1. 12 Month Outcomes in Patients with Diabetes Mellitus Implanted with a Resolute Zotarolimus-eluting Stent: Initial Results from the RESOLUTE Global Clinical Program
Stephan Windecker
On behalf of the RESOLUTE Clinical Program Investigators
Swiss Cardiovascular Center and Clinical Trials Unit Bern
Bern University Hospital, Switzerland

2. Potential conflicts of interest
Speaker’s name: Stephan Windecker MD
 I have the following potential conflicts of interest to report:
 Research contracts  Consulting
 Employment in industry
 Stockholder of a healthcare company
 Owner of a healthcare company
 Other(s)
 I do not have any potential conflict of interest 2

3. Background
While drug eluting stents (DES) are often used in complex patient and lesion cohorts the amount of data on current generation DES in this patient cohort is limited.
Resolute All Comers is an unrestricted open label trial that provides the ability to assess the outcomes in both the more well studied simple patient cohort and the more complex, higher risk patient cohort.

4. Baseline Patient and Lesion Characteristics
Resolute All Comers Complex Versus Simple Patients
Variable, %
Complex
n = 1520
Simple
n = 772 pts
P value
Age, years (Mean+SD)
63.9±11.1
65.1±10.3
0.009
Men
78.9
72.9
0.001
Diabetes mellitus
23.1
24.2
0.566
Hypertension
70.0
73.6
0.079
Hyperlipidemia
63.2
71.2
<0.001
Current smoker
29.5
20.6
Prior myocardial infarction
29.9
0.845
Prior PCI
32.4
31.1
0.538
Prior coronary artery bypass grafting
10.9
7.6
0.014
Current revasc for UA/MI
33.7
LAD
51.1
49.7
Lesion Length (mm)
12.4±8.6
11.3±5.1
RVD (mm)
2.6±0.6
2.6±0.5
0.216
Diameter Stenosis
65.8±19.7
58.7±12.5
B2/C
79.5
66.9
Stefanini G et al. J Am Coll Cardiol 2011, in press 4 4

5. RESOLUTE All Comers – Complex Patients
Clinical Outcomes to 12 Months
R-ZES EES
(n=764) (n=756)
Percentage [%]
Cardiac
Death
ARC ST
Def/Prob
Death
TV-MI
CD/TV-MI
CI-TLR
P=0.02
P=0.24
P=0.90
P=0.58
P=0.26
P=0.80 5

6. RESOLUTE All Comers – Simple Patients
Clinical Outcomes to 12 Months
R-ZES EES
(n=376) (n=396)
Percentage [%]
Cardiac
Death
ARC ST
Def/Prob
Death
TV-MI
CD/TV-MI
CI-TLR
P=0.79
P=0.50
P=0.70
P=0.48
P=0.12
P=0.49 6

7. The Impact of Patient and Lesion Complexity on Outcomes in the RESOLUTE AC Trial
Target Lesion Failure
10%
ZES Simple
ZES Complex
9.8
8.9
EES Simple
EES Complex 8%
6.8 6%
5.6
Cumulative Incidence Patient Oriented Composite 4% 2% 0% 30 60 90
120
150
180
210
240
270
300
330
360
Time after Initial Procedure (days)
No. at Risk
EES Complex
756
703
693
677
662
738
701
698
686
667
670
709
ZES Complex
764
723
709
696
685
744
718
711
708
692
693
703
725
EES Simple
396
377
375
369
357
385
376
365
368
370
379
ZES Simple
376
353
351
346
340
366
352
350
345
348
359
Stefanini G et al. J Am Coll Cardiol 2011, in press

8. Diabetic Patient Analysis
The ability to assess outcomes in broad patient populations such as simple or complex is possible from a single randomized trial such as Resolute All Comers, however for assessment of more specific sub-groups such as diabetics the prospective analysis from a broader pooled patient data set may allow for more clarity and confidence in reported outcomes.
Patients with diabetes are of particular interest as outcomes in this sub group have not been as low as seen in the broader general patient population. 8 8

9. Five Year Outcomes of Diabetic Patients Included into the SIRTAX Trial
Diabetes
No Diabetes
Ischemia Driven MACE, 0 to 5 YEARS
Ischemia Driven TLR, 0 to 5 YEARS
40%
40%
HR (95% Cl): 1.45 ( ), p=0.02
HR (95% Cl): 1.09 ( ), p=0.67
30%
30%
Cumulative Incidence
20%
Cumulative Incidence
20%
10%
10% 0% 0% 1 2 3 4 5 1 2 3 4 5
Years after Index PCI
Years after Index PCI
Cardiac Death or MI, 0 to 5 YEARS
ARC Definite Stent Thrombosis, 0 to 5 YEARS
40%
HR (95% Cl): 1.74 ( ), p=0.01
40%
HR (95% Cl): 1.07 ( ), p=0.85
30%
30%
Cumulative Incidence
20%
Cumulative Incidence
20%
10%
10% 0% 0% 1 2 3 4 5 1 2 3 4 5
Years after Index PCI
Years after Index PCI

