1. Efficacy of Xience/Promus versus Cypher to rEduce Late Loss in stENT
Hyo-Soo Kim MD, PhD
on behalf of the investigators
Seoul National University Hospital, Seoul, Korea

2. General Exclusion Criteria Angiographic Exclusion Criteria
Patient Eligibility
Inclusion Criteria
> 50% stenosis by visual estimation
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
2.25mm ≤ RVD ≤ 4.25mm
Lesion length: no limitation
Multiple stenting: no limitation
General Exclusion Criteria
GI or GU bleeding ≤3 months, major surgery ≤ 2 months
Hb<10 g/dL, PLT<100K
Elective surgical procedure planned ≤ 12 months
LVEF < 25%, or in shock
MI ≤ 72 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
Patients with significant LM stenosis
BMS or DES ISR
CTO
True bifurcation lesions requiring two stents

3. Trial Design
Prospective, open label, two-arm, randomized multi-center trial
1372 Patients Matching Enrollment Criteria
19 centers in Korea
Everolimus-Eluting Stent N=1029
Randomization
3:1
Sirolimus-Eluting Stent N=343
DAT 6 mo N=515
DAT 12 mo N=514
2x2 factorial design
DAT 6 mo N=171
DAT 12 mo N=172
Percutaneous Coronary Intervention
1mo
3mo
9mo
12mo
Clinical
Angiographic
3yr
2yr
4yr
5yr
Secondary clinical endpoint evaluation
Primary endpoint:
In-segment LL
Am Heart J 2009 May;157: e1.

4. Study Flow: Angiographic F/U
Enrolled and randomized
(N=1443)
EES N=1079
Randomized
3:1
SES N=364
Did not receive allocated stent: 24
- DES: 17
- BMS: 2
- CABG: 1
- POBA: 1
- Not inserted: 3
Failed PCI: 1
Did not receive allocated stent : 29
- DES: 23
- BMS: 0
- CABG: 1
- POBA: 1
- Not inserted: 4
Failed PCI: 0
Received EES
(1054 Pts, 1388 Lesions)
Received SES
(335 Pts, 414 Lesions)
Angiographic F/U (67.3%)
709 Pts, 949 Lesions
Angiographic F/U (64.5%)
216 Pts, 267 Lesions

5. Baseline Profiles Variables ― no. (%) EES (N=1,079) SES (N=364)
p-value
Age, years ― mean±SD
62.5±10.1
63.4±9.9
0.125
Males
703 (65.2)
228 (62.6)
0.386
Body-mass index, kg/m2
25±3.1
25±2.9
0.885
Diabetes mellitus
402 (37.3)
148 (40.7)
0.248
Chronic renal failure
12 (1.1)
3 (0.8)
0.773
Hypertension
790 (73.2)
266 (73.1)
0.959
Dyslipidemia
820 (76.0)
269 (73.9)
0.422
Current smoker
278 (25.8)
106 (29.1)
0.210
Family history of CAD
99 (9.2)
28 (7.7)
0.388
Previous myocardial infarction
56 (5.2)
17 (4.7)
0.696
Previous percutaneous coronary intervention
30 (8.2)
0.589
Previous bypass surgery
6 (1.6)
0.419
Previous congestive heart failure
8 (0.7)
1 (0.3)
0.463
Cerebrovascular disease
57 (5.3)
37 (10.2)
0.001
Peripheral vascular disease
13 (1.2)
0.594
Table 1 5

6. Baseline Profiles Variables ― no. (%) EES (N=1,079) SES (N=364)
p-value
Multivessel disease
564 (52.3)
185 (50.8)
0.633
Left ventricular ejection fraction, %
61.4±9.4
60.8±9.8
0.335
Clinical indication
0.115
Silent ischemia
39 (3.6)
16 (4.4)
Chronic stable angina
472 (43.7)
172 (47.3)
Unstable angina
464 (43.0)
139 (38.2)
NSTEMI
76 (7.0)
20 (5.5)
STEMI
28 (2.6)
17 (4.7)
Medications at discharge
Aspirin
1,066 (99.3)
356 (98.9)
0.510
Clopidogrel
1,063 (99.0)
357 (99.2)
1.000
Statin
892 (83.1)
304 (84.4)
0.539
ACE inhibitor
355 (33.1)
119 (33.1)
Angiotensin II-receptor antagonist
356 (33.1)
122 (33.9)
0.796
Beta-blocker
665 (61.9)
214 (59.4)
0.404
Calcium-channel blocker
362 (33.7)
128 (35.6)
0.522
Table 1 6

