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Biodegradable polymer SES vs
permanent polymer EES in patients
with coronary artery disease
5-year outcomes from ISAR-TEST 4
EuroPCR, Thurs 22nd May 2014
Robert A. Byrne MB BCh PhD FESC
Deutsches Herzzentrum, Technische Universität, Munich
Potential conflicts of interest
Speaker's name: Robert A. Byrne MB BCh PhD FESC
I have the following potential conflicts of interest to report:
Consultant:
Employment in industry:
Honorarium: B. Braun, Biotronik
Institutional grant/research support:
Owner of a healthcare company:
Stockholder of a healthcare company:
Delayed Arterial Healing After DES
*
PRT
Byrne, Joner, Kastrati Minerva Cardiol 2009
Delayed Arterial Healing Spectrum
Thr
Late Luminal Creep
Late Stent Thrombosis
Vasomotor Dysfunction
De novo In-stent
Atherosclerosis
Durable Polymer Associated Inflammation
Giant cells
Fibrin
Eosinophils
Calcification
Giant cells
polymer delamination
28 days
90 days
Giant cells
90 days
Polymer destruction
ISAR-TEST Stent Programme
Aim: to develop a high efficacy, high
performance workhorse DES without
resort to durable polymer coatings
Yukon Choice PC
A combination of microporous stent surface, reduced quantity of PDLLA
biodegradable polymer and sirolimus
Before coating
Wessely et al, ATVB 2005
After coating
Steigerwald et al, Biomaterials 2009
• Micropores act like drug reservoirs that use Van-der-Waals forces to control the releasekinetics of the drug
• The microporous surface enables a minimum load of PDLLA biodegradable polymer (<1/4th
of the polymer load in other DES) which is degraded in 60 days
Release Kinetics and Antirestenotic Efficacy
ISAR-TEST 3
(A)
(B)
Drug release kinetics
Late luminal loss at 6-8 months
0,6
100
mm
%
0,47
p<0.001
80
0,4
60
0,23
40
0,2
0,17
Yukon Polymer-free
Cypher*
Yukon Choice PC
20
0
0
100
200
300
400
Time (hours)
*approximated
500
600
700
0
Yukon
Choice PC
Mehilli et al. EHJ 2008; Byrne et al. Heart 2009
Cypher
Polymer
Free
ISAR-TEST 4
2603 pts
Yukon Choice PC
(BP Sirolimus)
Cardiac death, target vessel MI, TLR
Byrne et al., EHJ 2009
Cypher or Xience
(PP Siro-/everolimus)
But…
…the hypothesized clinical
advantage of BP-DES is expected
to accrue with time
ACC Featured Clinical Study 2012
Randomized patients treated with biodegradable polymer DES or
durable polymer sirolimus-eluting stent in
ISAR-TEST 3, ISAR-TEST 4, LEADERS
(n= 4062)
Biodegradable polymer stent
(n= 2358)
Durable polymer stent
(n= 1704)
Sirolimus-eluting stent
Biolimus-eluting stent
(Yukon Choice PC)
(Biomatrix Flex)
(n= 1501)
(n= 857)
Sirolimus-eluting stent
(Cypher)
(n= 1704)
4-year clinical follow-up
4-year clinical follow-up
4-year clinical follow-up
Stefanini, Byrne et al. Eur Heart J 2012
BP-DES vs. PP-DES Definite Stent Thrombosis
Years after randomization
Stefanini, Byrne et al. Eur Heart J 2012
BP-DES vs. PP-DES Definite Stent Thrombosis
Years after randomization
Stefanini, Byrne et al. Eur Heart J 2012
BP-DES vs. PP-DES Target Lesion Revascularization
