1. RESOLUTE All Comers Trial
A Randomized Comparison of a Zotarolimus-Eluting
Stent with an Everolimus-Eluting Stent
for Percutaneous Coronary Intervention
Primary Results
Patrick W. Serruys MD, PhD
on behalf of the Investigators
Thoraxcenter, Erasmus MC,
Rotterdam, the Netherlands
Main arena, Tuesday 25th May 2010, 16:05 – 16:17
Potential Conflicts of Interest
Speaker’s name: Patrick W. Serruys
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)
X I do not have any potential conflict of interest

2. Background
• 1st generation DES reduced rates of restenosis
• Safety concerns over very late stent thrombosis have
prompted a new 2nd generation of DES
• These 2nd generation devices utilize new stent
platforms and more biocompatible polymers
• Previous DES trials were largely performed in
on-label indications, restricting wider applicability
of their results to routine clinical practice
• Presently there are no randomized comparisons
between 2nd generation DES
RESOLUTE All Comers: Stents
Resolute DES Xience V DES
Driver BMS Multi-Link Vision BMS
Stent Platform Cobalt Alloy Cobalt Alloy
Modular Slotted Tube
Drug Zotarolimus Everolimus
Drug Density 1.6 µg/mm² 1.0 µg/mm²
Complete Drug Elution 180 days 120 days
BioLinx Fluoropolymer
– Hydrophobic C10 Polyvinylidene fluoride
Polymer System
– Hydrophilic C19
– Polyvinyl pyrrolidinone

3. RESOLUTE: Current Data
• First In Man study in 139 patients
• Angiographic outcomes:
– 4-month1 in-stent late loss: 0.12 ± 0.26 mm
– 9-month2 in-stent late loss: 0.22 ± 0.27 mm
• Clinical outcomes at 3 years3:
– MACE 11.6%, MI 5.4% and TLR 1.6%
– No definite/probable ST
1Meredith IT, et al., EuroIntervention. 2007: 3: 50-53.
2Meredith IT, et al., J Am Coll Cardiol Intv. 2009: 2:977-985.
3Ian Meredith et al., Presented at TCT. 2009.
RESOLUTE All Comers Trial Design
Any patient with symptomatic
coronary artery disease
Resolute Stent 17 European sites
Xience V Stent
n = 1150 2300 patients randomised 1:1
n = 1150
Rapid enrolment over 6 months
1:4 1:4
Angio f/u Angio f/u
n = 230 Clinical endpoints n = 230
Clinical
30d 6mo 12mo 13mo 2yr 3yr 4yr 5yr
QCA 460 (20%)
OCT 50 (2%) QCA & OCT endpoints
Primary Endpoint:
• 12-month target lesion failure (TLF), composite of cardiac death, target vessel MI
12-
12-month target
and clinically driven TLR
Secondary Endpoints:
• Clinical: Patient composite of any death, any MI, & any repeat revascularisation
revascularisation
• QCA (powered): 13-month in-stent % diameter stenosis
13-
13-month in-
in-stent
• QCA: % diameter stenosis, late loss, and binary restenosis

4. Patient Eligibility
Inclusion Criteria Exclusion Criteria
Coronary artery disease Known intolerance to
• Stable angina Aspirin, clopidogrel, heparin, cobalt
• Silent ischemia chromium, everolimus, zotarolimus,
• Acute coronary syndrome including contrast material
UA, NSTEMI and STEMI
Lesion characteristics Planned, elective surgery within
• Number of lesions : no limitation 6 months of PCI
• Number of vessels : no limitation Unless dual anti-platelet therapy
• Lesion length : no limitation could be maintained
Lesions allowed Pregnancy
ULM, CTO, bifurcation lesions,
in-stent restenosis, bypass grafts
Written informed consent Participation in another trial
Study Management
Steering Committee DSMB
P. W. Serruys (PI) J.P.G. Tijssen (Chair)
S. Silber (Co-PI) M. E. Bertrand
S. Windecker (Co-PI) U. Sigwart
Clinical Event Committee Cardialysis, Rotterdam, the Netherlands
W. Bocksch Angiographic core lab
G. Ducrocq Clinical events committee
E. McFadden Data management
C. Hanet Statistical analysis
J.P.R. Herrman
Data Monitoring
V. Legrand
Premier Research Group, Switzerland
P.W. Radke
W. Rutsch Sponsor
H.H. Tilsted Hansen Medtronic CardioVascular, Santa Rosa, CA
M. Valgimigli