7. Lesion and Procedural Profiles
Variables ― no. (%)
EES
(N=1,458)
SES
(N=468)
p-value*
Location
0.815
Left anterior descending
722 (49.7)
235 (50.4)
Left circumflex
319 (22)
101 (21.7)
Right coronary
411 (28.3)
130 (27.9)
Coronary graft
1 (0.1)
0 (0)
Multivessel disease**
564 (52.3)
185 (50.8)
0.633
ACC-AHA B2/C type
746 (53.0)
245 (54.2)
0.632
Total occlusion
48 (3.4)
18 (4)
0.583
Thrombus-containing
114 (8.1)
33 (7.3)
0.567
Bifurcation lesions
166 (11.4)
50 (10.7)
0.728
Calcification
589 (41.8)
183 (40.4)
0.628
Minimal luminal diameter, mm
0.87±0.48
0.88±0.5
0.678
Reference vessel diameter, mm
2.87±0.49
2.88±0.52
0.641
Diameter stenosis, %
69.67±15.34
69.64±15.39
0.955
Lesion length, mm
20.32±12.05
20.48±11.51
0.812
Lesion length > 20mm
544 (40.2)
182 (41.9)
0.562
Table 2
*comparisons were performed using the generalized estimating equations (GEE).
**compared with the Chi-square t-test 7

8. Lesion and Procedural Profiles
Variables ― no. (%)
EES
(N=1,458)
SES
(N=468)
p-value*
No. of stents per lesion
1.21±0.47
1.19±0.42
0.311
No. of stents per patient†
1.64±0.97
1.53±0.87
0.049
Total stent length per lesion ― mm
27.86±13.42
28.55±13.22
0.375
Total stent length per patient†
37.7±24.89
36.85±24.87
0.410
Use of GpIIb/IIIa inhibitors**
19 (1.8)
5 (1.4)
0.617
Minimal luminal diameter (in stent)
2.6±0.46
2.6±0.49
0.848
Minimal luminal diameter (in segment)
2.22±0.51
2.24±0.53
0.554
Diameter stenosis (in stent)
8.59±8.95
8.3±8.3
0.451
Diameter stenosis (in segment)
19.01±11.07
18.37±11.19
0.238
Acute gain (in stent)
1.73±0.54
1.72±0.53
0.753
Acute gain (in segment)
1.35±0.58
1.35±0.57
0.877
Use of intravascular ultrasound (IVUS)*
466 (43.2)
160 (44)
0.798
Lesion success
1444 (99.7)
460 (99.8)
0.817
Device success
1446 (99.9)
457 (99.1)
0.100
Procedure success
1433 (99.0)
0.928
Table 2
*comparisons were performed using the generalized estimating equations (GEE).
**compared with the Chi-square test, and †with the independent t-test 8

9. QCA Data(1) :all lesions
Variables ― no. (%)
EES
(N=949)
SES
(N=267)
p-value*
Before procedure
Lesion length ― mm
20.34±11.80
20.89±11.44
0.512
Reference vessel diameter ― mm
2.86±0.49
2.86±0.52
0.937
Minimal luminal diameter― mm
0.87±0.47
0.83±0.47
0.278
Diameter stenosis ― %
69.57±15.14
71.02±14.83
0.178
Immediately after procedure
Minimal luminal diameter ― mm
In stent
2.60±0.45
2.59±0.48
0.796
In segment
2.22±0.51
2.21±0.52
0.968
8.57±8.94
8.30±8.63
0.577
19.13±11.30
18.42±10.82
0.322
Acute gain ― mm
1.73±0.54
1.76±0.54
0.526
1.35±0.57
1.38±0.56
0.364
Table 3-1
*comparisons were performed using the generalized estimating equations (GEE). 9

10. QCA Data(1) :all lesions
Variables ― no. (%)
EES
(N=949)
SES
(N=267)
p-value*
Follow-up at 9 months
Minimal luminal diameter ― mm
In stent
2.42±0.53
2.44±0.55
0.458
In segment
2.12±0.52
2.16±0.53
0.256
Diameter stenosis ― %
14.63±13.33
13.94±12.10
0.415
22.53±13.81
21.02±12.72
0.079
Late luminal loss ― mm
0.19±0.33
0.15±0.33
0.082
0.10±0.36
0.05±0.34
0.051
Binary restenosis ― %
18 (1.9)
3 (1.1)
0.293
30 (3.2)
6 (2.3)
0.352
Restenosis pattern** ― %
1.000
Focal
27 (90.0)
6 (100.0)
Diffuse
1 (3.3)
0 (0.0)
Proliferative
Total occlusion
Table 3-1
*comparisons were performed using the generalized estimating equations (GEE).
**compared with the Fishcer’s exact test 10

