1. The RESOLUTE Program: today and tomorrow
Sigmund Silber, MD, PhD FESC, FACC, FAHA
Professor of Medicine
Heart Center at the Isar
Munich, Germany

2. RESOLUTE Global Clinical Program Zotarolimus eluted from BioLinx™ durable polymer
Enrollment Complete - In Follow Up
RESOLUTE1
Non-RCT First-in-Human (R=139)
5 yr
RESOLUTE AC2,3
1:1 RCT vs. Xience V™ EES (R=1140; X=1152)
3 yr
RESOLUTE Int4
Non-RCT Observational (R=2349)
3 yr
RESOLUTE US5
2.25 – 4.0 mm Non-RCT vs. Hx Control (R=1402)
2 yr
RESOLUTE Japan
2.5 – 3.5 mm Non-RCT (R=100) vs. Hx Control
2 yr
RESOLUTE US
38 mm sub-study Non-RCT vs. PG (R=114)
1 yr
R-Japan SVS
2.25 Non-RCT vs. PG (R=65)
< 1yr
R-China RCT
1:1 RCT vs. Taxus™ PES (R=200; T=200)
< 1yr
RESOLUTE Asia
Non-RCT Observational (R=312)
< 1yr
R-China Registry
Non-RCT Observational (R=1800)
< 1yr
Enrolling / Planning
RI-US Registry
Post-approval study (R=230)
enrolling
1 Meredith IT, et al. EuroIntervention. 2010;5: Serruys PW, et al. N Engl J Med. 2010;363: Silber S, et al. Lancet. 2011;377: Neumann FJ, et al. EuroIntervention. 2012;7(10): Yeung AC, et al. JACC. 2011;57: 2

3. RESOLUTE All Comers Clinical Trial Design
Co-PIs: Profs. Serruys, Silber, Windecker
Open label, non-inferiority trial
Any patient with symptomatic coronary artery disease eligible for DES implantation
(no lesion/vessel limitations)
17 European sites
2300 patients randomized 1:1
Subsets: QCA 460 pts (20%); OCT 50 pts (2%)
100% monitoring
Resolute™ Stent
n = 1150
Xience V™ Stent
n = 1150
Clinical endpoints
30d
6mo
12mo
13mo
2yr
3yr
4yr
5yr
Angio/OCT endpoints
Primary Endpoint:
12-month target lesion failure (TLF), composite of cardiac death, target vessel MI & clinically driven TLR
Secondary Endpoints:
Clinical: Patient composite of any death, any MI, & any repeat revascularisation
QCA (powered): 13-month in-stent % diameter stenosis
QCA: % diameter stenosis, late loss, and binary restenosis
Drug Therapy: ASA and clopidogrel/ticlopidine > 6mo (per guidelines)
Serruys PW, Silber, S. et al., N Engl J Med. 2010;363(2):136-46

4. RESOLUTE All Comers Patient Eligibility Inclusion Criteria
Coronary artery disease
Stable angina
Silent ischemia
Acute coronary syndrome including UA, NSTEMI and STEMI
Lesion characteristics
Number of lesions : no limitation
Number of vessels : no limitation
Lesion length : no limitation
Written informed consent
Exclusion Criteria
Known intolerance to
Aspirin, clopidogrel, heparin, cobalt alloy, everolimus, zotarolimus, contrast material, polymer coating
Planned, elective surgery within 6 months of PCI
Unless dual anti-platelet therapy could be maintained
Pregnancy
Participation in another trial
Serruys PW, Silber, S. et al., N Engl J Med. 2010;363(2):136-46

5. RESOLUTE All Comers Baseline Characteristics Resolute™ ZES (N = 1140)
Xience V™ EES
(N = 1152)
P value
Age (yr)
64.4 ± 10.9
64.2 ± 10.8
0.70
Men (%)
76.7
77.2
0.80
Diabetes mellitus (%)
23.5
23.4
1.00
IDDM
8.4
7.1
0.28
ACS (%)
48.3
47.7
AMI (within 12 hr) (%)
15.4
17.8
0.13
AMI (within 72 hr) (%)
28.9
28.8
0.96
Multivessel disease (%)
58.4
59.2
0.73
Small vessel (RVD ≤2.75 mm)
67.8
67.4
0.88
Long lesion (length >18 mm)
18.2
21.2
0.11
Bifurcation/trifurcation (%)
16.9
17.7
0.62
Total occlusion (%)
16.3
17.2
0.61
In-stent restenosis (%)
8.1
8.0
0.94
Complex Patients1 (%)
67.0
65.6
0.51
1Complex patient definition: bifurcation, bypass grafts, ISR, AMI <72 hr, LVEF <30%, unprotected LM, >2 vessels stented, renal insufficiency or failure (creatinine >140 µmol/L), lesion length >27 mm, >1 lesion per vessel, lesion with thrombus or TO (preprocedure TIMI = 0). Resolute Integrity DES is not specifically approved for the following patients subsets; bypass graft, LVEF<30%, unprotected LM and renal insufficiency or failure (creatinine>140µmol/L) .
Serruys PW, Silber, S. et al., N Engl J Med. 2010;363(2):136-46

