1. The Resolute Zotarolimus-eluting Stent in Patients with Diabetes Mellitus: One Year Outcomes
Prof. Dr. Sigmund Silber, FESC, FACC
On behalf of the RESOLUTE
Clinical Program Investigators
TCT 2011

2. Background Diabetics have significantly higher event rates because of:
Endothelial dysfunction
Impaired platelet function
Altered coagulation / fibrinolysis
Increased smooth muscle cell proliferation

3. *In the absence of new Q waves
Percutaneous Coronary Intervention Multivariate Correlates of Cumulative Late Mortality
7,106 patients discharged alive post-PCI, followed years
Hazard Ratio ± 95% CI (p<0.05)
Renal Impairment
Diabetes mellitus
CK elevation (8xULN)*
Saphenous vein graft
Prior MI
Unstable angina
Left main PCI
Elevated cholesterol
Current smoker
Advanced age
*In the absence of new Q waves
Stone G. et al, Circulation 2001;104:642-7 3 3

4. Stone G. et al, Circulation 2011; 124:893-900
Clinical Outcomes In Patients With vs. Without Diabetes Mellitus
Stone G. et al, Circulation 2011; 124:

5. RESOLUTE Pooled Diabetics
Background:
Resolute ZES was equivalent to Xience V EES in the RESOLUTE All Comers trial.
Purpose:
Patient level data of 5 Resolute clinical trials were pooled together to evaluate the clinical outcomes of patients with diabetes mellitus and compared to Xience V EES.

6. RESOLUTE Global Clinical Program
Pooled Analysis of Diabetic Patients
Trial
R-ZES
(N)
Patient type
Diabetes
(%)
Diabetes (N)
RESOLUTE
139
Protocol defined 17 24
RESOLUTE All Comers
1140
All Comers
268
RESOLUTE International
2349 30
716
RESOLUTE US
1402 34
482
RESOLUTE Japan
100 45
Pooled Program
5130
1535
Protocol defined: inclusion criteria limited the inclusion of specific lesion and vessel characteristics.

7. RESOLUTE Pooled Patient Level Analysis
Baseline Characteristics %
R-ZES
Non-Diabetics
N = 3595
Diabetics
N = 1535 P
Age (yr)
63.1 ± 11.2
65.6 ± 10.2
<0.001
Male
77.8
68.1
IDDM --
29.6
Hypertension
67.8
86.3
Hyperlipidemia
67.7
80.5
Current smoker
26.0
18.2
Family history
38.1
35.1
0.07
Prior MI
25.9
27.6
0.21
Prior PCI
29.3
34.5
Prior CABG
7.4
11.2
Cardiac status:
Stable angina
38.0
39.7
Unstable angina
25.5
26.8
Myocardial infarction
24.3
18.1

8. RESOLUTE Pooled Patient Level Analysis
Lesion Characteristics %
R-ZES
Non-Diabetics
N = 3595
Diabetics
N = 1535 P
LAD
50.5
46.8
0.02
RVD (mm)
2.8 ± 0.5
2.7 ± 0.5
<0.001
MLD (mm)
0.7 ± 0.4
0.7 ± 0.5
0.73
Diameter stenosis
75.7 ± 16.6
75.1 ± 15.9
0.21
Lesion length (mm)
15.8 ± 9.4
15.7 ± 9.5
0.67
Lesions per patient
1.3 ± 0.6
0.60
Stents per patient
1.5 ± 1.0
1.5 ± 0.9
0.34
Stent length per patient
29.2 ± 19.8
28.5 ± 18.8
0.23
Direct stenting
27.1
23.0

9. RESOLUTE Pooled Diabetics
Methods
Pooled individual patient level analysis
1535 Resolute (R-ZES) patients from 1 RCT (R-AC, 100% monitoring), 3 single arm studies (100% monitoring) and one observational study (25% monitoring)
Propensity adjustments on comparative statistics were made to compare with Xience V EES (N = 1152) from the RESOLUTE All Comers (R-AC) trial
Propensity scores calculated from 31 patient characteristics were used to adjust p-values, hazard ratio’s and 95% CI
Cumulative incidences at 12 months were calculated
Strengths: Prospective trials, consistent inclusion definitions across studies, propensity adjustment, completeness of follow-up
Limitations: Observational design

