1. 3-Year Clinical Outcomes From the RESOLUTE US Study
Paul Teirstein, MD
On behalf of the RESOLUTE US Investigators
ACC.13

2. Author Disclosure
Research grants, speaker fees and consulting with Medtronic, Inc. Boston Scientific Corporation and Abbott

3. Abstract – 3-Year Follow-up of the RESOLUTE US Clinical Trial
Background: Long-term follow-up of patients treated with new generation drug-eluting stents contributes to our understanding of the risks and benefits of these devices over time. RESOLUTE US was a prospective single-arm trial designed to evaluate the effectiveness of the Resolute™ zotarolimus- eluting stent (R-ZES) in patients with de novo coronary artery disease.
Methods: Patients with lesions in vessels 2.25–4.0 mm in diameter and appropriate for one- or two-vessel treatment were enrolled. The primary endpoint at 1 year was target lesion failure (TLF); a composite of cardiac death, target vessel myocardial infarction (TVMI), and target lesion revascularization (TLR). Secondary endpoints include the components of TLF and definite/probable stent thrombosis (ST). Dual antiplatelet therapy (DAPT) was prescribed for a minimum of 6 months. Annual follow-up was obtained through 5 years.
Results: There were 1402 patients enrolled; 68.3% males and 34.4% with diabetes, including 9.6% using insulin. Most lesions were type B2/C (75%). TLF at 2 years was 7.3% including 4.3% TLR, 1.9% TVMI and 1.5% cardiac death. Overall definite/probable ST occurred in 3 (0.2%) and1 patients (0.1%) between 1 and 2 years respectively; 67.2% of patients were on DAPT at 2 years. There were 150 patients with vessels <2.25 mm and among this cohort the 2-year rate of TLF was 8.2%. Two of the 3 ST events occurred in this cohort. Among patients with diabetes the 2-year rate of TLF was 8.9% and TLR was 5.7%. There was no ST in the diabetic subgroup through 2 years.
Conclusions: Two-year follow-up demonstrates low rates of TLF in all patient cohorts with very low rates of ST following treatment of coronary artery disease with the R-ZES. Outcomes in patients with diabetes further support the safety and effectiveness of the R-ZES. Full 3-year follow-up of the RESOLUTE US trial will be presented at ACC2013.

4. RESOLUTE Global Clinical Program
Enrollment Complete – In Follow-up
RESOLUTE1
Non-RCT First-in-Human (R = 139)
5 yr
RESOLUTE AC2,3
1:1 RCT vs Xience V (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)
3 yr
RESOLUTE Japan
2.5–3.5 mm Non-RCT (R = 100) vs Hx Control
2 yr
R Japan SVS
2.25 Non-RCT vs PG (R = 65)
1 yr
RESOLUTE US
38 mm Substudy Non-RCT vs PG (R = 114)
1 yr
R-China RCT
1:1 RCT vs Taxus (R = 200; T = 200)
1 yr
RESOLUTE Asia
Non-RCT Observational (R = 312)
1 yr
R-China Registry
Non-RCT Observational (R = 1800)
1 yr
Enrolling / Planning
RI-US Registry
Post-approval Study (R ≈ 230)
Enrolling
1Meredith 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: 4

5. De Novo Native Coronary Lesion (≤35 mm lesions tx w/ 38 mm stent)
RESOLUTE US
Clinical Study Design
De Novo Native Coronary Lesion
Vessel Diameter: 2.25–4.2 mm
Lesion Length: ≤27 mm
(≤35 mm lesions tx w/ 38 mm stent)
Resolute™ stent
2.25–3.5 Clinical (n = 1242)
2.25–3.5 Angio/IVUS (n = 100)
4.0 Angio (n = 60)
38 mm Clinical (n = 110–175)
Hx Controls
Performance Goals
N = max 1577 patients
Up to 135 US sites
Clinical endpoints
30d
6mo
8mo
9mo
12mo
18mo
2yr
3yr
4yr
5yr
Angio/IVUS endpoints
Primary Endpoints:
2.25–3.5 Clinical → Target Lesion Failure at 12 mo
2.25–3.5 Angio/IVUS → In-Stent LLL at 8 mo
4.0 Angio → In-Segment LLL at 8 mo
38 mm Clinical → Target Lesion Failure at 12 mo
Drug Therapy: ASA and clopidogrel/ticlopidine ≥6 mo (per guidelines)

6. Key Inclusion Criteria Key Exclusion Criteria
RESOLUTE US
Key Eligibility Criteria
Key Inclusion Criteria
Clinical evidence of ischemic coronary disease
Single or double de novo lesion in native coronary artery
Target lesion ≤27 mm in length, diameter stenosis ≥50% <100%, and target RVD ≥2.25 mm ≤4.2 mm
Target vessel TIMI flow ≥2
Patient is able to take DAPT for at least 6 months
Treatment of up to two lesions, if the lesions are located in separate target vessels
Key Exclusion Criteria
Acute MI within 72 hours of index procedure
Previous PCI of target vessel within 9 months pre-procedure
Planned PCI of any vessel within 30 days post-procedure
Hx stroke or TIA within 6 months
LVEF <30%
Mauri L, et al. Am Heart J. 2011;161:

7. RESOLUTE US Patient Flow Chart Patients Enrolled N = 1402
1-Year Clinical Follow-up
n = 1386
98.9%
2-Year Clinical Follow-up
n = 1359
96.9%
3-Year Clinical Follow-up
n = 1341
95.6% 7 7