5. Clinical Sites
Investigator Hospital Patients
Stephan Windecker Swiss Cardiovascular Center Bern, Switzerland 300
Patrick Serruys Erasmus University Medical Center, the Netherlands 299
Gert Richardt Segeberger Kliniken, Germany 298
Pawel Buszman American Heart of Poland, Poland 251
Henning Kelbæk The Heart Center, Denmark 233
Adrianus van Boven Leeuwarden Medical Center, the Netherlands 166
Axel Linke University Leipzig, Germany 141
Volker Klauss University of Munich, Germany 119
Sigmund Silber Kardiologische Praxis and Praxisklinik Munich, Germany 116
William Wijns O.L.V. Hospital Aalst, Belgium 76
Carlos Macaya Hospital Clinico San Carlos, Spain 58
Philippe Garot Institut Cardiovasculaire Paris-Sud, France 57
Carlo DiMario Royal Brompton Hospital, United Kingdom 55
Ganesh Manoharan Royal Victoria Hospital, United Kingdom 47
Ran Kornowski Rabin Medical Center, Israel 38
Thomas Ischinger Klinikum Bogenhausen, Germany 29
Antonio Bartorelli Centro Cardiologico Monzino, Italy 9
Clinical and Angiographic F/U
2292 patients (NL = 3366)
Enrolled and randomized
Zotarolimus-eluting stent
Zotarolimus- Randomized Everolimus-eluting stent
Everolimus-
N = 1140 pts 1:1 N = 1152 pts
Clinical F/U Clinical F/U
12 months 98.2% 12 months 97.7%
Randomized to Angio F/U Randomized to Angio F/U
N = 228 pts N = 227 pts
Angiographic F/U Angiographic F/U
13 months 62.3% 13 months 57.3%

6. Statistical Assumptions
Primary Clinical Endpoint: Target Lesion Failure at 12 Months
(Composite of cardiac death, target vessel MI and clinically driven TLR)
driven
Event rate at 12-months would be 8% and equal in both groups
12-
Non-inferiority margin of 3.5% and one-sided type I error of 0.05
Non- one-
• 2300 patients would yield >90% power to detect non-inferiority
non-
Secondary Angiographic Endpoint: In-stent Percent Diameter Stenosis at 13
In-
Months
1.5 lesions would be treated per patient
% DS at 13 months would be 16 ± 16% and equal in both groups
Non-inferiority margin of 5% and one-sided type I error of 0.05
Non- one-
Attrition rate 20%
• 460 patients would yield >90% power to detect non-inferiority
non-
Baseline Patient Characteristics
Zotarolimus stent Everolimus stent
Variable, % N = 1140 pts N = 1152 pts
Age, years (mean ± SD) 64.4 ± 10.9 64.2 ± 10.8
Men 76.7% 77.2%
Diabetes mellitus 23.5% 23.4%
Insulin treated 8.4% 7.1%
Arterial hypertension 71.1% 71.3%
Hyperlipidemia 63.9% 67.7%
Current smoker 26.5% 26.5%
Premature CAD in first degree relative 34.1% 36.7%
Prior myocardial infarction 28.9% 30.4%
Prior percutaneous coronary intervention 31.8% 32.1%
Prior coronary artery bypass grafting 10.0% 9.5%
Stable angina 33.5% 36.1%
Unstable angina 19.4% 18.9%
Acute Myocardial infarction ≤72 hours 28.9% 28.8%

7. Baseline Patient Characteristics
Zotarolimus stent Everolimus stent
Variable, % N = 1140 pts N = 1152 pts
Left ventricular ejection fraction <30% 2.8% 2.1%
Multi-vessel disease 58.4% 59.2%
Target vessel location (per patient)
Left main 2.2% 2.5%
Left anterior descending 52.6% 48.6%
Left circumflex 33.0% 32.9%
Right coronary 37.3% 41.3%
Bypass graft 2.5% 2.4%
Number of treated lesions per patient 1.5 ± 0.7 1.5 ± 0.8
SYNTAX score 15 ± 9 15 ± 9
≥1 small vessel (RVD ≤2.75 mm) 67.8% 67.4%
≥1 lesion length >18 mm 18.2% 21.2%
≥1 bifurcation/trifurcation 16.9% 17.7%
≥1 total occlusion 16.3% 17.2%
≥1 In-stent restenosis 8.1% 8.0%
Off-label use 67.0% 65.6%
Procedural Characteristics
Zotarolimus stent Everolimus stent
N = 1140 pts, N = 1152 pts,
1661 lesions 1705 lesions P
No. of stents per patient 1.9 ± 1.2 2.0 ± 1.3 0.02
Stent length per patient (mm) 34.4 ± 24.5 37.0 ± 26.5 0.02
Pre-stent balloon dilatation 69.5% 70.2% NS
Implantation of study stent only 98.0% 96.9% NS
Lesion success 98.9% 99.1% NS
Device success 97.0% 96.6% NS
Procedure success 94.6% 94.2% NS

