1. The Randomized Comparison of 6-month vs
The Randomized Comparison of 6-month vs. 12-month Duration of Dual Antiplatelet Therapy after the Implantation of Drug Eluting Stent
Hyeon-Cheol Gwon, Joo Yong Hahn, Young Bin Song,
Kyung Woo Park, Yang Soo Jang, Hyo-Soo Kim,
On behalf of the EXCELLENT Trial Investigators
Samsung Medical Center, Sungkyunkwan University School of Medicine

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.
CONSULTING FEES/HONORARIA:
Cordis,
Medtronic Asia Pacific
RESEARCH/RESEARCH GRANTS:
Abbott Korea,
Medtronic Korea

3. Background
Current guidelines recommend at least 12 months of dual antiplatelet therapy after DES implantation
This recommendation is not based on any prospectively randomized data.
Prolonged duration of clopidogrel therapy in addition to aspirin may be associated with greater cost and higher risk of bleeding.

4. Objective of Study Hypothesis
To test the safety and efficacy of 6-month duration compared with 12-month duration of dual antiplatelet therapy (DAT) in addition to aspirin after the implantation of DES
Hypothesis
Six-month DAT is non-inferior to 12-month DAT
in terms of target vessel failure at 12 months

5. 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

6. Prospective, open label, two-arm, randomized multi-center trial
Trial Design
Prospective, open label, two-arm, randomized multi-center trial
DAT 6 months N=722
DAT 12 months N=721
1443 Patients Matching Enrollment Criteria
EES N=540
SES N=182
EES N=539
SES
N=182
Percutaneous Coronary Intervention
2x2 factorial design
1mo
3mo
9mo
12mo
Clinical
Angiographic
3yr
2yr
4yr
5yr
Primary clinical endpoint evaluation
Co-primary angiographic
endpoint evaluation
Am Heart J 2009 May;157: e1
gov (NCT ).

7. EXCELLENT RCT EES vs. SES
Presented at LBCT session in TCT 2010 by Dr. HS Kim

8. Study Endpoints Primary Endpoint 12-month target vessel failure (TVF)
a composite of cardiac death, MI, or TVR
Co-primary endpoint
In-segment late luminal loss (LL) at 9 months (for comparison of EES vs. SES)
Secondary Endpoints
All death, cardiac death
Myocardial infarction (MI)
Cerebrovascular accident (CVA)
Target lesion revascularization (TLR)
Target vessel revascularization (TVR)
Any revascularization
Stent thrombosis: definite or probable stent thrombosis by ARC definition
TIMI major bleeding: a drop in Hb > 5 g/dl or in Hct > 15%
Safety endpoint: death, MI, CVA, stent thrombosis, or TIMI major bleeding
Major adverse cardiocerebral event (MACCE): death, MI, CVA, or any revasc
* Definitions follow the ARC recommendations, if not described.

9. Sample Size Calculation
Primary Endpoint
12-month Target Vessel Failure (TVF)
TVF in 12-month DAT group: 10%
Non-inferiority design with non-inferiority margin 4%
Type I error 0.05, type II error 0.20
Sampling ratio 6-month:12-month = 1:1
Estimated drop out rate 5%
Total 1,372 patients needed

10. Independence in Trial Coordination
Executive Committee
(HS Kim, MD, YS Jang, MD, JH Yoon, MD,
HC Gwon, MD, IH Chae, MD, TH Ahn, MD)
DSMB
Data Safety
Monitoring Board
MRCC
Trial
Coordinating Center
CEAC
Clinical Event Adjudication Committee
Steering Committee
19 study investigators
Grant Support
1) Ministry of Health, Welfare, and Family Affairs of Korea
2) Abbott Vascular Korea
3) Boston Scientific Korea
The companies were not involved with the protocol development or the study process, including site selection, management, and data collection and analysis.

11. Participating Centers
19 Hospitals in Republic of Korea
Seoul National University Hospital
Yonsei University Severance Hospital
Samsung Medical Center
Seoul National University Bundang Hospital
Gachon University Gil Medical Center
Yonsei University Wonju Christian Hospital
Hallym University Sacred Heart Hospital
Kandgong Sacred Heart Hospital
Chonam National University Hospital
Gangnam Severance Hospital
NHIC Ilsan Hospital
Inje University Sanggye Paik Hospital
Korea University Anan Hospital
Pusan National University Hospital
Boramae Medical Center
Kangnam Sacred Heart Hospital
Uijeongbu St. Mary’s Hospital
Keimyung University Dongsan Hospital
Ewha Womans University Mokdong Hospital

