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Trial Vignettes
Contemporary trials 3: DES
Angela Hoye
Castle Hill Hospital, Hull
RESOLUTE
MEDISTRA
ABSORB
Conflicts of interest
• Speaker honorarium: Cordis
• Advisory board panel: Eli Lilly
Abbott Vascular
RESOLUTE
• Multicenter study, n=130, PI Prof Meridith
• The Endeavor Resolute stent (Medtronic)
retains 3 components of Endeavor
Driver Cobalt Chromium Stent
Endeavor Delivery System
 Extended
drug-elution
Zotarolimus Antiproliferative Drug
The BioLinx Polymer System
Hydrophilic
Zotarolimus
Hydrophobic
Hydrophilic polymer: Polyvinyl pyrrolidinone (PVP) for initial drug burst
and enhanced biocompatibility
Hydrophobic polymer: based upon hydrophobic butyl methacrylate (C10)
for combining with zotarolimus and uniform drug dispersion
Combination polymer: hydrophobic hexyl methacrylate, hydrophilic vinyl
pyrrolidinone and vinyl acetate (C19) to support delayed drug elution and
biocompatibility
Endeavor Resolute Elution
Extended in vivo elution kinetics with stent drug content exhausted by 180 days
Carter et al TCT2006
Endeavor Resolute Efficacy
28 day results in porcine coronary artery
DRIVER
CONTROL
ENDEAVOR
RESOLUTE
ENDEAVOR
RESOLUTE
Significant inhibition of neointimal development
compared to Driver controls
Carter et al TCT2006
Clinical Trial Design
Single De Novo Native Coronary Artery Lesions
Lesion Length: 14-27mm
Stent Diameters: 2.5, 3.0, 3.5mm
Stent Lengths: 18, 24, 30mm (8/9mm bailout)
Drug Dose: 1.6 g/mm2 stent surface area
Antiplatelet therapy for 6 months
Pre-dilatation required
Endeavor Resolute
Stent
130 Patients (includes 30 PK Sub-Study Patients)
12 Sites (New Zealand and Australia)
Clinical/MACE
30d
4mo 6mo
9mo
12mo
2yr
3yr
4 yr
Angio/IVUS
N=30
N=100
Primary Endpoint: Late lumen loss (in-stent) at 9 months by QCA
Secondary Endpoints: MACE at 30 days, 6, 9 and 12mths and IVUS and
angiographic parameters at 9mths
9 month results will be compared to ENDEAVOR II DES cohort
30 pt Subset: 4mth MACE and angiographic, IVUS parameters
5 yr
Patient Demographics
Male
Age
Prior MI
Prior PCI
Diabetes Mellitus
Insulin Dependent
Unstable Angina
Hyperlipidemia
Current Smoker – within last
30 days
75.4%
61 + 10yrs
45.7%
18.5%
17.7%
2.3%
29.7%
94.6%
22.3%
(98/130)
(130)
(59/129)
(24/130)
(23/130)
(3/130)
(38/128)
(123/130)
(29/130)
Procedural Results
Entire patient cohort 130 pts/131 lesions
Lesion Length
LAD
15.56 + 6.27 mm
34.4% (45/131)
B2/C Lesions
82.4% (108/131)
Device success
Procedure success
Lesion success
Device success
Procedure success
99.2%
96.2%
<50% residual in-segment % ds
<50% residual in-segment % ds with assigned stent
<50% residual in-segment % ds & without 30-day MACE
Clinical Results to 30 days
Entire patient cohort
n = 130
3.8
(5/130)
Death
Q-Wave MI
Non Q-Wave MI
0
0
3.8
(0/130)
(0/130)
(5/130)
Emergent CABG
TLR
0
0
(0/130)
(0/130)
TL-CABG
0
(0/130)
TL-PCI
0
(0/130)
TVR (non-TL) (%)
Stent Thrombosis (%)
0
0
(0/130)
(0/130)
MACE (%)
Angiographic results
Subset n=30
RVD (mm)
In-stent
In-segment
2.90±0.38
Lesion Length (mm)
MLD (mm) pre
post
2.81±0.36
15.16+5.38
0.83+0.34
2.43±0.45
Acute Gain
1.98±0.45
1.61±0.59
MLD (mm) 4 mo f/u
Late Loss (mm)
Late Loss Index
% DS
ABR (%)
2.68±0.39
0.12±0.26
0.06+0.17
7.18±7.86
0
2.38±0.40
0.05±0.20
0.01+0.18
17.74±7.57
0
IVUS Volumetric Results
Subset n=30
Post Procedure
4 mo Follow up
EEM Volume
345.5 + 110 mm3
337.5 + 88.1 mm3
Stent Volume
170.7 + 58.8 mm3
167 + 44.8 mm3
Neointimal Volume
0.42 + 1.15 mm3
3.72 + 4.21 mm3
(mm2)
IVUS Cross-sectional area results: (serial IVUS (2D & 3D analysis, n=29)
10
8
6
4
2
0
6.7 ± 1.6
6.8 ± 1.7
Post Stent
Follow up
P=NS
Conclusions
• Excellent rate of device, lesion and procedural
success
• Low clinical adverse event rate at 30 days
• The angiographic and IVUS results observed in
the 4 month subset demonstrated low late loss,