8. 1º Endpoint: Target Lesion Failure
(Cardiac death, target vessel MI, and clinically driven TLR) at 1 year
20
ZES (N = 1140) Log-Rank P = 0.92
Cumulative incidence of events [%]
EES (N = 1152)
15
ZES 8.2% vs. EES 8.3%
Pnon-inferiority <0.001
non-
non-inferiority
10 8.3%
8.2%
5
0
0 180 360
Time after initial procedure [days]
No. at risk 0 30 60 90 120 150 180 210 240 270 300 330 360
ZES 1140 1110 Primary Non-Inferiority 1058 1051 1042 1038
10841076 Non- 1062 1060 Endpoint Met
Non-Inferiority 1061 1047 1046 1038
1070 1037 1025
EES 1152 1123 10881080 1078 1074 1068 1032 1019
Error bars indicate a point-wise two-sided 95% confidence interval (±1.96*SE)
Standard Error based on the Greenwood Formula
1º Endpoint Analysis: TLF
(Cardiac death, target vessel MI, and clinically driven TLR) at 1 year
ZES EES Non-inferiority
Non-
(N = 1140) (N = 1152)
Difference : -0.1% P value
8.2% 8.3% Upper 1-sided 95% CI : 1.8%
1- <0.001
Zone of non-inferiority
Pre-specified margin = 3.5%
Non-inferior
-1.0 -0.5 0.0 0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0 %
Upper one-sided 95% CI
Primary Non-Inferiority Endpoint Met
Non-

9. 1º Endpoint Components: TLF
(Cardiac death, target vessel MI, and clinically driven TLR) at 1 year
Cardiac Death (%) TVMI (%) ID-TLR (%)
P = 0.61 P = 0.92 P = 0.50
4.2 4.1 3.9
3.4
1.7
1.3
ZES EES ZES EES ZES EES
n = 1119 n = 1126 n = 1119 n = 1126 n = 1119 n = 1126
1º Endpoint TLF to 1 Year
Odds Ratio Odds Ratio P value
Pre-Specified Subgroups [95% CI] [95% CI]
All Patients (N = 2292) 0.98 [0.73, 1.33] 0.94
Off-Label (n = 1520) 0.91 [0.64, 1.29] 0.66
Small Vessels ≤2.75 mm (n = 1308) 1.01 [0.69, 1.48] 1.00
Acute MI <72 hr (n = 662) 1.36 [0.73, 2.57] 0.34
Multivessel Treatment (n = 570) 0.85 [0.50, 1.47] 0.58
Diabetes (n = 538) 1.45 [0.82, 2.58] 0.25
Overlapping Stents (n = 411) 1.06 [0.55, 2.05] 0.87
Bifurcations (n = 392) 0.99 [0.52, 1.87] 1.00
Long Lesions >18 mm (n = 381) 0.86 [0.44, 1.67] 0.74
In-Stent Restenosis (n = 182) 0.61 [0.24, 1.57] 0.35
Renal Insufficiency (n = 80) 0.91 [0.28, 3.02] 1.00
Bypass Graft (n = 56) 1.25 [0.30, 5.26] 1.00
Left Main (n = 54) 1.65 [0.33, 8.21] 0.69
0.1 1 10
Favors Favors
ZES EES