12. Study flow Enrolled and Randomized (n=1,443) Allocated to 6-mo DAT
Allocated to 12-mo DAT (n=721)
Intention-to-treatment Analysis
Follow-up loss within 395 days n=6
Follow-up loss within 395 days n=9
6-mo DAT with 12-mo FU (n=716)
12-mo DAT with 12-mo FU (n=712)
12-mo event Analysis

13. Baseline Clinical Profiles
Variables ― no. (%)
6-mo DAT
(N=722)
12-mo DAT
(N=721)
p-value
Age (years)*
63.0±9.6
62.4±10.4
0.209
Males
470 (65.1)
461 (63.9)
0.646
Body mass index (kg/m2)*
24.9±3.1
25.1±3.0
0.324
Clinical diagnosis
0.560
Silent ischemia/ stable angina
353 (48.9)
346 (48)
Unstable angina/NSTEMI
350 (48.5)
349 (48.4)
STEMI
19 (2.6)
26 (3.6)
Diabetes mellitus
272 (37.7)
278 (38.6)
0.729
Chronic renal failure
6 (0.8)
9 (1.2)
0.435
Hypertension
525 (72.7)
532 (73.8)
Dyslipidemia
543 (75.2)
550 (76.3)
0.634
Current smoker
198 (27.4)
186 (25.8)
0.485
Family history of CAD
62 (8.6)
65 (9.0)
0.774
Previous myocardial infarction
47 (6.5)
27 (3.7)
0.017
Previous PCI
67 (9.3)
0.650
Previous CABG
11 (1.5)
7 (1.0)
0.344
Previous congestive heart failure
4 (0.6)
5 (0.7)
0.753
Cerebrovascular disease
48 (6.7)
0.910
Peripheral vascular disease
10 (1.4)
0.815
LV ejection fraction (%)*
61.0±9.6
61.6±9.4
0.297
Table 1
* Mean±SD

14. Angiographic and Procedural Profiles (per Patient)
Variables ― no. (%)
6-mo DAT
(N=722)
12-mo DAT
(N=721)
p-value
Angiographic disease extent
0.904
1-vessel disease
347 (48.1)
346 (48.0)
2-vessel disease
226 (31.3)
232 (32.2)
3-vessel disease
149 (20.6)
143 (19.8)
LAD location
442 (61.6)
440 (61.2)
0.861
Lesion type B2C
406 (57.2)
421 (59.1)
0.457
Total occlusion
14 (2.0)
11 (1.5)
0.540
Thrombotic lesion
73 (10.3)
70 (9.8)
0.778
Ulcerative lesion
23 (3.2)
16 (2.2)
0.258
Bifurcation lesion
227 (31.4)
247 (34.3)
0.255
No. of lesion treated per patient
1.40.6
1.30.6
0.173
No. of stents per patient
1.590.96
1.640.94
0.398
Use of GP IIb/IIIa inhibitor
12 (1.7%)
0.997
Use of IVUS
315 (43.6)
312 (43.3)
0.892
Table 1

15. Angiographic Profiles (per lesion)
Variables ― no. (%)
6-mo DAT
(N=957)
12-mo DAT
(N=970)
p-value
LAD location
467 (49.1)
459 (47.4)
0.473
ACC/AHA B2/C type
487 (52.8)
505 (53.7)
0.696
Long Lesion (≥ 20 mm)
353 (40.2)
373 (41.2)
0.664
Tortuous lesion
73 (7.9)
59 (6.3)
0.168
Total occlusion
14 (1.5)
11 (1.2)
0.514
Ulcerated lesion
23 (2.4)
16 (1.6)
0.240
Thrombotic lesion
74 (8.0)
73 (7.8)
0.835
Bifurcation lesion
236 (24.7)
272 (28.0)
0.092
Calcific lesion
186 (20.2)
194 (20.6)
0.803
Table 1

16. Procedural Profiles and QCA (per lesion)
Variables ― no. (%)
6-mo DAT
(N=957)
12-mo DAT
(N=970)
p-value
No. of stents per lesion
1.200.46
1.210.46
0.429
Max stent diameter  
3.210.42
3.190.42
0.315
Min stent diameter
3.080.41
3.060.43
0.287
Sum of stent length
27.813.0
28.313.7
0.362
Device success
941 (99.7)
963 (99.7)
0.977
Lesion success
964 (99.8)
0.636
Procedural success
935 (99.0)
956 (99.0)
0.857
Pre-PCI MLD
0.860.49
0.880.47
0.304
Pre-PCI RD
2.910.50
2.840.50
0.005
Lesion length
20.011.5
20.712.3
0.185
Post-PCI Instent MLD
2.630.46
2.580.47
0.330
Post-PCI Inseg MLD
2.260.51
2.190.51
0.003
Post-PCI RD
2.950.46
2.910.46
0.025
Table 1

