Transcript MY CONFLICTS OF INTEREST ARE I have accepted support for the

Prison II
Randomised Trial of SirolimusEluting and Bare Metal Stents in
Patients with CTO
(Presented at TCT 2005
Suttorp and Laarmen, Nieuwegein and Amsterdam)
MY CONFLICTS OF INTEREST ARE
I have accepted support for the purpose of attending
professional educational meetings from Boston Scientific, Cordis,
Medtronic and Guidant
I am in receipt of research funding from Boston Scientific
Background
• Angiographic restenosis rates with bare
metal stents in CTO :
– 22% Prison I
– 32% SICCO
(POBA 33%)
(POBA 74%)
Methods
• Single blind RCT, two centres
• Randomised after crossing a CTO > 2
weeks old
• Bx velocity vs. Cypher (n=200)
• Primary end point
– Binary Angiographic Restenosis at 6 months
• Secondary end points
– Clinical - MACE, TVF
– Angiographic - MLD, late loss, % stenosis
Results
• Baseline characteristics well matched:
– Mean age 59 years
– Diabetics 13%
– Single vessel disease 49%
– Mean stent length 30 mm
Results
Binary angiographic restenosis
45
40
73%
35
30
% 25
41
85%
36
BMS
SES
20
15
10
5
11
7
0
In segment
In stent
Results
Secondary End Points
• Angiographic
– Late loss +0.64 vs. -0.07 mm (p<0.001)
– % stenosis 53.3% vs. 31.9% (p<0.001)
• Clinical
– MACE 20% vs. 4%
– TLR 19% vs. 4%
– Stent thrombosis 0% vs. 2%
Conclusions
• First RCT showing that DES reduce
restenosis in CTO
• Is CTO another indication for DES?
ISAR TEST
Randomised comparison of a polymer
free sirolimus coated stent vs. polymer
based paclitaxel coated stent (Taxus)
Presented at TCT 2005
Kastrati et al. Munich
Background
Polymers may induce chronic inflammatory
reaction causing:
 delayed or incomplete re- endothelialization
 stent thrombosis
 restenosis
Methods
 Prospective RCT comparing a polymer-free sirolimus
stent with the polymer-based paclitaxel (!) stent
(Taxus Express2)
 n = 450
 Primary end point: in-stent late loss at 6 months
- Powered to determine non-inferiority (not equivalence) with a
margin of difference in late loss of 0.13 mm
 Secondary end points: BAR & TLR at 6 months
Stent Coating Machine and
Stent with Microporous Surface
A
B
100 µm
C
100 µm
D
10 µm
before
10 µm
after
Baseline Characteristics
• Well matched
– 43% unstable
– Mean lesion length 12.8 mm
– Mean vessel diameter 2.7 mm
– 1.1 stents per case
Results: Late Lumen Loss
0.6
mm
P = 0.98
0.48
0.48
0.4
0.6
P = 0.09
mm
0.4
0.34
0.24
0.2
0.2
0
0.0
Late lumen loss
Late lumen loss
(in-stent)
(in-segment)
Polymer-Free
Sirolimus Stent
Polymer-Based
Paclitaxel Stent
Angiographic and Clinical
Restenosis
Incidence, %
20
Incidence, %
P = 0.73
14.2
P=1
20
15.5
10
10
0
0
Angiog. Restenosis
Polymer-Free
Sirolimus Stent
9.3
9.3
Clinical Restenosis
(TLR)
Polymer-Based
Paclitaxel Stent
Conclusion
 The polymer-free sirolimus-eluting stent has an
anti-restenotic effect that is not inferior to that
of polymer-based paclitaxel-eluting stent.
Interpretation
• Early evidence of angiographic efficacy of
non polymer ‘DIY’ sirolimus eluting stent
• Clinical efficacy?
• How important is the polymer ?
– Results attributable to lack of polymer or different drug?
ENDEAVOR III
Prospective randomized comparison of
Endeavor zotarolimus-eluting stent
with Cypher sirolimus-eluting stent
(Presented at TCT 2005
PIs David E. Kandzari and Martin B. Leon)
ENDEAVOR III
Hypothesis:
Treatment with the Endeavor
zotarolimus-eluting stent will be noninferior compared with the Cypher
sirolimus-eluting stent with respect to insegment late lumen loss
Head to Head Non Inferiority Trial
ENDEAVOR III - Design
3:1 Randomization
Single de novo native coronary lesion
Vessel diameter: 2.5-3.5 mm
Lesion length: 14-27 mm
Stent lengths: 18-33 mm
Endeavor Stent
n=327
Io Endpoint:
436 patients
30 U.S. sites
Cypher Stent
n=109
In-segment late loss at 8 months
(powered for a margin of difference of 0.2 mm)
2o Endpoints: Angiographic binary restenosis at 8 months;
Clinical TLR, TVR, TVF at 9 months
Baseline Characteristics
• Imbalanced for gender
– 65% male Endeavor, 85% male Cypher (p<0.01)
• Otherwise well balanced
– Diabetes 29%, unstable 53%,
• Procedure success
– 99% Endeavor, 95% Cypher (p<0.002)
Results: Primary End Point
In-segment Late Loss
0.4
0.3
(mm)
0.2
0.21 mm
0.34
0.1
Endeavor
Cypher
0.13
0
Non-Inferiority Margin of Difference:
0.20 mm
Observed Difference:
0.21 mm
p = NS for non-inferiority, <0.001 for Cypher superiority
% of Patients
Distribution of Late Loss
30
25
Endeavor
Cypher
0.34±0.44
0.13±0.32
20
15
10
5
0
-0.6
-0.2
0.2
0.6
1.0
1.4
Insegment LLL (mm)
1.8
2.2
2.6
mm
Angiographic End Points
0.6
12
0.5
10
0.4
8
%
0.3
Endeavor
Cypher
0.2
0.1
0
6
Endeavor
Cypher
4
2
In stent
In
segment
Late Loss
0
In stent
In
segment
Binary Restenosis
Clinical End Points
TVF Free Survival to 270-days
88.5%
100%
90%
Freedom from TVF
80%
88. 0%
70%
60%
P=0.923, log rank
50%
40%
30%
20%
10%
Cypher
ENDEAVOR
0%
0
30
60
90
120
150
180
210
240
270
Time after Initial Procedure (days)
No difference in MACE, TVF, TLR, death…
Conclusions
The non-inferiority primary endpoint of insegment late loss was not met
i.e. Endeavor was not not (= was) inferior to
Cypher
No significant differences in 9 month clinical
outcomes (TLR, MACE, TVR and TVF)
Interpretation
“Endeavor angiographically inferior but
clinically equivalent”?
Which is the better discriminator of
restenosis propensity: angiographic late
loss or clinical events ?
“Late loss is more reliable than restenosis
rates for discriminating restenosis
propensity between new drug eluting stent
platforms…”
Circ 2005,112 2833
BM
En
Cy
Ta
Circ 2005; 111: 3435