1. 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

2. 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

3. 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

4. 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

5. 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

6. 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

7. 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

8. 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 Taxus LiberteTM)
Secondary Endpoint
: Late Luminal Loss (LLL) at 9 Months
LLL of Taxus LiberteTM: 0.400±0.500 mm (assumed)
Noninferiority margin: 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 Taxus LiberteTM)

9. 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

10. 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 ( ) Patients Analyzed According to ITT

11. 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

12. 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

13. 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

14. Clnically Driven Target Vessel Revascularization
1˚ Endpoint
Clnically Driven Target Vessel Revascularization 30
HR: 2.43 ( )
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

15. 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

16. 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

17. 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

18. 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

19. 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

20. 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).

21. 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: mm
Upper 95% CI: mm
Lower 95% CI: mm
Inferiority p-value
<0.001
Predefined non-inferiority margin: 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

22. Late Luminal Loss In-stent In-segment Coroflex Taxus Coroflex Taxus
0.710±0.64 vs ±0.50
(p<0.001)
0.480±0.61 vs ±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)

23. 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.

24. Thank You For Your Attention

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

26. 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%

27. 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%