In-stent and in-lesion MLD and percentage diameter stenosis by QCA immediately after the index procedure and at 9 months of follow-up

Statistical Assumption Primary Endpoint : Clinically driven Target vessel Revascularization (TVR) at 9 Months TVR of TaxusTM-Liberte: 8% (assumed) Noninferiority margin: + 5% Sampling ratio: CoroflexTM-Please : TaxusTM-Liberte = 2:1 (type I error: 0.05; statistical power: 80%; attrition: 10%)  915 patients needed (610 Coroflex PleaseTM + 305 Taxus LiberteTM) Secondary Endpoint : Late Luminal Loss (LLL) at 9 Months LLL of Taxus LiberteTM: 0.400±0.500 mm (assumed) Noninferiority margin: + 0.150 mm Sampling ratio: CoroflexTM-Please : TaxusTM-Liberte = 2:1 (type I error: 0.05; statistical power: 80%; attrition: 30%)  450 patients needed (300 Coroflex PleaseTM + 150 Taxus LiberteTM)

Participating Centers 18 Hospitals in Republic of Korea Seoul National University Hospital Seoul National University Bundang Hospital KyungHee University Medical Center Inha University Hospital Inje University Sanggye Paik Hospital Soonchunhyang Univeristy Hospital Chung-Ang University Medical Center Keimyung University Dongsan Hospital Yeungnam University Medical Center Inje University Pusan Paik Hospital Kosin University Gospel Hospital Ulsan University Hospital The Catholic University of Korea, Uijeonbu St. Mary’s Hospital The Catholic University of Korea, St. Vincent’s Hospital Boramae Medical Center Eulgi General Hospital Konyang University Hospital Sejong General Hospital

Study Flow CoroflexTM-Please N=631 Randomization TaxusTM-Liberte N=314 Enrolled and randomized (N= 955 Patients) CoroflexTM-Please N=631 Randomization 2:1 TaxusTM-Liberte N=314 Did not receive allocated stent: 25 - DES: 21 - BMS: 0 - CABG: 2 - POBA: 1 - Not inserted: 1 Failed PCI: 1 Did not receive allocated stent : 11 - DES: 11 - BMS: 0 - CABG: 0 - POBA: 0 - Not inserted: 0 Failed PCI: 1 Received Coroflex (605 patients, 777 lesions) Received Taxus (302 patients, 392 lesions) 955 (631+314) Patients Analyzed According to ITT

Baseline Characteristics Variables ― no. (%) Coroflex (N=631) Taxus (N=314) p-value Age, years ― mean±SD 62.4±10.0 63.6±9.8 0.074 Males 398 (63.1) 201 (64.0) 0.778 Body-mass index, kg/m2 25.0±3.2 25.0±3.1 0.776 Diabetes mellitus 246 (39.0) 121 (38.5) 0.893 Chronic renal failure 10 (1.6) 1 (0.3) 0.087 Hypertension 403 (63.9) 198 (63.1) 0.808 Hypercholesterolemia 293 (46.4) 146 (46.5) 0.986 Smoking status 0.904 Never smoker 328 (52.0) 162 (51.6) Ex-smoker 118 (18.7) 56 (17.8) Current smoker 185 (29.3) 96 (30.6) Previous history of myocardial infarction 31 (4.9) 8 (2.5) 0.085 History of CABG 2 (0.6) 0.220 History of PCI 63 (10.0) 25 (8.0) 0.314 History of cerebrovascular disease 45 (7.1) 17 (5.4) 0.315 Table 1

Baseline Characteristics Variables ― no. (%) Coroflex (N=631) Taxus (N=314) p-value Multivessel disease 345 (54.7) 168 (53.5) 0.733 Left ventricular ejection fraction, % 61.1±9.7 61.1±9.6 0.991 Clinical indication 0.325 Stable angina 305 (48.3) 143 (45.5) Unstable angina 209 (33.1) 109 (34.7) NSTEMI 97 (15.4) 57 (18.2) STEMI 20 (3.2) 5 (1.6) Medications at discharge Aspirin 624 (98.9) 313 (99.7) 0.211 Clopidogrel 623 (98.7) 311 (99.0) 0.673 Statin 490 (77.7) 262 (83.4) 0.038 ACE inhibitor 197 (31.2) 115 (36.6) 0.096 Angiotensin II-receptor antagonist 194 (30.7) 88 (28.0) 0.389 Beta-blocker 415 (65.8) 212 (67.5) 0.592 Calcium-channel blocker 147 (23.3) 76 (24.2) 0.757 Table 1