10. Composite Clinical Endpoints
RESOLUTE All Comers at 1 year
TLF (%) TVF (%) MACE (%) Patient Composite (%)
(CD, TV MI, CI-TLR) (CD, TV MI, TVR) (D, MI, eCABG, TLR) (D, All MI, All Revasc)
P = 0.94 P = 0.42 P = 0.66 P = 1.00
9.6 9.7 9.6
9.0 8.7 9.0
8.2 8.3
Resolute Xience Resolute Xience Resolute Xience Resolute Xience
n = 1119 n = 1126 n = 1119 n = 1126 n = 1119 n = 1126 n = 1119 n = 1126
ARC Stent Thrombosis to 1 year
Zotarolimus stent Everolimus stent
% (n) n = 1119 n = 1126 P
Definite ST
Acute: (0 – 1 day) 0.4% (4) 0.1% (1) NS
Sub-Acute: (2 – 30 days) 0.4% (5)*† 0.0% (0) 0.03
Late: (31 days – 360 days) 0.4% (5)* 0.2% (2) NS
All: (0 days – 360 days) 1.2% (13) 0.3% (3) 0.01
Definite/Probable ST
Acute: (0 – 1 day) 0.4% (5)† 0.2% (2) NS
Sub-Acute: (2 – 30 days) 0.7% (8)*† 0.4% (4) NS
Late: (31 days – 360 days) 0.6% (7)* 0.2% (2) NS
All: (0 days – 360 days) 1.6% (18) 0.7% (8) NS
*One patient had a definite ST at day 4 and 31
†One patient had a probable ST on day 0 and a definite ST on day 5

11. Stent Thrombosis and CD/MI
ARC Definite/Probable ST Cardiac Death and
10 10 Target Vessel MI
Cumulative incidence of events [%]
Cumulative incidence of events [%]
ZES ZES
EES EES
Log Rank P = 0.05 Log Rank P = 0.96
5 5
0 0
0 180 360 0 180 360
Time after initial procedure [days] Time after initial procedure [days]
Small, early difference in stent thrombosis
did not translate into differences in cardiac death or TVMI
Error bars indicate a point-wise two-sided 95% confidence interval (±1.96*SE)
Standard Error based on the Greenwood Formula
2º QCA Endpoint Analysis:
In-stent Percent Diameter Stenosis at 13 Months
ZES EES
(Lesions = 191) (Lesions = 186) Non-inferiority
Non-
Difference* : 2.03 P value*
21.7 ± 19.8 ± Upper 1-sided 95% CI* : 4.73
1- 0.035
14.4 14.6
Zone of non-inferiority
Pre-specified margin = 5.0
Non-inferior
0.0 1.0 2.0 3.0 4.0 5.0 6.0
Upper one-sided 95% CI
Powered Secondary Non-Inferiority Endpoint Met
Non-
*Calculated using least square means

12. In stent late loss at 13 Months
ZES (n = 183 lesions) EES (n = 177 lesions)
100
90
80
70
% of Lesions
60
50
40
30
0.27 ± 0.43 vs. 0.19 ± 0.40
20 (P = 0.08)
10
0
-1 0 1 2 3
In-stent Late Loss (mm)
Complex Patient Subgroup
Professor Stephan Windecker
PCR Symposium

13. RESOLUTE All Comers
“Complex” or “Off-Label” Definition:
• Bifurcation
• SVG
• 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)
Patient Complexity
All
34%
66%
Resolute
Resolute Xience V
Xience V
33% Simple Complex 34%
67% 66%
P = 0.51

14. Complex Patients: Target Lesion Failure
(a composite of cardiac death, target vessel MI, and clinically driven TLR)
N = 698 patients
20
Resolute (ZES) P = 0.59
Cumulative incidence of events [%]
Xience V (EES)
15
10 9.8%
8.9%
5
0
0 180 360
Time after initial procedure [days]
Complex Patients: TLF Components
RESOLUTE All Comers at 1 year
Resolute (n= 764)
Xience V (n=756)
P = 0.80 P = 0.24 P = 0.90
%
4.4 4.3 4.4
4.0
2.2
1.3
TLR Cardiac Death MI

15. Complex Patients: Composite Endpoints
RESOLUTE All Comers at 1 year
TLF (%) TVF (%) MACE (%)
(CD, TV MI, CI-TLR) (CD, TV MI, TVR) (D, MI, eCABG, TLR)
P = 0.67 P = 0.45 P = 0.15
11.1 11.5
9.7 9.8
8.9 9.2
Resolute Xience V Resolute Xience V Resolute Xience V
n = 764 n = 756 n = 756 n = 764 n = 764 n = 756
Conclusion
• Both the Resolute zotarolimus-eluting stent and the
Xience V everolimus-eluting stent were associated
with a relatively low frequency of adverse events
even in this complex, all-comers patient population
• The new generation Resolute zotarolimus-eluting
stent was found to be as safe and effective as the
Xience V everolimus-eluting stent in this
predominantly off-label population