6. RESOLUTE All Comers Procedure Characteristics Resolute™ ZES
N = 1140 patients,
1661 lesions
Xience V™ EES
N = 1152 patients,
1705 lesions
P value
Lesions treated per patient
1.46 ± 0.73
1.48 ± 0.77
0.46
Lesion length (mm)
11.89 ± 7.50
12.15 ± 7.86
0.38
No. of stents per patient
1.9 ± 1.2
2.0 ± 1.3
0.02
Stent length per patient (mm)
34 ± 24
37 ± 26
Pre-stent balloon dilatation
69.5%
70.2%
0.75
Deployment pressure
14.85 ± 3.14
15.10 ± 3.20
0.01
Implantation of study stent only
98.0%
96.9%
0.11
Lesion success
98.9%
99.1%
0.62
Device success
97.0%
96.6%
0.52
Procedure success
94.6%
94.2%
0.78
Serruys PW, Silber, S. et al., N Engl J Med. 2010;363(2):136-46

7. RESOLUTE All Comers Target Lesion Failure – Primary Endpoint 8.3% 8.2%
Resolute™ ZES (N = 1140)
20%
Xience V™ EES (N = 1152)
Log rank P = 0.92
15%
Cumulative Incidence of Events
10%
8.3%
Primary endpoint
Pnon-inferiority <0.001
8.2% 5% 0% 12 24 36
Time after Initial Procedure (months)

8. Cumulative Incidence of Events Time after Initial Procedure (months)
RESOLUTE All Comers
Target Lesion Failure to 3 Years
Resolute™ ZES (N = 1140)
20%
Xience V™ EES (N = 1152)
Log rank P = 0.65
HR 1.05 [0.84, 1.33]
15%
13.1%
12.4%
Cumulative Incidence of Events
10% 5% 0% 12 24 36
Time after Initial Procedure (months) 8

9. RESOLUTE All Comers Components of Target Lesion Failure at 3 Years
Resolute™ ZES (n = 1120)
Xience V™ EES (n = 1130)
P = 0.43
0.7% [-0.9%, 2.2%]
P = 0.77
0.3% [-1.5%, 2.1%]
P = 0.86
0.2% [-1.7%, 2.2%]
Events (%)
Cardiac Death
TV-MI
TLR

10. RESOLUTE All Comers Stent Thrombosis (Definite/Probable) to 3 Years
Resolute™ ZES (N = 1140)
Log rank P = 0.10
15%
Xience V™ EES (N = 1152)
10%
Cumulative Incidence of
ARC Definite/Probable ST 5%
2.1%
1.3% 0% 1 2 3
Time After Initial Procedure (Years)
RESOLUTE All Comers was not specifically designed or powered for the analysis shown above.

11. RESOLUTE All Comers
Very Late Stent Thrombosis (Definite/Probable) 1-3 Years 3%
Resolute™ ZES (N = 1140)
Xience V™ EES (N = 1152) 2%
Cumulative Incidence of
ARC Definite/Probable ST
Log rank P = 1.00 1%
0.56%
0.55% 0% 1 2 3
Time After Initial Procedure (Years)
Patients at Risk
RZES
1140
1108
1081
CI%
0.00
0.27
0.55
EES
1152
1107
1083
0.56
RESOLUTE All Comers was not specifically designed or powered for the analysis shown above.