11. Non-inferiority p-value
1˚ Endpoint
In-segment late LL
EES (N=935)
0.10±0.36 mm
SES (N=266)
0.05±0.34 mm
Mean ΔLL: mm
Upper 1-sided 95% CI: mm
Non-inferiority p-value
0.023
Prespecified non-inferiority margin: 0.1 mm
Non-inferior
Table 4: PP, all lesions
-0.01
0.00
0.01
0.02
0.03
0.04
0.05
0.06
0.07
0.08
0.09
0.10
0.11 mm
Upper 1-sided 95% CI 11

12. Minimal Luminal Diameters
1˚ Endpoint
In-Sement
Minimal Luminal Diameters 20 40 60 80
100
Before Procedure
EES
SES
9-month F/U
EES
SES
After Procedure
EES
SES
% of Lesions
0.0
1.0
2.0
3.0
4.0
Minimal Luminal Diameter (mm)

13. In-segment & in-stent LL : long lesion or DM subgroup
Variables
EES
SES
Total
Mean ΔLL
(EES-SES)
Upper 1-sided 95% CI
p-value
1˚Endpoint: In-segment LLL
935
266
1,201
0.0507
0.0912
0.023
Long lesion (≥ 20mm)
369
111
480
0.0344
0.0962
0.041 DM
359
109
468
0.1105
0.1746
0.620
Post-hoc: in-stent LLL
0.0431
0.0811
0.007
0.0328
0.0920
0.031
0.1230
0.1824
0.765
Table 4 13

14. Cumulative incidence rate (%) Months after initial procedure
2˚ Endpoint
Hard Endpoints
: Composite of cardiac death, or MI
0.0
2.0
4.0
1.0
3.0
Log-Rank p-value=0.561
Cumulative incidence rate (%)
SES: 1.9%
EES: 1.5% 3 6 9 12
Months after initial procedure
Patient Number at Risks
EES
1078
1066
1064
1055
1052
SES
363
356
355
354

15. Cumulative incidence rate (%) Months after initial procedure
2˚ Endpoint
Soft Endpoints
TLR
0.0
2.0
4.0
1.0
3.0
5.0
Log-Rank p-value=0.400
EES: 2.4%
Cumulative incidence rate (%)
SES: 1.7% 3 6 9 12
Months after initial procedure
Patient Number at Risks
EES
1078
1066
1060
1043
1029
SES
363
356
355
351
350

16. Cumulative incidence rate (%) Months after initial procedure
2˚ Endpoint
Target Lesion Failure
: Composite of cardiac death, MI, or ID-TLR
0.0
2.0
4.0
1.0
3.0
5.0
Log-Rank p-value=0.552
EES: 3.7%
Cumulative incidence rate (%)
SES: 3.0% 3 6 9 12
Months after initial procedure
Patient Number at Risks
EES
1078
1066
1060
1043
1029
SES
363
356
355
351
350

17. : Composite of cardiac death, MI, or ID-TLR
2˚ Endpoint
Target Lesion Failure
: Composite of cardiac death, MI, or ID-TLR
Subgroups
Pt No.
Relative Risk (95% CI)
Int P DM
Yes
(N=542)
0.423 No
(N=874)
Age
≥ 70
(N=371)
0.952
< 70
(N=1045)
Lesion length (mm)
> 20
(N=622)
0.552
≤ 20
(N=794)
CCR (mg/dL)
≥ 60
(N=243)
0.699
< 60
(N=1173)
Multivessel ds
(N=735)
0.985
(N=681)
ACS
(N=728)
0.049
(N=688)
Overall
(N=1416)
0.527
0.25
0.5 1 2 4 8
Favors EES
Favors SES

18. Cumulative incidence rate (%) Months after initial procedure
2˚ Endpoint
Stent Thrombosis
: Definite/Probable ST by ARC definition
0.0
0.4
0.8
0.2
0.6
1.0
SES: 0.8%
Log-Rank p-value=0.281
Cumulative incidence rate (%)
EES: 0.4% 3 6 9 12
Months after initial procedure
Patient Number at Risks
EES
1078
1077
1071
1057
1043
SES
363
361
360
356
355

19. Myocardial Infarction
2˚ Endpoint
Myocardial Infarction
MI, total
p=1.000
MI,
peri-procedural
p=0.741
MI,
spontaneous
p=0.379
EES
N=1,057
SES
N=359
EES
N=1,057
SES
N=359
EES
N=1,057
SES
N=359

20. Summary : EXCELLENT-RCT
The efficacy of EES was non-inferior to SES in inhibiting late loss at 9 months & clinical events at 12 months.
The incidence of ST was not different between EES and SES although numerically lower in EES.
Tendency of higher late-loss in EES than SES may lead to the intriguing reciprocal trend between soft versus hard endpoints : higher incidence of TLR but lower incidence of death, MI, or ST.
 should be confirmed in the larger study in the future
Long term follow up will tell us whether Xience/Promus will offer similar efficacy along with better long term safety compared with the best 1st generation DES, Cypher.