Transcript RESOLUTE US

2 Year Clinical Outcomes from
the Pivotal RESOLUTE US Study
Laura Mauri MD, MSc
on behalf of the RESOLUTE US
Investigators
Brigham and Women’s Hospital
Boston, MA
ACC 2012
RESOLUTE Global Clinical Program
Enrollment Complete - In Follow Up
RESOLUTE1
Non-RCT First-in-Human (R=139)
5 yr
1:1 RCT vs. Xience V (R=1140; X=1152)
2 yr
RESOLUTE Int4
Non-RCT Observational (R=2349)
2 yr
RESOLUTE US5
2.25 – 4.0 mm Non-RCT vs. Hx Control (R=1402)
2 yr
2.5 – 3.5 mm Non-RCT (R=100) vs. Hx Control
2 yr
RESOLUTE AC2,3
RESOLUTE Japan
R Japan SVS
2.25 Non-RCT vs. PG (R=65)
< 1yr
38 mm sub-study Non-RCT vs. PG (R=114)
< 1yr
1:1 RCT vs. Taxus (R=200; T=200)
< 1yr
RESOLUTE Asia
Non-RCT Observational (R=312)
< 1yr
R-China Registry
Non-RCT Observational (R=1800)
< 1yr
Post-approval study (R=230)
plan
RESOLUTE US
R-China RCT
Enrolling / Planning
RI-US Registry
1 Meredith
IT, et al. EuroIntervention. 2010;5:692-7. 2 Serruys PW, et al. N Engl J Med. 2010;363:136-46. 3 Silber S, et al. Lancet.
2011;377:1241-47. 4 Neumann FJ, et al. EuroIntervention. 2012;7(10):1181-8. 5 Yeung AC, et al. JACC. 2011;57:1778-83.
RESOLUTE US
Clinical Study Design
PI: M. Leon, L. Mauri, A. Yeung
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)
38mm 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
Angio/IVUS endpoints
Primary Endpoints:
•
•
•
•
2.25–3.5 Clinical → Target Lesion Failure at 12mo
2.25–3.5 Angio/IVUS → In-Stent LLL at 8mo
4.0 Angio → In-Segment LLL at 8mo
38 mm Clinical → Target Lesion Failure at 12mo
Drug Therapy: ASA and clopidogrel/ticlopidine ≥ 6mo (per guidelines)
Mauri L, et al. Am Heart J. 2011;161:807-14.
3yr
4yr
5yr
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 ≤27mm in length,
diameter stenosis ≥50% <100%, and
target RVD ≥2.25mm ≤4.2mm
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
Mauri L, et al. Am Heart J. 2011;161:807-14.
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%
RESOLUTE US
Patient Flow Chart
Patients Enrolled
N = 1402
1Yr Clinical Follow-up
n = 1386
98.9%
2Yr Clinical Follow-up
n = 1359
96.9%
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
RVD (mm)
45.9
2.6 ± 0.5
Type B2/C lesion
75.2
Two vessel treatment
10.4
Stents per patient (mean ± SD)
Stent length per patient (mm)
Yeung AC, et al. J Am Coll Cardiol. 2011;57:1778-83.
1.2 ± 0.5
22.4 ± 10.5
RESOLUTE US – All Patients
Target Lesion Failure to 24 Months
25
Cumulative Incidence of TLF (%)
RESOLUTE US (N=1402)
RESOLUTE All Comers (N=1140)
20
RESOLUTE International (N=2349)
15
11.2%
9.8%
10
7.3%
5
0
0
90
180
270
360
450
Time After Initial Procedure (Days)
Error bars indicate a point-wise two-sided 95% confidence interval (±1.96*SE).
Standard Error based on the Greenwood Formula.
540
630
720
RESOLUTE US – All Patients
Safety and Efficacy Outcomes at 24 Months
Events [%]
Resolute ZES (n=1359/1402)
99/1359
58/1359
20/1359
26/1359
3/1359
TLF
TLR
Cardiac
Death
TV-MI
ST
(ARC Def/Prob)
Target lesion failure (TLF) is defined as cardiac death, target vessel MI and TLR.
TLR is ischemia driven.