Years after randomization
Stefanini, Byrne et al. Eur Heart J 2012
But…
…the first generation sirolimuseluting Cypher stent is no longer
the comparator of choice
ISAR-TEST 4: Final 5-Year Data
Study Design
Randomized patients
(n= 2603)
Biodegradable polymer stent
(n= 1299)
Permanent polymer stent
(n= 1304)
Sirolimus-eluting stent
(n= 652)
Kufner et al. under review
Everolimus-eluting stent
(n= 652)
ISAR-TEST 4: Final 5-Year Data
Cardiac death/target vessel MI/TLR
50
%
40
HR 1.04 [95% CI, 0.84-1.29], P=0.71
30
Biodegradable polymer Yukon Choice PC 20.5%
20
Permanent polymer Xience 19.5%
10
0
0
1
2
3
Kufner et al. under review
4
Years
5
ISAR-TEST 4: Final 5-Year Data
Definite/probable stent thrombosis
5
%
4
HR 0.83 [95% CI, 0.37-1.91], P=0.67
3
2
Permanent polymer EES (Xience) 1.4%
1
Biodegradable polymer SES (Yukon Choice PC) 1.2%
0
0
1
2
3
Kufner et al. under review
4
Years
5
ISAR-TEST 4: Final 5-Year Data
Cardiac death/target vessel MI
20
%
HR 0.99 [95% CI, 0.72-1.37], P=0.97
15
Biodegradable polymer Yukon Choice PC 8.9%
10
Permanent polymer Xience 8.9%
5
0
0
1
2
3
Kufner et al. under review
4
Years
5
ISAR-TEST 4: Final 5-Year Data
Target lesion revascularization
50
%
40
HR 1.11 [95% CI, 0.85-1.45], P=0.46
30
20
Biodegradable polymer Yukon Choice PC 13.9%
10
Permanent polymer Xience 12.6%
0
0
1
2
3
Kufner et al. under review
4
Years
5
ISAR-TEST 4: Final 5-Year Data
Hazard Ratio (95% CI)
All
P-value
1.04 (0.84 – 1.29)
Age
1.02 (0.77 – 1.36)
1.09 (0.79 – 1.51)
0.89
0.60
Women
Men
Diabetes
0.84 (0.56 – 1.27)
1.12 (0.87 – 1.44)
0.42
0.38
Yes
No
Myocardial infarction
1.07 (0.73 – 1.57)
1.03 (0.79 – 1.33)
0.72
0.84
0.76 (0.43 – 1.37)
1.09 (0.86 – 1.37)
0.37
0.48
1.00 (0.75 – 1.34)
1.09 (0.79 – 1.50)
0.80
0.79
>67.6 yrs
≤67.6 yrs
Sex
Yes
No
Vessel size
<2.73 mm
≥2.73 mm
0.5
Biodegradable polymer
Yukon Choice PC better
1
Hazard Ratio
(95% CI)
1.5
2
Permanent polymer
Xience stent better
Biodegradable polymer SES vs permanent
polymer EES in patients with coronary disease
Final 5-year outcomes from ISAR-TEST 4
In the ISAR-TEST 4 we demonstrated non-inferiority of a microporous
thin-strut biodegradable polymer Yukon Choice PC SES versus
permanent polymer Cypher SES and Xience EES at 12-months
Pooled 4-year data with ISAR-TEST 3 and LEADERS showed superior
clinical outcomes in comparison with permanent polymer Cypher SES
Final 5-year follow-up data demonstrates comparable clinical
outcomes between biodegradable polymer Yukon Choice PC SES and
the permanent polymer Xience EES in terms of overall target lesion
failure, stent thrombosis and target lesion revascularization
Thank you for your attention
Robert A. Byrne, Deutsches Herzzentrum, Munich
[email protected]
ISAR-TEST 4: Final 5-Year Data
Stent thrombosis
3
Permanent polymer SES
Biodegradable polymer SES
Permanent polymer EES
2
1.5%
1.4%
1.0%
1
0.9%
0.2%
0.0%
0
0
1
2
3
Kufner et al. under review
4
Years
5

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