12. RESOLUTE Global Clinical Program Zotarolimus eluted from BioLinx™ durable polymer
Enrollment Complete - In Follow Up
RESOLUTE1
Non-RCT First-in-Human (R=139)
5 yr
RESOLUTE AC2,3
1:1 RCT vs. Xience V™ EES (R=1140; X=1152)
3 yr
RESOLUTE Int4
Non-RCT Observational (R=2349)
3 yr
RESOLUTE US5
2.25 – 4.0 mm Non-RCT vs. Hx Control (R=1402)
2 yr
RESOLUTE Japan
2.5 – 3.5 mm Non-RCT (R=100) vs. Hx Control
2 yr
RESOLUTE US
38 mm sub-study Non-RCT vs. PG (R=114)
1 yr
R-Japan SVS
2.25 Non-RCT vs. PG (R=65)
< 1yr
R-China RCT
1:1 RCT vs. Taxus™ PES (R=200; T=200)
< 1yr
RESOLUTE Asia
Non-RCT Observational (R=312)
< 1yr
R-China Registry
Non-RCT Observational (R=1800)
< 1yr
Enrolling / Planning
RI-US Registry
Post-approval study (R=230)
enrolling
1 Meredith IT, et al. EuroIntervention. 2010;5: Serruys PW, et al. N Engl J Med. 2010;363: Silber S, et al. Lancet. 2011;377: Neumann FJ, et al. EuroIntervention. 2012;7(10): Yeung AC, et al. JACC. 2011;57: 12

13. 5130 Resolute™ ZES population
RESOLUTE Pooled Diabetic Analysis
Diabetic vs. Non-Diabetic Patient Populations
RESOLUTE
139
RESOLUTE AC
1140
RESOLUTE Int
2349
RESOLUTE US
1402
RESOLUTE Japan
100
5130 Resolute™ ZES population
Total diabetic patient population
N = 1535
Matched cohort diabetic population
N = 878 (less complex patients)
“Standard risk” diabetic patient cohort
pre-specified for FDA indication
Matched cohort is all enrolled diabetic subjects excluding subjects with bifurcation, saphenous vein graft (SVG), ISR, AMI (≤72 hours), left ventricular ejection fraction (LVEF) <30%, an unprotected left main lesion, ≥3 vessels, renal impairment (creatinine ≥ 140µmol/L), total lesion length per vessel >27 mm, ≥2 lesions per vessel, lesion with thrombus, or lesion with total occlusion.
Silber S. et al, JACC Intv, 2013, (in press) 13

14. RESOLUTE Pooled Diabetic Analysis
FDA Indication for Patients with Diabetes Mellitus
Prespecified diabetes analysis designed with FDA for diabetes indication Performance goal prespecified based on meta-analysis: DIABETES, RAVEL DM, SIRIUS DM, TAXUS IV, SCORPIUS, ENDEAVOR Pooled DM. Standard risk patient population from Pooled RESOLUTE matched to performance goal patient population
TVF at 12 Months
(powered endpoint)
P = 0.001
14.5
Events (%)
7.8
Performance Goal
Resolute™ DES†
TVF: target vessel failure (cardiac death, TV-MI, and clinically driven TVR)
†RESOLUTE matched cohort diabetes pooled analysis (N = 878).
Silber S. et al, JACC Intv, 2013, (in press)

15. Standard Risk Diabetics N = 878
RESOLUTE Pooled Diabetic Analysis
Baseline Characteristics: All Diabetic Patients, incl. Complex %
Standard Risk Diabetics N = 878
All Diabetics
N = 1535
Age (yr)
65.2 ± 10.2
65.6 ± 10.2
Male
66.4
68.1
Diabetes mellitus
100.0
IDDM
28.5
29.6
Prior MI
24.9
27.6
Prior PCI
34.6
34.5
Reason for Revascularization:
Stable angina
46.2
39.7
Unstable angina
28.9
26.8
Myocardial infarction
5.4
18.1
LAD
44.8
46.8
RVD (mm)
2.7 ± 0.5
Lesions per patient
1.1 ± 0.4
1.3 ± 0.6
Stent length per patient
22.5 ± 11.3
28.5 ± 18.8
Complex patients*
42.8
* Complex patient definition: bifurcation, bypass grafts, ISR, AMI <72 hr, LVEF <30%, unprotected LM, >2 vessels stented, renal insufficiency or failure (creatinine >140 µmol/L), lesion length >27 mm, >1 lesion per vessel, lesion with thrombus or TO (preprocedure TIMI = 0).
Silber S. et al, JACC Intv, 2013, (in press)

16. Cumulative Incidence of TLF Time After Initial Procedure (months)
RESOLUTE Pooled Diabetic Analysis
All Patients – Target Lesion Failure to 2 Years
20%
Non-Diabetics (N = 3595)
All Diabetics (N = 1535)
15%
11.2%
Cumulative Incidence of TLF
10%
7.7%
8.4% 5%
6.1% 0% 6 12 18 24
Time After Initial Procedure (months)
No. at risk
Non-Diabetics
3595
3540
3399
3301
3198
Diabetics
1535
1518
1447
1386
1345
The RESOLUTE Pooled analysis was not specifically designed or powered for the analysis shown above.
Silber S. et al, JACC Intv, 2013, (in press)