RESOLUTE US – All Patients
Clinical Outcomes at 12 and 24 Months
12M
24M
n = 1386
n = 1359
1.3
3.0
Cardiac
0.6
1.5
MI (target vessel)
1.3
1.9
Q Wave
0.1
0.1
Non Q wave
1.2
1.8
Cardiac death + target vessel MI
1.9
3.2
ST Def/Prob (all)
0.1
0.2
Early (0-30 days)
0.1
0.1
Late (31-360 days)
0.1
0.1
--
0.1
TLR
2.8
4.3
TVR
4.5
7.6
TLF (cardiac death, TV-MI, TLR)
4.6
7.3
TVF
6.1
10.1
%
Death (all)
Very late (>360 days)
DAPT to 24 Months
Adherence to DAPT (%)
RESOLUTE US, All Comers, International Trials
100
97.3
97.1
95.8
95.5
90
93.8
93.1
80
R-US (N=1402)
R-INT (N=2349)
R-AC (N=1140)
91.1
93.5
84.1
73.8
70
67.2%
60
50
43.9%
40
30
20
18.6%
10
0
30
180
360
Time After Initial Procedure (days)
540
720
Def/prob Stent Thrombosis to 24 Months
RESOLUTE US, All Comers, International Trials
25
RESOLUTE US (N=1402)
RESOLUTE All Comers (N=1140)
20
RESOLUTE International (N=2349)
15
10
5
0
0
90
180
270
360
450
540
Time After Initial Procedure (days)
Error bars indicate a point-wise two-sided 95% confidence interval (±1.96*SE).
Standard Error based on the Greenwood Formula.
630
1.9%
1.0%
0.2%
720
RESOLUTE US – All Patients
Stent Thrombosis at 24 Months
30 Days
n=1399
1 Year
n=1386
2 Year
n=1359
0.1 (1)
0.1 (2)
0.2 (3)
0.1 (1)
0.1 (1)
0.1 (1)
Late (30-360 days)
n/a
0.1 (1)
0.1 (1)
Very Late (>360 days)
n/a
n/a
0.1 (1)
% (n)
Stent thrombosis
(ARC def/prob)
Early (< 30 days)
RESOLUTE US Main Study (2.5-3.5mm single lesion)
Safety and Efficacy Outcomes at 24 Months
Events [%]
Resolute ZES (n=968/1001)
57/968
TLF
10/968
Cardiac
Death
17/968
33/968
1/968
TV-MI
TLR
ST
(ARC Def/Prob)
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)
RESOLUTE US – 2.25mm Cohort
Safety and Efficacy Outcomes at 24 Months
Events [%]
Resolute ZES (n=147/150)
12/147
TLF
5/147
Cardiac
Death
2/147
TV-MI
Target lesion failure (TLF) is defined as cardiac death, target vessel MI and TLR.
TLR is ischemia driven.
7/147
TLR
2/147
ST
(ARC Def/Prob)
RESOLUTE US – Diabetic Patients
Safety and Efficacy Outcomes at 24 Months
Events [%]
Resolute ZES (n=474/482)
42/474
TLF
10/474
Cardiac
Death
7/474
27/474
0/474
TV-MI
TLR
ST
(ARC Def/Prob)
Target lesion failure (TLF) is defined as cardiac death, target vessel MI and TLR.
TLR is ischemia driven.
RESOLUTE US – Diabetic Patients
Safety and Efficacy Outcomes at 24 Months
Diabetic (n=474/482)
Events [%]
Non-Diabetic (n=885/920)
42/474
57/885
TLF
10/474
10/885
Cardiac
Death
7/474
19/885
TV-MI
Target lesion failure (TLF) is defined as cardiac death, target vessel MI and TLR.
TLR is ischemia driven.
27/474 31/885
TLR
0/474
3/885
ST
(ARC Def/Prob)
RESOLUTE US
Conclusions
• Out to 2 years, the TLF (primary endpoint) was
consistently low in all groups studied
– All patients 7.3%, main cohort (2.5-3.5 single
lesion) 5.9%, small vessels (2.25 mm) 8.2%
• Stent thrombosis was very low (0.2%) with only
1 new ST event after 1 year, indicating a
favorable safety profile
• Very good outcomes in the diabetic subgroup
– Low rate of TLF (8.9%) and TLR (5.7%)
– No stent thrombosis out to 2 years