and minimal neointimal hyperplastic in-growth
Medistra Excel Drug-ElutIng Stent TRiAl
• Single center registry of “real world” cases
• PI Dr Santoso, Medistra Hospital, Jakarta
Platform: S-Stent
Strut thickness 0.0047”
Carrier :
Biodegradable
EXCEL
PLA polymer
JW Technologies
Drug :
Sirolimus
40％of Sirolimus released in an initial 24 h, followed
by a constant slow release (3-6 months)
Lower cost: $1,200
28-day preclinical study results
without Sirolimus
with Sirolimus
Medistra Excel Drug-ElutIng Stent TRiAl
Single center, prospective, observational study (2004-06)
Study NOT sponsored by the company
Inclusions:
All comers who are candidates for PCI
(“real world cases”)
Exclusions:
Contraindications to anti-platelets
Patients with short life expectancy &
concomitant disease (advanced cancer, etc)
Lack of patient’s consent
serious
Medistra Excel Drug-ElutIng Stent TRiAl
Primary End-Point:
TLR at 6 and 12 months
Secondary End-Points:
6-month in-segment restenosis rate
In-segment late loss
Major Adverse Cardiac Events (MACE):
Death, QMI, NQMI, & / or TLR
QCA analysis was done by an independent core laboratory
(National Heart Centre - Singapore)
(Dr. A. Wong, A/Prof. T.H. Koh)
Medistra Excel Drug-ElutIng Stent TRiAl
Predilatation is encouraged, even though direct stenting
is allowed in simple lesion
Stent selection:
Try to always use EXCEL
If appropriate size / length not available, use other DES
(Cypher or Taxus)
If other DES is not available (logistic problem), use
BMS
• Antiplatelet regimen:
• ASA 160 mg indefinitely (unless contraindicated)
• Clopidogrel 300 mg (loading), then 75 mg for 6 months
Methods
All comers,
N = 279
2 stent
dislodgement*
(“prototype stent”)
277 eligible pts, 631 lesions
DES-stenting as default strategy (N=771 stents),
except if there is logistic problem (BMS will be used)
EXCEL
CYPHER
TAXUS
BIOMATRIX
ENDEAVOUR
BMS
N=470
N=137
N=86
N=27
N=5
N=46
* 1 case when negotiating mildly stenotic, acutely angulated LCX to fix mid-LCX stenosis
1 case with diffuse, calcified mid-RCA stenosis, during attempted direct stenting
61% of stents
Demographics (n=277)
• Age (yrs)
58.5 + 9.4
• Male
226 (81.6%)
• Family history
97 (35. 0%)
• Hypertension
152 (54.9%)
• Dyslipidemia
160 (57.8%)
• Diabetes mellitus
110 (39.7%)
• Smoking
119 (43.0%)
• Prior MI
123 (44.4%)
• Prior CABG
14 (5.0%)
• Prior PCI
77 (22.8%)
Clinical Presentation
Clinical presentation
Stable angina
Unstable angina / ACS
Acute MI
Recent MI ( < 30 days)
Silent ischemia
LVEF (%, mean + SD)
133 (48.0%)
32 (11.6%)
11 (4.0%)
15 (5.4%)
86 (31.0%)
59 + 11%
Lesion types
SVG
0.7
LM
1.2
ISRS
5.8
Thrombus
13.7
CTO
14.1
Bifurcation
18.4
Long>25mm
19.1
Calcification
28.1
DM
39.7
Small vessel
49.3
Type B2/C
85.3
0
20
40
60
80
100
%
Stent Diameter (n=771 stents)
EXCEL (n=470)
2.5 mm
3.0 mm
TAXUS (n=86)
3.5 mm
2.5 mm
3.0 mm
15
%
48
%
2.75 mm
3.5 mm
15
30
22
37
33
BMS (n=46)
CYPHER (n=137)
2.5 mm
3.0 mm
9
%
2.5 mm
3.5 mm
2.75 mm
3.5 mm
3.0 mm
4.0 mm
17
27
41
31
%
33
22
24
BIOMATRIX (n=27): 2.5 mm:16; 3 mm:5; 3.5 mm:3; 4 mm:3
ENDEAVOUR (n=5): 2.5 mm:2; 3 mm:2; 3.5 mm:2
Clinical results
30 days
No. pts
Death
Non-fatal MI
TLR/TVR
CABG
Stent
thrombosis
6 months
12 months
232 (84%) 210 (76%)
2 (0.9%) *+ 2 (1.0%)
0
0
4 (1.9%)
1 (0.4%)*
154 (51%)
2 (1.3%)
0
6 (3.9%)
0
2 (0.9%)*
0
2 (1.0%)
0
2 (1.3%)
* Pt with diffuse small LAD disease, multiple overlapped Cypher & Excel stents
+ Pt with triple, small vessel disease, died 1 week after PCI (5 stents: Excel,
BioMatrix & Cypher)
QCA analysis at 6 months
(independent QCA lab – NHC, Singapore)
QCA analysis: 94 pts with 217 lesions
34% of the total
patient cohort
Types of Stents used (per lesion)
Cypher
Taxus
EXCEL
BMS
(n=34)
(n=30)
(n=138)
(n=15)
Lesion length(mm)15.8
18.3
15.8
12.3
Stent size (mm)
2.85
2.87
2.86
3.50
Stent length (mm) 22.5
26.8
21.7
16.8
QCA analysis at 6 months