17. Medications Variables ― no. (%) 6-mo DAT (N=722) 12-mo DAT (N=721)
p-value
Use of aspirin at 1 year
676 (99.9%)
667 (99.3%)
Duration of clopidogrel therapy
190 [ ]
375 [ ]
Clopidogrel duration
Less than due time*
Within due time*
More than due time*
No information
16 (2.2%)
501 (69.4%)
192 (26.6%)
13 (1.8%)
45 (6.2%)
442 (61.3%)
219 (30.4%)
15 (2.1%)
Clopidogrel restart within 1 year
34 (4.7%)
22 (3.1%)
Medications at discharge
Aspirin
707 (99.4)
704 (99.0)
0.364
Clopidogrel
702 (98.7)
708 (99.6)
0.082
Statin
604 (85.0)
582 (81.9)
0.117
ACE inhibitor
224 (31.5)
243 (34.2)
0.283
ARB
244 (34.3)
231 (32.5)
0.465
Beta blocker
427 (60.1)
445 (62.6)
0.327
Warfarin
6 (0.8)
13 (1.8)
0.106
Calcium channel blocker
238 (33.5)
249 (35.0)
0.539
Table 2
(*due time: 120~240 days in 6-mo DAT group, 300~420 days in 12-mo DAT group)

18. 12-month Clinical Event (Chi-square test) Variables ― no. (%) 6-mo DAT
RR (95% CI)
p-value
Total death
4 (0.6)
7 (1.0)
0.57 ( )
0.359
Cardiac death
2 (0.3)
3 (0.4)
0.66 ( )
0.650 MI
13 (1.8)
8 (1.1)
1.63 ( )
0.277
MI of target vessel
12 (1.7)
5 (1.0)
1.72 ( )
0.253
CVA
5 (0.7)
0.60 ( )
0.473
TLR
17 (2.4)
19 (2.7)
0.89 ( )
0.723
TVR
22 (3.1)
22 (3.2)
0.95 ( )
0.865
Any revascularization
41 (5.7)
43 (6.0)
0.95 ( )
0.802
Stent thrombosis
6 (0.8)
2.00 ( )
0.320
Any bleeding
10 (1.4)
0.39 ( )
0.105
TIMI major bleeding
0.50 ( )
0.409
Safety endpoint
24 (3.4)
1.09 ( )
0.779
TVF
34 (4.7%)
31 (4.4%)
1.10 ( )
0.721
MACCE
54 (7.5)
60 (8.4)
0.89 ( )
0.537
Table 2
Safety endpoint: death, MI, CVA, stent thrombosis, or TIMI major bleeding
TVF: cardiac death, MI, or TVR
MACCE: death, MI, CVA, or any revascularization

19. 12-month Target Vessel Failure
1˚ Endpoint
12-month Target Vessel Failure
(Kaplan-Meier Analysis)
Cumulative proportional TVF estimate at 1 year
6-mo DAT (N=1067)
5.2±0.8%
12-mo DAT (N=361)
4.3±0.8%
Pre-specified non-inferiority margin
4.0%
Difference
p=0.426
Non-inferiority
p=0.0031
Upper 1-sided 97.5% CI
Difference
Table 4: PP, all lesions
Non-inferior
0.9%
3.6%
-1.5
-1.0
-0.5
0.0
0.5
1.0
1.5
2.0
2.5
3.0
3.5
4.0
4.5 %

20. Cumulative incidence rate (%) Months after initial procedure
1˚ Endpoint
Target Vessel Failure
6-mo DAT
12-mo DAT
P=0.507
HR = 1.17 (95% CI )
4.7%
Cumulative incidence rate (%)
4.4%
Months after initial procedure
Patient Number at Risks
6-month
722
707
701
697
681
12-month
721
710
699
698
680

21. Target Vessel Failure (Landmark Analysis) ~ 6 months 6 months ~
1˚ Endpoint
Target Vessel Failure
(Landmark Analysis)
6-mo DAT
12-mo DAT
~ 6 months
6 months ~
P=0.563
HR = 1.25 (95% CI )
P=0.699
HR = 1.13 (95% CI )
Patient Number at Risks
6-month
722
707
701
12-month
721
710
699
Patient Number at Risks
701
697
681
699
698
680