10. RESOLUTE Pooled Patient Level Analysis
1° Endpoint: Target Lesion Failure (cardiac death, TVMI, TLR)
Non-Diabetics
(N=4477)
Diabetics
(N=1805) 10
R-ZES 10
R-ZES
9.0%
EES
EES
8.3%
7.8%
6.1% 5 5
Cumulative Incidence of TLF (%)
Adjusted P = 0.09
HR (95% CI)=
0.77 (0.57, 1.04)
Adjusted P = 0.96
HR (95% CI)=
1.01 (0.62, 1.64) 3 6 9 12 3 6 9 12
Time After Procedure (months)
Time After Procedure (months)
R-ZES
EES
3595
3539
3439
3389
3335
882
855
820
808
796
1535
1518
1470
1440
1408
270
266
257
253
244

11. RESOLUTE Pooled Patient Level Analysis
Target Lesion Revascularization
Non-Diabetics
(N=4477)
Diabetics
(N=1805) 10
R-ZES 10
R-ZES
EES
EES
Adjusted P = 0.63
HR (95% CI)=
1.12 (0.70, 1.80)
Adjusted P = 0.89
HR (95% CI)=
1.05 (0.54, 2.02) 5 5
5.0%
Cumulative Incidence of TLR (%)
4.0%
3.0%
2.9% 3 6 9 12 3 6 9 12
Time After Procedure (months)
Time After Procedure (months)
R-ZES
EES
3595
3589
3521
3470
3420
882
878
856
844
832
1535
1532
1495
1467
1436
270
261
256
247

12. RESOLUTE Pooled Patient Level Analysis
Cardiac Death and Target Vessel MI
Non-Diabetics
(N=4477)
Diabetics
(N=1805) 10
R-ZES 10
R-ZES
EES
EES
Adjusted P = 0.02
HR (95% CI)=
0.64 (0.44, 0.93)
Adjusted P = 0.73
HR (95% CI)=
1.12 (0.59, 2.14)
5.7%
Cumulative Incidence of
Cardiac Death/TVMI (%) 5 5
4.9%
4.7%
3.6% 3 6 9 12 3 6 9 12
Time After Procedure (months)
Time After Procedure (months)
R-ZES
EES
3595
3542
3459
3432
3399
882
855
828
824
816
1535
1520
1479
1457
1444
270
266
260
258
254

13. RESOLUTE Pooled Patient Level Analysis
ARC Def/Prob Stent Thrombosis
Non-Diabetics
(N=4477)
Diabetics
(N=1805) 10
R-ZES 10
R-ZES
EES
EES
Adjusted P = 0.42
HR (95% CI)=
1.48 (0.57, 3.83)
Adjusted P = 0.41
HR (95% CI)=
1.93 (0.41, 9.15)
Cumulative Incidence of
ARC Def/Prob ST (%) 5 5
1.0%
0.7%
0.8%
0.7% 3 6 9 12 3 6 9 12
Time After Procedure (months)
Time After Procedure (months)
R-ZES
EES
3595
3590
3537
3513
3485
882
879
864
860
853
1535
1532
1503
1484
1472
270
263
261
257

14. RESOLUTE Pooled Patient Level Analysis
Resolute ZES in Non-DM (N=3595), NIDDM (N=1080) and IDDM (N=455)
Clinically driven
TLR (%)
Cardiac Death /
TV-MI (%)
ARC Def/Prob
ST (%)
p = 0.84
p = 0.76
p = 0.81
Events (%)
Non-DM
NIDDM
Non-DM
NIDDM
Non-DM
NIDDM
Reported event rates are cumulative incidence endpoints, P-values are adjusted with propensity score quintiles.

15. RESOLUTE Pooled Patient Level Analysis
Resolute ZES in Non-DM (N=3595), NIDDM (N=1080) and IDDM (N=455)
Clinically driven
TLR (%)
Cardiac Death /
TV-MI (%)
ARC Def/Prob
ST (%)
p < 0.001
p = 0.003
p = 0.02
p = 0.84
p = 0.76
p = 0.81
Events (%)
Non-DM
NIDDM
IDDM
Non-DM
NIDDM
IDDM
Non-DM
NIDDM
IDDM
Reported event rates are cumulative incidence endpoints, P-values are adjusted with propensity score quintiles.

16. RESOLUTE Pooled Patient Level Analysis
Conclusions
From this analysis of diabetic patients enrolled in the RESOLUTE Global Clinical Program, we conclude:
In patients with diabetes mellitus, there seems to be no difference in outcomes between Resolute ZES and Xience EES at 1 year.
The data indicate consistent low adverse events rates (4.0% TLR, 1.0% ST) with Resolute ZES despite the higher risk nature of this patient population.
Despite the presence of non-insulin dependent diabetes, clinical outcomes with the Resolute ZES remained low and consistent with the outcomes seen with the non-diabetic patient population.
Although good results observed in patients with insulin dependent diabetes mellitus, there remains room for improvement in patient care for this challenging patient group.