CYPHER
TAXUS
EXCEL
BMS
Pre procedural
RVD, mm
MLD, mm
DS, %
2.60
0.93
57.3
2.57
0.95
62.2
2.53
0.97
60.0
3.20
1.09
66.0
Post procedural
MLD, mm
DS, %
2.13
17.7
2.11
18.8
2.08
17.7
2.73
12.8
1.78
31.7
10%
2.07
21.6
5%
2.06
35.9
17%
0.31
(p=0.03)
0.01
0.55
(p=0.003)
0.35
(p=0.004)
0.07
0.59
(p<0.001)
Follow-up (6 months)
MLD, mm
1.89
DS, %
29.2
Binary restenosis 18%
Late loss, mm
In-segment
0.24
(p=0.12)
In-stent
0.25
(p=0.055)
Conclusion
Despite the inclusion of challenging “real
world cases” (DM, MVD, small vessel, complex
lesions, long – diffuse disease, calcified stenosis, ostial
stenosis, LM, AMI, CTO, instent restenosis, etc)
the preliminary EXCEL results are
encouraging,
with very low MACE rate & “clean”
angiographic appearance of the stent.
ABSORB study
• FIM study of the BVS everolimus-eluting
bioabsorbable stent from Abbott Vascular
• Preliminary results presented by Dr J Ormiston
ML VISION™
Balloon SDS
BVS
bioabsorbable
stent platform
A polymeric stent made
from linked polylactic
acid molecules that break
down into lactic acid
Everolimus
Bioabsorbable
Polymer Coating
Porcine Coronary Artery Safety
Study: Representative Photomicrographs (10x)
BVS
28 Day
90 Day
180 Day
270 Day
Competitive Metallic DES*
28 Day
90 Day
180 Day
270 Day
*CYPHER ®
Product currently in development at Abbott Vascular. Not available for sale.
SE 2925096/B
ABSORB STUDY
• FIM study of 30 patients with single de novo native
lesions
• The stent used was 3.0 x 12 mm
• Cypher stents were used if necessary as “bailout”
• PIs Dr Ormiston, Prof Serruys
Pre
Product currently in development at Abbott Vascular. Not available for sale.
Final
SE 2925096/B
Baseline Lesion Characteristics:
Acute Success
n=30
Location:
Lesion classification:
Clinical device success:
LAD
RCA
LCx
B1
B2
47%
23%
30%
60%
40%
93.5%
- successful delivery & deployment of stent with final residual DS of <50%. Bailout patients will
be included as device success only if the above criteria for clinical device are met.
Clinical procedure success:
100%
- definition above and/or using any adjunctive device without occurrence of ischemia driven
MACE during first 7 days
Bailout Stents = 4 patients: Two patients had procedure dissections treated with single
CYPHER® stents, one patient received a CYPHER® stent for vessel step-down and one
patient received three CYPHER® stents to treat the target lesion.
In-Stent Baseline QCA
N = 30
Pre-procedure
Lesion length (mm)
RVD (mm)
MLD (mm)
DS (%)
9.05
2.69
1.06
60
N = 26*
Post-procedure
MLD (mm)
DS (%)
Acute gain (mm)
2.31
17
1.22
* Per treatment evaluable population. Four patients excluded that received a non-BVS bail out stent,
including one patient that did not receive a BVS stent at the target lesion
Acute Recoil (n=27*)
Average of Mean Lumen Diameter (mm)
Stent
Expansion
2.86
Post Stent
Expansion
Absolute Stent
Recoil
Relative Stent
Recoil
2.67
0.20
6.85%
Ref: S. Tanimoto et al: Acute Stent Recoil of a Bioabsorbable
Everolimus Eluting Coronary Stent: In Vivo Evaluation; e-Poster
presentation number 306, TCT 2006.
Recoil rate for XIENCE™ V stent 4.27% (p=0.25)
*Subgroup analysis, recoil data not available in three patients
Clinical Results
Hierarchical MACE at 30
Days
Cardiac Death %
Myocardial Infarction %
Q-wave MI
Non Q-wave MI
N = 26
0
0
Ischemia driven TLR %
CABG
PCI
0
MACE %
Stent thrombosis %
0
0
Conclusions
• In this FIM study of a bioabsorbable
everolimus-eluting stent, there was low
acute stent recoil
• There was a high rate of procedural
success (100%)
• At 30 days, there were no cardiac
deaths, no MI, no stent thrombosis, and
no TLR
Summary
• Encouraging preliminary results with
all three stents
– Zotarolimus-eluting Endeavor Resolute
stent (Medtronic)
– Sirolimus-eluting Excel stent (JW
Technologies)
– Bioabsorbable everolimus-eluting stent
(Abbott Vascular)
Thankyou