Lesion and Procedural Characteristics Variables ― no. (%) Coroflex (N=828) Taxus (N=417) p-value* Lesion Location: Left anterior descending 395 (47.7) 211 (50.6) 0.749 Left circumflex 186 (22.5) 89 (21.3) Right coronary 238 (28.7) 114 (27.3) Left main 9 (1.1) 3 (0.7) ACC-AHA B2/C type 360 (43.6) 192 (46.4) 0.366 Total occlusion 69 (8.4) 35 (8.5) 0.956 Thrombus-containing 65 (7.9) 27 (6.5) 0.398 Bifurcation lesions 79 (9.6) 44 (10.6) 0.573 Calcification 351 (42.5) 180 (43.5) 0.768 Minimal luminal diameter, mm 0.78±0.48 0.76±0.49 0.612 Reference vessel diameter, mm 2.83±0.51 2.80±0.49 0.307 Diameter stenosis, % 72.5±16.0 72.8±15.6 0.668 Lesion length, mm 18.8±10.8 20.1±11.2 0.070 Lesion length > 20mm 263 (35.8) 154 (41.5) 0.074 No. of stents per lesion 1.14±0.38 1.11±0.32 0.062 No. of stents per patient** 1.48±0.81 1.47±0.78 0.782 Total stent length per lesion ― mm 26.1±12.5 26.4±11.6 0.686 Total stent length per patient** 34.7±22.2 35.0±21.9 0.408 Use of intravascular ultrasound (IVUS)* 316 (50.1) 160 (51.0) 0.800 Table 2 *comparisons were performed using the generalized estimating equations (GEE), and **with the independent t-test

Clnically Driven Target Vessel Revascularization 1˚ Endpoint Clnically Driven Target Vessel Revascularization 30 HR: 2.43 (1.50-3.94) Non-Inferiority p-value=1.000 Inferiority p-value<0.001 20 Cumulative incidence rate (%) Coroflex: 14.6% 10 Taxus: 6.4% 3 6 9 Months after initial procedure Patient Number at Risks Coroflex 631 604 574 546 Taxus 314 304 300 292

Clinical Outcomes at 9 Months 2˚ Endpoint Clinical Outcomes at 9 Months Myocardial Infarction p=0.012 Stent thrombosis (definite+probable) p=0.317 All-Cause Death p=0.574 Cardiac Death p=0.866 Table 5: ITT Coroflex N=631 Taxus N=314 Coroflex N=631 Taxus N=314 Coroflex N=631 Taxus N=314 Coroflex N=631 Taxus N=314

Clinical Outcomes at 9 Months 2˚ Endpoint Clinical Outcomes at 9 Months CD-TLR(%) p<0.001 CD-TVR (%) p<0.001 Table 5: ITT Coroflex N=631 Taxus N=314 Coroflex N=631 Taxus N=314

Composite Endpoints 2˚ Endpoint Death or MI p=0.044 TLF (C-death, MI, TLR) p<0.001 TVF (C-death, MI, TVR) p<0.001 MACE (A-death, MI, TVR) p<0.001 19.0 17.6 17.9 Table 5: ITT Coroflex N=631 Taxus N=314 Coroflex N=631 Taxus N=314 Coroflex N=631 Taxus N=314 Coroflex N=631 Taxus N=314

ARC Stent Thrombosis 2˚ Endpoint Definite ST (%) p=0.076 Definite/Probable ST p=0.317 Table 5: ITT Coroflex N=631 Taxus N=314 Coroflex N=631 Taxus N=314

Subgroup Analysis for TVR Subgroups Pt No. Relative Risk of TVR (95% CI) Int P DM Yes (N=349) 0.771 No (N=596) Diffuse long lesion ≥ 28mm (N=261) 0.838 < 28mm (N=684) Age ≥ 65 (N=439) 0.935 < 65 (N=506) Sex Male (N=599) 0.869 Female (N=346) Multivessel ds (N=513) 0.739 (N=432) ACS (N=497) 0.253 (N=448) Overall 0.5 1 2 4 8 16 Favors Taxus