17. RESOLUTE Pooled Diabetic Analysis
Baseline Characteristics: ITDM = Insulin Treated Diabetes Mellitus %
Non-Diabetics
N = 3595
Non-ITDM
N = 1080
ITDM
N = 455
Age (yr)
63.1 ± 11.2
65.8 ± 10.2*
65.2 ± 10.1
Male
77.8
71.9*
59.3**
Diabetes mellitus
100.0*
100.0
IDDM
100.0**
Hypertension
67.8
84.6*
90.3**
Hyperlipidemia
67.7
80.0*
81.8
Current smoker
26.0
19.7*
14.7**
Family history
38.1
34.0*
37.6
Prior MI
25.9
26.7
29.8
Prior PCI
29.3
32.7*
38.9**
Prior CABG
7.4
11.2*
11.2
Clinical status: *
Stable angina
38.0
40.2
38.5
Unstable angina
25.5
26.2
28.1
Myocardial infarction
24.3
17.8
18.9
*p-value <0.05 Non-IDDM vs. Non-Diabetics ** p-value <0.05 IDDM vs Non-IDDM
The RESOLUTE Pooled analysis was not specifically designed or powered for the analysis shown above.
Silber S. et al, JACC Intv, 2013, (in press)

18. Cumulative Incidence of TLR Time After Initial Procedure (months)
RESOLUTE Pooled Diabetic Analysis
All Patients – Target Lesion Revascularization to 2 Years
20%
Non-Diabetics (N = 3595)
Diabetics Non-ITDM (N = 1080)
Diabetics ITDM (N = 455)
15%
10%
Cumulative Incidence of TLR
9.0%
6.3% 5%
4.7%
4.3%
3.0%
3.0% 0% 6 12 18 24
Time After Initial Procedure (months)
No. at risk
Non-Diabetics
3595
3589
3479
3385
3285
Non-IDDM
1080
1078
1046
1007
985
IDDM
455
454
428
409
389
Error bars indicate a point-wise two-sided 95% confidence interval (±1.96*SE). Standard Error based on the Greenwood Formula.
Silber S. et al, JACC Intv, 2013, (in press)

19. RESOLUTE Pooled Diabetic Analysis
All Patients – Cardiac Death/TVMI to 2 Years
20%
Non-Diabetics (N = 3595)
Diabetics Non-ITDM (N = 1080)
Diabetics ITDM (N = 455)
15%
Cumulative Incidence of Cardiac Death/TVMI
10%
9.6%
6.6% 5%
5.2%
4.9%
3.8%
3.5% 0% 6 12 18 24
Time After Initial Procedure (months)
No. at risk
Non-Diabetics
3595
3543
3442
3387
3306
Non-IDDM
1080
1075
1041
1017
1005
IDDM
455
445
423
416
400
Error bars indicate a point-wise two-sided 95% confidence interval (±1.96*SE). Standard Error based on the Greenwood Formula.
Silber S. et al, JACC Intv, 2013, (in press)

20. RESOLUTE Pooled Diabetic Analysis
All Patients – ARC Def/Prob Stent Thrombosis to 2 Years
10%
Non-Diabetics (N = 3595)
Diabetics Non-ITDM (N = 1080)
Diabetics ITDM (N = 455) 8% 6%
Cumulative Incidence of ARC Def/Prob ST 4%
1.6 %
0.8 % 2%
0.7 %
1.8 %
0.9 %
0.8 % 0% 6 12 18 24
Time After Initial Procedure (months)
No. at risk
Non-Diabetics
3595
3590
3522
3471
3396
Non-IDDM
1080
1078
1054
1032
1020
IDDM
455
454
437
431
417
Error bars indicate a point-wise two-sided 95% confidence interval (±1.96*SE). Standard Error based on the Greenwood Formula.
Silber S. et al, JACC Intv, 2013, (in press)

21. RESOLUTE Global Clinical Program Zotarolimus eluted from BioLinx™ durable polymer
Take Home Messages:
In an all-comer patient population, the Resolute ZES and Xience V EES remained clinically equivalent through 3 years (TLF 13.1% vs. 12.4, P = 0.65).
The incidence of very late stent thrombosis rate is low and similar between Resolute ZES and Xience V EES (definite ST 0.3% vs. 0.5%, P = 0.48).
In patients with diabetes, the Resolute ZES is safe and effective. Patients with diabetes not taking insulin had similar clinical outcomes as patients without diabetes.
But for patients with diabetes who are taking insulin, continued attention is needed and bypass surgery should be considered as an alternative.