Transcript RESOLUTE Global Clinical Program

Five-Year Follow-up of Safety and Efficacy of the
Resolute Zotarolimus-Eluting Stent: Insights
from the RESOLUTE Global Clinical Trial Program
in Approximately 8000 Patients
Prof. Sigmund Silber, MD, PhD
FESC, FACC, FAHA
Cardiology Practice and Heart Center at the Isar, Munich, Germany
on behalf of the RESOLUTE Global Clinical Program Investigators
euroPCR 2015
Potential conflicts of interest
Speaker's name: Sigmund Silber
 Research Grant from Medtronic for the RESOLUTE All Comers
Randomized Trial
RESOLUTE Pooled – 5 Years
Background
• Individual trials, while powered for composite endpoints of
various parameters, are often underpowered to show real and
truly evidence based differences for low-frequency but
important adverse clinical events such as stent thrombosis.
• Objective of the current analysis is to assess the long-term
safety and efficacy outcomes of the Resolute™ zotarolimuseluting stent (R-ZES) in nearly 8000 patients enrolled in the
RESOLUTE Global Clinical Trial Program.
RESOLUTE Pooled – 5 Years
Methods
• This pooled analysis includes all trials within the RESOLUTE Global
Clinical Program, including regulatory trials with 100% monitoring,
all with high rates of follow-up.
• Patient level data of all 7618 Resolute patients were pooled,
including data to the latest available follow-up of each trial.
• Kaplan Meier cumulative incidence out to 5 year follow-up was
calculated.
• Strengths: All trials were prospectively performed and event
definitions across studies were consistent. The independent clinical
event adjudication was harmonized across all studies.
• Limitations: post-hoc analysis
The RESOLUTE Global Clinical Program:
7618 Patients Included in this Pooled Analysis
RESOLUTE1
Available
follow-up
Non-RCT First-in-Human (R=139)
5 yr
RESOLUTE AC2,3
1:1 RCT vs. Xience V™ EES (R=1140; X=1152)
5 yr
RESOLUTE Int4,5
Non-RCT Observational (R=2349)
3 yr
2.25 – 4.0 mm Non-RCT vs. Hx Control (R=1402)
5 yr
2.5 – 3.5 mm Non-RCT (R=100) vs. Hx Control
5 yr
2.25 Non-RCT vs. PG (R=65)
3 yr
38 mm sub-study Non-RCT vs. PG (R=114)
3 yr
Non-RCT Observational (R=312)
2 yr
1:1 RCT vs. Taxus™ PES (R=200; T=200)
3 yr
Non-RCT Observational (R=1800)
2 yr
RESOLUTE US6
RESOLUTE Japan
R-Japan SVS
RESOLUTE US7
RESOLUTE Asia7
R-China RCT8
R-China Registry9
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.
FJ, et al. EuroIntervention. 2012;7(10):1181-8. 5 Belardi JA, et al. J Interv Cardiol. 2013;26(5):515-23. 6 Yeung AC, et al. JACC. 2011;57:1778-83.
7 Lee M, et al. Am J Cardiol. 2013;112(9):1335-41. 8 Xu B, et al. JACC Cardiovasc Interv. 2013;6(7):664-70. 9 Qiao S, et al. Am J Cardiol. 2014;113(4):613-20.
4 Neumann
RESOLUTE Pooled – 5 Years
Baseline Patient Characteristics
%
N = 7618 Pts
Age (yr)
63.0 ± 11.0
Male
75.4
Diabetes mellitus
30.4
IDDM
6.7
Hypertension
71.0
Hyperlipidemia
62.3
Current smoker
26.4
Family history
29.1
Prior MI
29.2
Prior PCI
25.8
Prior CABG
6.3
Cardiac Status:
Stable angina
33.0
Unstable angina
38.1
All myocardial infarction
25.9
Acute coronary syndrome
52.4
RESOLUTE Pooled – 5 Years
Lesion and Procedure Characteristics
%
N = 7618 Pts,
10186 Lesions
LAD
53.2
LCx
29.0
RCA
34.4
Left Main
1.8
Bypass graft
1.1
B2/C lesion
67.5
Reference Vessel Diameter (mm)
2.8 ± 0.5
Minimum Lumen Diameter (mm)
0.6 ± 0.5
Percent Diameter Stenosis
77.5 ± 16.2
Lesion length (mm)
18.2 ± 11.3
No. of lesions treated per patient
1.3 ± 0.6
No. of stents per patient
1.6 ± 1.0
Total stent length per patient (mm)
33.10 ± 22.59
Multi-vessel treament (%)
20.5
Complex patient1
46.7
1Complex patient
definition: bifurcation, bypass grafts, 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 total occlusion (preprocedure TIMI = 0).