22. Cumulative incidence rate (%) Months after initial procedure
Cardiac Death
6-mo DAT
12-mo DAT
P=0.533
HR = 0.58 (95% CI 0.10 – 3.23)
Cumulative incidence rate (%)
0.4%
0.3%
Months after initial procedure
Patient Number at Risks
6-month
722
707
701
697
681
12-month
721
710
699
698
680

23. Myocardial Infarction
6-mo DAT
12-mo DAT
P=0.280
HR = 1.62 (95% CI 0.67 – 3.93)
Cumulative incidence rate (%)
1.8%
1.1%
Months after initial procedure
Patient Number at Risks
6-month
722
707
701
697
681
12-month
721
710
699
698
680

24. Cumulative incidence rate (%) Months after initial procedure
Stent Thrombosis
(Definite or probable stent thrombosis by ARC definition)
6-mo DAT
12-mo DAT
P=0.426
HR = 1.68 (95% CI 0.47 – 6.06)
Cumulative incidence rate (%)
0.8%
0.4%
Months after initial procedure
Patient Number at Risks
6-month
722
707
701
697
681
12-month
721
710
699
698
680

25. Cumulative incidence rate (%) Months after initial procedure
TIMI Major Bleeding
(Overt clinical bleeding with a drop of Hb > 5 g/dl or Hct > 15%)
6-mo DAT
12-mo DAT
P=0.419
HR = 0.50 (95% CI 0.09 – 2.71)
Cumulative incidence rate (%)
0.6%
0.3%
Months after initial procedure
Patient Number at Risks
6-month
722
707
701
697
681
12-month
721
710
699
698
680

26. Cumulative incidence rate (%) Months after initial procedure
Safety Endpoint
(Death, MI, stent thrombosis, CVA, or TIMI major bleeding)
6-mo DAT
12-mo DAT
P=0.678
HR = 1.13 (95% CI 0.64 – 1.99)
Cumulative incidence rate (%)
3.4%
3.1%
Months after initial procedure
Patient Number at Risks
6-month
722
707
701
697
681
12-month
721
710
699
698
680

27. Cumulative incidence rate (%) Months after initial procedure
MACCE
(Death, MI, CVA, or any revascularization)
8.4%
P=0.896
HR = 0.98 (95% CI 0.68 – 1.40)
7.5%
Cumulative incidence rate (%)
6-mo DAT
12-mo DAT
Months after initial procedure
Patient Number at Risks
6-month
722
707
701
697
681
12-month
721
710
699
698
680

28. Subgroup Analysis N 6-mo DAT 12-mo Χ2 p-value Cox HR Cox P for
interaction
Age
< 65
761
19 (5.0%)
12 (3.2%)
0.202
0.115
0.127
 65
667
15 (4.5%)
19 (5.7%)
0.465
0.588
ACS* No
694
21 (6.9%)
14 (4.1%)
0.252
0.188
0.301
Yes
734
13 (3.6%)
17 (4.6%)
0.474
0.728
Diabetes
884
10 (2.2%)
23 (5.3%)
0.018
0.055
0.001
544
24 (8.9%)
8 (2.9%)
0.003
0.006
LVEF
< 50%
123
3 (3.0%)
4 (7.1%)
0.286
0.503
0.330
 50%
1086
26 (4.8%)
25 (4.6%)
0.833
0.607
Bifurcation
959
23 (4.7%)
20 (4.3%)
0.769
0.608
0.957
469
11 (4.9%)
11 (4.5%)
0.830
0.668
Stent
EES
1067
25 (4.7%)
27 (5.1%)
0.739
0.914
0.305
SES
361
9 (5.0%)
4 (2.2%)
0.149
0.168
Multi-stent
854
14 (3.2%)
12 (2.9%)
0.819
0.894
0.597
563
20 (7.5%)
19 (6.4%)
0.601
0.311
*ACS = unstable angina, NSTEMI, or STEMI 1 2 3
Favors 6-mo DAT
Favors 12-mo DAT

29. 12-month TVF in Stent Subgroups
(Kaplan-Meier Analysis)
Cumulative proportional TVF estimate at 1 year
Everolimus-eluting Stent
Sirolimus-eluting Stent
97.5%
6-mo DAT (N=540)
5.2±1.0%
12-mo DAT (N=539)
5.1±1.0%
Non-inferiority
p=0.0029
6-mo DAT (N=182)
5.0±1.6%
12-mo DAT (N=182)
2.2±1.1%
Non-inferiority
p=0.268
Pre-specified non-inferiority margin: 4.0%
Upper 1-sided
97.5% CI
Difference
Table 4: PP, all lesions
0.1%
2.9%
2.2%
6.6% -1 1 2 3 4 5 6 -1 1 2 3 4 5 6