10. Five Year Outcomes of Diabetic Patients Included into the SIRTAX Trial
Adjusted
HR (95% CI)
p-interaction
Cardiac death
0 to 1 year
2.67 ( )
1 to 5 years
2.16 ( )
0 to 5 years
2.28 ( )
0.72 MI
1.05 ( )
1.60 ( )
0.97
1.45 ( )
Ischemia driven TLR
1.13 ( )
1.21 ( )
0.96
1.16 ( )
MACE
1.45 ( )
0.90
1.47 ( )
1.45 ( ) .1 .2 .5 1 2 5 10
Non Diabetes
Diabetes

11. Mortality in Diabetic vs Non-Diabetic Patients in Trials With At Least 6 Months Clopidogrel
Bare Metal Stent (BMS)
Paclitaxel Eluting Stent (PES)
Sirolimus Eluting Stent (SES)
Diabetic Patients
N=3,852
Non-Diabetic Patients
N=10,947
SES vs BMS: hazard ratio 0.88 (0.55 to 1.30)
PES vs BMS: hazard ratio 0.91 (0.60 to 1.38)
SES vs PES: hazard ratio 0.95 (0.63 to 1.43)
SES vs BMS: hazard ratio 1.05 (0.69 to 1.73)
PES vs BMS: hazard ratio 0.89 (0.66 to 1.18)
SES vs PES: hazard ratio 1.23 (0.82 to 1.69)
20%
20%
16%
16%
12%
12%
Cumulative Incidence of Death Overall 8% 8% 4% 4% 0% 0% 1 2 3 4 1 2 3 4
Years after Initial Procedure
Years after Initial Procedure
No. of Events/No. of Patients
No. of Events/No. of Patients
BMS
904
37/904
15/632
7/358
10/224
2851
60/2851
26/1845
10/1052
18/811
PES
1162
35/1162
40/1020
11/535
3/158
3585
63/3585
35/3080
21/1655
12/722
SES
1078
39/1078
26/830
12/497
1/73
2857
52/2857
25/2091
10/995
6/182
Stettler C et al. Brit Med J 2008 11

12. Diabetic Patient Analysis
Methods
An analysis of outcomes in the diabetic patients fro the one randomized control trial and 4 single arm studies was prospectively planned and therefore we evaluated the effectiveness of the Resolute ZES in these patients from all these studies.
Of the 5130 patients enrolled in the RESOLUTE Global Clinical Program, a significant proportion were considered high risk with complex lesions, 1535 had diabetes and of that 57.2% that are considered “on label” diabetic patients are included in this initial analysis. The analysis of this cohort was a pre specified analysis in the Global Resolute Clinical Program. 12 12

13. RESOLUTE Global Clinical Program
Enrollment Complete - In Follow Up
RESOLUTE1
Non-RCT First-in-Human (R=139)
4 yr
RESOLUTE AC2,3
1:1 RCT vs. Xience V (R=1140; X=1152)
2 yr
RESOLUTE Int
Non-RCT Observational (R=2349)
1 yr
2.25 – 3.5mm Non-RCT vs. Hx Control (R=1242)
1 yr
RESOLUTE US4
2.25 – 3.5mm Angio/IVUS Non-RCT vs. Hx Control (R=100)
1 yr
4.0mm Angio Non-RCT vs. Hx Control (R=60)
1 yr
RESOLUTE Japan
2.5 – 3.5mm Non-RCT (R=100) vs. Hx Control
1 yr
R Japan SVS
2.25 Non-RCT vs. PG (R=63)
<1 yr
RESOLUTE US
38 mm sub-study Non-RCT vs. PG (R= )
< 30d
Enrolling / Planning
RESOLUTE Asia
Non-RCT (R≈300)
enroll
R-China Registry
Registry (R=1500 max)
enroll
R-China RCT
3:1 vs. Cypher (R=742; C=248)
plan
1 Meredith IT, et al. EuroIntervention. 2010;5: Serruys PW, et al. N Engl J Med. 2010;363:
3 Silber S, et al. Lancet. 2011;377: Yeung AC, et al. JACC. 2011;57(17):

14. RESOLUTE Global Clinical Program
Diabetic Patient Analysis
5130 Patients Enrolled
Total Diabetic Patient Population
N = 1535
‘On label’ Diabetic Population
N = 878
57.2% of total diabetic population
On label is defined as all enrolled subjects excluding subjects with bifurcation, bypass grafts, ISR, AMI ≤ 72 hours, LVEF <30%, unprotected left main lesion, >2 vessels stented, renal insufficiency or failure (creatinine ≥ 140µmol/L), total lesion length per vessel >27 mm, >1 lesion per vessel, lesion with thrombus, or total occlusion (preprocedure TIMI = 0).