RESOLUTE Pooled – 5 Years
Definition of Composite Endpoints
Device Oriented
Composite Endpoint
Patient Oriented
Composite Endpoint
Target Lesion Failure (TLF)
(POCE)
Cardiac Death
All Deaths
Target Vessel Myocardial Infarction (TV-MI)
All Myocardial Infarctions
Target Lesion Revascularization
(clinically indicated, TLR)
All Revascularizations
Cutlip DE, et al. Circulation. 2007; 115: 2344-2351
RESOLUTE Pooled – 5 Years
Individual Components of the
Device-Oriented Endpoint
Cumulative Incidence (%)
30
Cardiac Death
25
20
15
10
5.0
5
0
0
1
2
3
4
5
4542
4.0%
2465
5.0%
Time After Initial Procedure (years)
Cardiac Death
7618
0.0%
7616
1.0%
7375
1.9%
6714
2.8%
RESOLUTE Pooled – 5 Years
Individual Components of the
Device-Oriented Endpoint
Cumulative Incidence (%)
30
Cardiac Death
Target Vessel MI (TV-MI)
25
20
15
10
5.0
4.4
5
0
0
1
2
3
4
5
4542
4.0%
4386
3.9%
2465
5.0%
2377
4.4%
Time After Initial Procedure (years)
Cardiac Death
TV-MI
7618
0.0%
7618
1.0%
7616
1.0%
7538
2.8%
7375
1.9%
7179
3.2%
6714
2.8%
6506
3.6%
RESOLUTE Pooled – 5 Years
Individual Components of the
Device-Oriented Endpoint
Cumulative Incidence (%)
30
Cardiac Death
Target Vessel MI (TV-MI)
Target Lesion Revascularization (TLR)
25
20
15
10
6.3
5.0
4.4
5
0
0
1
2
3
4
5
Time After Initial Procedure (years)
Cardiac Death
TV-MI
TLR
7618
0.0%
7618
1.0%
7618
7616
1.0%
7538
2.8%
7608
7375
1.9%
7179
3.2%
7191
6714
2.8%
6506
3.6%
6444
4542
4.0%
4386
3.9%
4318
2465
5.0%
2377
4.4%
2327
0.1%
2.6%
4.0%
4.5%
5.1%
6.3%
RESOLUTE Pooled – 5 Years
Device Oriented = Target Lesion Failure (TLF)
Cumulative Incidence (%)
50
Device-Oriented Endpoint (TLF): Cardiac Death, TV-MI, TLR
40
30
20
13.4
10
5.7
0
0
1
2
3
4
5
4196
11.4%
2257
13.4%
Time After Initial Procedure (years)
TLF
7618
1.1%
7532
5.7%
7027
8.1%
6280
9.5%
RESOLUTE Pooled – 5 Years
Device- vs. Patient-Oriented Endpoint
Cumulative Incidence (%)
50
Device-Oriented Endpoint (TLF): Cardiac Death, TV-MI, TLR
Patient-Oriented Endpoint (POCE): All Deaths, All MI, All Revascularizations
40
30
29.5
20
13.4
11.2
5.7
10
0
0
1
2
3
4
5
4196
3746
2257
1926
Time After Initial Procedure (years)
TLF
POCE
7618
7618
7532
7530
7027
6661
6280
5801
Note for reference: POCE in RESOLUTE All-Comers was not statistically significant between Resolute ZES and Xience V EES.
RESOLUTE Pooled – 5 Years
DAPT Usage - overall
R-Pooled
(N=7618)
Patients Receiving DAPT (%)
100
91.0 %
75
47.3%
50
37.0%
34.4%
31.9%
25
0
1
6
12
24
36
Time After Initial Procedure (months)
48
60
RESOLUTE Pooled – 5 Years
DAPT Usage - Individual Trials
R-Pooled
(N=7618)
RESOLUTE FIM (N=139)
R-All Comers (N=1140)
R-International (N=2349)
R-US (N=1402)
R-Japan (N=100)
R-Japan SVS (N=65)
R-38mm (N=223)
R-Asia Dual vessel (N=202)
R-China RCT (N=200)
R-China Registry (N=1800)
100
Patients Receiving DAPT (%)
90
80
75
70
66.1% (Japan)
65.6% (Asia + US)
60
65.8%
(Asia)
50
51.0% (China)
46.6% (US)
39.4% (ANZ)
40
34.6% (Intern.)
30
25
20
20.1% (China)
10
0
1
6
12
24
62.5%
(Japan)
36
Time After Initial Procedure (months)
48
31.9%
11.0%
(Europe +
Israel)
60
RESOLUTE Pooled – 5 Years
Definite Stent Thrombosis (ARC)
Cumulative Incidence of
ARC Definite ST (%)
5
4
3
2
1
0.46
0.78
0
0
1
2
3
4
5
Time After Initial Procedure (years)
No. at risk
7618
7611
7347
6680
4516
2450
% CI
0.07
0.46
0.56
0.62
0.66
0.78
Cumulative Incidence of
ARC Definite/Probable ST (%)
RESOLUTE Pooled – 5 Years
Definite/Probable Stent Thrombosis
5
4
3
2
1.20
0.67
1
0
0
1
2
3
4
5
Time After Initial Procedure (years)
No. at risk
7618
7610
7344
6676
4511
2443
% CI
0.08
0.67
0.84
0.95
1.07
1.20
Cumulative Incidence of ARC
Very Late Definite/Probable ST (%)
RESOLUTE Pooled – 5 Years
Very Late Stent Thrombosis (Definite / Probable)
5
4
3
2
1
0.54
0
1
2
3
4
5
Time After Initial Procedure (years)
No. at risk
7618
7375
6706
4533
2456
% CI
0.00
0.18
0.29
0.41
0.54
RESOLUTE Pooled – 5 Years
Conclusions
•
The current analysis of 7618 patients is the largest and longest dataset to date of
Resolute patients evaluated. While the complexity of patients varied by study,
approximately half of all patients had one or more complex patient characteristics.
•
Significant differences were observed in DAPT duration between trials and geographies,
reflective of different clinical practices around the world.
•
The event rates were stable through long-term follow-up. In particular, the rate of very
late ST (>1 yr, definite/probable) is low at 0.5% out to 5 years.
•
Long-term follow-up of current generation DES remains critically important to evaluate
if there is any increased risk over time of low frequency events. In this pooled analysis,
we did not observe any concerns of long term safety associated with the Resolute stent.
•
Over 5 years, more than half of the adverse events were not device (= stent) related,
indicating that we still need better general treatment options for patients with coronary
artery disease - even after stenting the culprit lesion(s).