30. Everolimus-eluting Stent Sirolimus-eluting Stent
TVF in Stent Subgroups
6-mo DAT
12-mo DAT
Everolimus-eluting Stent
Sirolimus-eluting Stent
p=0.914
HR = 1.03 ( )
p=0.168
HR = 2.29 ( )
5.0%
4.9%
4.6%
2.2%
Patient Number at Risks
6-mo
540
531
528
524
511
12-mo
539
521
505
Patient Number at Risks
6-mo
182
176
174
171
12-mo
179
178

31. Study flow: Per-protocol analysis
Enrolled and Randomized (n=1,443)
Allocated to 6-mo DAT
(n=722)
Allocated to 12-mo DAT (n=721)
Intention-to-treatment Analysis
Follow-up loss within 395 days (n=6)
Clopidogrel duration less than due time (n=14)
Clopidogrel duration more than due time (n=192)
No information about clopidogrel (n=13)
Follow-up loss within 395 days (n=9)
Clopidogrel duration less than due time (n=41)
Clopidogrel duration more than due time (n=219)
No information about clopidogrel (n=13)
DAT 6-mo with 12-mo FU (n=497, 68.8%)
DAT 12-mo with 12-mo FU (n=439, 60.9%)
Per-protocol Analysis
(*due time: 120~240 days in 6-mo DAT group, 300~420 days in 12-mo DAT group)

32. 12-month Target Vessel Failure by Per-protocol Analysis
Cumulative proportional TVF estimate at 1 year
6-mo DAT (N=497)
3.6±0.8%
12-mo DAT (N=439)
4.3±0.8%
Pre-specified non-inferiority margin
4.0%
Difference
p=0.158
Non-inferiority
p=0.0093
Upper 1-sided 97.5% CI
Difference
Table 4: PP, all lesions
Non-inferior
1.5%
3.6%
-1.5
-1.0
-0.5
0.0
0.5
1.0
1.5
2.0
2.5
3.0
3.5
4.0
4.5 %

33. Target Vessel Failure by Per-protocol Analysis
6-mo DAT
12-mo DAT
P=0.203
HR = 1.66 (95% CI 0.76 – 3.59)
Cumulative incidence rate (%)
3.2%
2.1%
Months after initial procedure
Patient Number at Risks
6-month
497
490
488
487
480
12-month
439
435
433

34. 12-month TVF in Stent Subgroups by Per-protocol Analysis
Cumulative proportional TVF estimate at 1 year
Everolimus-eluting Stent
Sirolimus-eluting Stent
6-mo DAT (N=377)
4.4±0.9%
12-mo DAT (N=332)
2.1±0.8%
Non-inferiority
p=0.013
6-mo DAT (N=120)
4.2±1.8%
12-mo DAT (N=107)
1.9±1.3%
Non-inferiority
p=0.222
Pre-specified non-inferiority margin: 4.0%
Upper 1-sided
97.5% CI
Difference
Table 4: PP, all lesions
1.3
3.7
2.3
6.7
Non-inferior -1 1 2 3 4 5 6 -1 1 2 3 4 5 6

35. TVF in Stent Subgroups by Per-protocol Analysis
Everolimus-eluting Stent
Sirolimus-eluting Stent
p=0.286
HR=1.65 ( )
p=0.332
HR=2.25 ( )
4.2%
2.9%
1.9%
2.1%
Patient Number at Risks
6-mo
377
373
371
365
12-mo
332
329
328
Patient Number at Risks
120
117
116
115
107
106
105

36. Study Limitations
The incidence of primary endpoint was lower than expected.
Underpowered to test hard endpoints of death, MI, or stent thrombosis.
Significant proportion of the patients crossed over to shorter or longer duration of clopidogrel therapy.
Longer term duration of follow-up is to be done.

37. Conclusions
Six-month DAT is non-inferior to 12-month DAT with regard to the risk of target vessel failure at 12 months after DES implantation.
In particular, the EES subgroup showed very similar event rates between the 6-month and 12-month DAT groups.
A larger-scale randomized controlled trial is required to test the impact of shorter duration of clopidogrel therapy on the hard endpoints of death, MI, or stent thrombosis.