15. RESOLUTE Pooled – On Label Diabetics
Baseline Characteristics
Variable, %
n=878
Age, years (Mean+SD)
65.2 ± 10.2
Men
66.4
Diabetes mellitus
100.0
Insulin Dependent DM
28.5
Hypertension
87.6
Hyperlipidemia
86.2
Current smoker
18.2
Family History
37.8
Prior percutaneous coronary intervention
34.6
Prior coronary artery bypass grafting
10.5
Prior MI
24.9
LAD
39.5
Lesion Length (mm)
22.48 ± 11.25
RVD (mm)
2.66 ± 0.48
Minimum Luminal Diameter (mm)
0.74 ± 0.39
B2/C
65.9 15 15

16. RESOLUTE Pooled – On Label Diabetics
Clinical Outcomes to 12 Months
n = 867
Percentage [%]
Death
Cardiac
Death
TV-MI
CD/TV-MI
ARC ST
Def/Prob
CI-TLR
TLF
TVF
MACE

17. RESOLUTE Pooled – On Label Diabetics
Dual Antiplatelet Therapy (DAPT) Usage
% of patients on DAPT at:
30 Days
6 Months
12 Months
Aspirin
97.7
97.1
96.8
Clopidogrel
96.3
95.6
90.6
Ticlopidine
1.9
2.0
DAPT
96.2
94.9
90.1

18. ARC Stent Thrombosis to 12 Months
RESOLUTE Pooled – On Label Diabetics
ARC Stent Thrombosis to 12 Months
% (n)
Definite ST
Early: (0 – 30 days)
0.1 (1)
Late: (31 days – 360 days)
All: (0 days – 360 days)
0.2 (2)
Probable ST
Early : (0 – 30 days)
0.0 (0)
Definite/Probable ST
0.3 (3)

19. RESOLUTE Pooled – On Label DM vs Non-DM
Target Lesion Failure (cardiac death, TV MI and TLR)
15%
Diabetics (N = 878)
P value = 0.081
Hazard Ratio = 1.341
95% CI (0.96, 1.87)
Non Diabetics (N = 1903)
10%
Cumulative Incidence of TLF
6.6% 5%
4.9% 0% 3 6 9 12
Time after Initial Procedure (months)
Error bars indicate a point-wise two-sided 95% confidence interval (±1.96*SE). Standard Error based on the Greenwood Formula.

20. RESOLUTE Pooled – On Label DM vs Non-DM
Clinically Driven Target Lesion Revascularization
15%
Diabetics (N = 878)
P value =
Hazard Ratio = 1.676
95% CI (1.03, 2.72)
Non Diabetics (N = 1903)
10%
Cumulative Incidence of TLR 5%
3.4%
2.0% 0% 3 6 9 12
Time after Initial Procedure (months)
Error bars indicate a point-wise two-sided 95% confidence interval (±1.96*SE). Standard Error based on the Greenwood Formula.

21. RESOLUTE Pooled – On Label DM vs Non-DM
Cardiac Death and Target Vessel MI
15%
Diabetics (N = 878)
P value =
Hazard Ratio = 1.134
95% CI (0.73, 1.75)
Non Diabetics (N = 1903)
10%
Cumulative Incidence of Cardiac Death/TV MI 5%
3.6%
3.1% 0% 3 6 9 12
Time after Initial Procedure (months)
Error bars indicate a point-wise two-sided 95% confidence interval (±1.96*SE). Standard Error based on the Greenwood Formula.

22. RESOLUTE Pooled – On Label DM vs Non-DM
Definite/Probable Stent Thrombosis
15%
Diabetics (N = 878)
P value =
Hazard Ratio = 1.086
95% CI (0.27, 4.34)
Non Diabetics (N = 1903)
10%
Cumulative Incidence of ARC Definite/Probable Stent Thrombosis 5%
0.3% 0%
0.3% 3 6 9 12
Time after Initial Procedure (months)
Error bars indicate a point-wise two-sided 95% confidence interval (±1.96*SE). Standard Error based on the Greenwood Formula.

23. RESOLUTE Pooled – On Label DM vs Non-DM
Patient Oriented Endpoint
Log Rank P value = 0.023
Diabetics (N = 878)
Non Diabetics (N = 1903)
20%
15%
14.4%
11.2%
Cumulative Incidence
10% 5% 0% 3 6 9 12
Time after Initial Procedure (months)
Error bars indicate a point-wise two-sided 95% confidence interval (±1.96*SE). Standard Error based on the Greenwood Formula.

24. Summary
Additional findings from the Resolute All Comers trial reinforces the lower events rates that are expected when treating “simple” patient and lesion cohorts
R-ZES and EES have similar outcomes and are safe and effective among patients with complex baseline clinical and angiographic characteristics through 1 year.
In addition the initial analysis of the diabetic patient population from larger pooled Resolute clinical program:
Indicates consistently low adverse events rates despite the higher risk nature of this patient population
Suggests that the treatment effect of the Resolute Zotarolimus eluting stent seen in the non diabetic patient population may be consistent even in the diabetic patient population