8. RESOLUTE US Baseline Characteristics % All Patients
(2.25 mm–4.00 mm diameter)
N = 1402 Patients / 1573 Lesions
Age, years (mean ± SD)
64.1 ± 10.7
Male
68.3
Diabetes mellitus
34.4
IDDM
9.6
Prior PCI
32.7
Reason for revascularization:
Stable angina
56.1
Unstable angina
41.9
Myocardial infarction
2.1
LAD
45.9
RVD (mm)
2.6 ± 0.5
Type B2/C lesion
75.2
Two vessel treatment
10.4
Stents per patient (mean ± SD)
1.2 ± 0.5
Stent length per patient (mm)
22.4 ± 10.5
Yeung AC, et al. J Am Coll Cardiol. 2011;57:

9. RESOLUTE US Primary Endpoint and Substudy Analyses
Primary Endpoint Analysis: Target Lesion Failure
Resolute™ ZES (2.5–3.5 mm) N = 1001
3.7%
Difference: -2.8%
Upper 1-sided 95% CI: -1.3%
Non-inferiority
P-value
<0.001
Hx Control (E-ZES) N = 1092
6.5%
Primary Non-Inferiority Met
Post-Hoc Superiority Met
Psup = 0.002
Substudy Endpoints
2.25 mm Stent Group
N = 150 patients
N = 197 lesions
TLF at 12 months cw PG: 20%
4.8%
Upper 1-sided 95% CI: 8.8%
PG: 20%
Primary Endpoint Met
P <0.001
Angiographic Cohorts
In-stent late lumen loss at 8 mos for 2.25 – 3.5 vessels cw Endeavor™ ZES
Historical control
(non-inferiority)
Resolute™ ZES
N = 100
0.39 ± 0.06
Historical Control Endeavor
0.61 ± 0.03
Difference: -0.22
Upper 1-sided 95% CI: -0.11
Non-inferiority Endpoint Met
In-segment late lumen loss at 8 mos for 4.0 vessels cw BMS
Historical control (superiority)
N = 60
0.11 ± 0.09
Historical Control Driver N = 150)
0.66 ± 0.05
Difference: Upper 1-sided 95% CI: -0.38
Superiority Endpoint Met

10. RESOLUTE US – All Patients
Target Lesion Failure to 36 Months
15%
RUS
10%
Cumulative Incidence of TLF 5% 0%
360
720
1080
Time After Initial Procedure (days)
RUS
No. at risk
1402
1384
1301
1217
% CI
1.28
4.68
7.28
8.38

11. RESOLUTE US – All Patients
Clinical Outcomes at 12 and 36 Months %
12 Months*
n = 1386
36 Months
n = 1341
Death (all)
1.3
4.7
Cardiac
0.6
2.1
MI (target vessel)
Q Wave
0.1
Non Q wave
1.2
1.9
Cardiac death + target vessel MI
3.9
ST Def/Prob (all)
0.3
Early (0-30 days)
Late ( days)
Very late (>360 days) –
TLR
2.8
4.9
TVR
4.5
9.7
TLF (cardiac death, TVMI, TLR)
4.6
8.5
TVF
6.1
12.7
* M. Leon ACC 2011.

12. RESOLUTE US – All Patients
Safety and Efficacy Outcomes at 36 Months
Resolute™ ZES (n = 1341/1402)
Events (%)
114/1341
66/1341
28/1341
28/1341
4/1341
Target lesion failure (TLF) is defined as cardiac death, target vessel MI and clinically-driven TLR.
TLR is ischemia driven.

13. Time After Initial Procedure (days)
RESOLUTE US
DAPT to 36 Months
RUS (N = 1402)
95.7
97.2
93.7
73.5
66.3
Adherence to DAPT (%)
56.9
Time After Initial Procedure (days)

14. RESOLUTE US Def/Prob Stent Thrombosis to 36 Months RUS 5% 4% 3%
Cumulative Incidence of ARC Def/Prob Stent Thrombosis 2% 1% 0%
360
720
1080
Time After Initial Procedure (days)
RUS
No. at risk
1402
1354
1292
% CI
0.00
0.14
0.22
0.30

15. RESOLUTE US – All Patients
Stent Thrombosis at 36 Months
% (n)
30 Days
n = 1399
1 Year
n = 1386
2 Years
n = 1359
3 Years
n = 1341
Stent thrombosis
(ARC def/prob)
0.1 (1)
0.1 (2)
0.2 (3)
0.3 (4)
Early (<30 days)
Late ( days)
n/a
Very late (>360 days)
30 Days - The RESOLUTE US Trial – Yeung et al. JACC Vol. 57, No. 17, 2011.
1 and 2 Year - Tolleson – SCAI 2012.

16. RESOLUTE US Main Study (2.5–3.5 mm single lesion)
Safety and Efficacy Outcomes at 36 Months
Resolute™ ZES (n = 1064/1112)
Events (%)
76/1064
43/1064
18/1064
21/1064
2/1064
Target lesion failure (TLF) is defined as cardiac death, target vessel MI and TLR (ischemia driven).
TLF rate at 2 years for Endeavor ZES was 8.1% (post-hoc analysis, Pnoninferiority < 0.001).

17. RESOLUTE US – Diabetic Patients
Safety and Efficacy Outcomes at 36 Months
Resolute™ ZES (n = 465/482)
Events (%)
50/465
31/465
14/465
7/465
0/465
Target lesion failure (TLF) is defined as cardiac death, target vessel MI and clinically-driven TLR.
TLR is ischemia driven.

18. RESOLUTE US
Conclusions
Out to 3 years, the TLF (primary endpoint) was consistently low
All patients 8.5%, main cohort ( single lesion) 7.1%
Stent thrombosis was very low (0.2%) with only 1 new ST event after 1 year
Very good outcomes in the diabetic subgroup
Low rate of TLF (10.8%) and TLR (6.7%)
No stent thrombosis out to 3 years