QCA Data 2˚ Endpoint Variables ― no. (%) Coroflex (N=834) Taxus p-value* Before procedure Lesion length ― mm 18.8±10.8 20.1±11.2 0.070 Reference vessel diameter ― mm 2.83±0.51 2.80±0.49 0.307 Minimal luminal diameter― mm 0.78±0.48 0.76±0.48 0.518 Diameter stenosis ― % 72.5±16.0 73.0±15.2 0.544 Immediately after procedure Minimal luminal diameter ― mm 2.54±0.45 2.50±0.44 0.174 8.88±8.71 9.68±8.74 0.145 Acute gain ― mm 1.76±0.53 1.74±0.53 0.463 Follow-up at 9 months 1.82±0.77 1.97±0.65 0.004 35.15±24.50 28.52±19.51 <0.001 Late luminal loss ― mm 0.71±0.64 0.52±0.50 Binary restenosis ― % 117 (14.1) 40 (9.6) 0.034 Table 3-1 *comparisons were performed using the generalized estimating equations (GEE).

Predefined non-inferiority margin: 0.150 mm In-Stent Late Luminal Loss CoroflexTM (N=550) 0.710±0.64 mm TaxusTM (N=286) 0.520±0.50 mm Mean ΔLL: 0.197 mm Upper 95% CI: 0.275 mm Lower 95% CI: 0.119 mm Inferiority p-value <0.001 Predefined non-inferiority margin: 0.150 mm Table 4: PP, all lesions Inferior! 0.00 0.02 0.04 0.06 0.08 0.10 0.12 0.14 0.16 0.18 0.20 0.22 0.24 0.26 0.28 0.30 mm 2-sided 95% CI

Late Luminal Loss In-stent In-segment Coroflex Taxus Coroflex Taxus 0.710±0.64 vs. 0.520±0.50 (p<0.001) 0.480±0.61 vs. 0.330±0.50 (p<0.001) 100 100 -1.0 0.0 1.0 2.0 3.0 -1.0 0.0 1.0 2.0 3.0 80 80 60 60 % of Lesions 40 40 Coroflex Taxus Coroflex Taxus 20 20 Late Luminal Loss (mm)

P Summary of LEASANT ECO- The efficacy of Coroflex Please was inferior to Taxus Liberte with regard to clinically driven TVR and MI up to 9 months The CoroflexTM-Please stent showed significantly higher in-stent LL compared to TaxusTM-Liberte at 9-month angiographic F/U. The incidence of cardiac death and ST did not differ significantly between CoroflexTM-Please and TaxusTM-Liberte, although numerically higher in the CoroflexTM-Please group. Not all PES were borne the same. Head-to-head trials are needed to confirm efficacy and safety of newly developed stents before automatically assuming data transferability.

Thank You For Your Attention

Difference in Stent Designs TaxusTM-Liberte : designed to enable even drug distribution CoroflexTM-Please : large open cell area (for bifurcation stenting)

CoroflexTM-Please PECOPS I trial PECOPS II trial (Clin Res Cardiol, 2007) 1-Year Clinical Outcome (N=97) MACE: 13.5% TVR: 9.4% ST: 2.1% PECOPS II trial (J Interv Cardiol. 2010) 1-Year Clinical Outcomes (N=131) MACE: 15.5% TVR: 14.5% ST: 0.8% 6-Month Angiography (N=129) LLL, in-stent: 0.27±0.59 mm LLL, in-segment: 0.21±0.70 mm %DS: 26.4±19.9%

TaxusTM-Liberte TAXUS-ATLAS (JACC, 2007) COMPARE (JACC, 2011) ZEST 12 months Stent TAXUS-Liberte # patients (871) (903) (884) MACE 11.0% 9.2% 8.3% TVR 8.0% 5.8% (ID-TVR: 5.4%) 5.2% TLR 5.0% (ID-TLR: 4.4%) 4.9% ST 0.8% 2.5% 0.7% # lesions (1205) LLL (mm) 0.41±0.54 0.46±0.52 Binary restenosis 11.38% 10.9%