A Randomized Comparison of a Sirolimus-eluting
Stent with Biodegradable Polymer versus an
Everolimus-eluting Stent with a Durable Polymer
for Percutaneous Coronary Revascularization
Thomas Pilgrim, MD
Swiss Cardiovascular Center
Bern University Hospital, Switzerland
A Meta-Analysis of Biodegradable Polymer DES
versus Durable Polymer Sirolimus Eluting Stents
Stefanini G et al. Lancet 2011; 378:1940-8
TLR
Definite ST
BP-DES DP-SES
ISAR-TEST 3
17/202
RR (95% CI)
21/202
0·81 (0·44, 1·49)
2 years fup
ISAR-TEST 4
ISAR-TEST 3
RR (95% CI)
1/202
2/202
0·50 (0·05, 5·47)
9/1299
9/652
0·50 (0·20, 1·26)
20/857
32/850
0·62 (0·36, 1·08)
2 years fup
168/1299 95/652
0·89 (0·70, 1·12)
3 years fup
LEADERS
BP-DES DP-SES
ISAR-TEST 4
3 years fup
88/857
111/850
0·79 (0·60, 1·02)
4 years fup
LEADERS
4 years fup
Overall (I-squared = 0·0%, p=0·79)
0·1
0·2
0·5
Favours
biodegradable
polymer DES
0·84 (0·71, 0·99)
1
2
5
Favours
durable
polymer SES
Overall (I-squared = 0·0%, p=0·92)
0·1
0·2
0·58 (0·37, 0·93)
0·5
Favours
biodegradable
polymer DES
1
2
5
Favours
durable
polymer SES
Biodegradable Polymer Based DES Platforms
Sirolimus – Genous
Bioengineered R Stent
Biolimus A9 – BioMatrix
Nobori, Axxess, XTENT
Everolimus - SYNERGY
Sirolimus – ORSIRO
Myolimus – ELIXIR
100%
% Myolimus
Released
Sirolimus – ISAR TEST
80%
60%
40%
20%
0%
0
3
28
90
Number of Days
Orsiro1 Hybrid Sirolimus Eluting Stent System
Passive component: PROBIO
• Silicon carbide2 layer that encapsulates the
stent surface, reducing ion release
Active component: BIOlute
• PLLA3 bioabsorbable polymer matrix
• Sirolimus (1.4 µg/mm2)
• Controlled drug release out to 3 months
• Asymmetric coating with greater
drug dose on abluminal side
In vivo drug release in minipig coronary arteries
(Ablumial thickness 7.4 µm)
100
Stent platform: PRO-Kinetic Energy
• Cobalt Chromium, L-605
• 60 µm struts
% Drug Release
90
80
70
60
50
40
30
20
10
0
1
Manufactured and distributed by BIOTRONIK
2 aSiC:H amorphous silicon carbide
3 Poly-L-lactide
0
10
20
30
40
50
60
Time (days)
Source: Data on file at BIOTRONIK
70
80
90
100
BIOSCIENCE Trial
NCT01443104
Prospective multi-center randomized “all-comers” trial with a non-inferiority design
2100 Patients
1:1
Orsiro® Stent system
Xience PRIME® stent
Sirolimus-eluting stent with a
biodegradable polymer
Everolimus-eluting stent with a
durable polymer
Primary endpoint:
Target lesion failure defined as the composite of cardiac death, target vessel
myocardial infarction, and clinically-driven target lesion revascularization at 12
months
Inclusion Criteria
1 Age ≥18 years;
2 Symptomatic coronary artery disease including patients with
chronic stable angina, silent ischemia, and acute coronary
syndromes including NSTE-ACS and STE-ACS;
3 Presence of one or more coronary artery stenoses >50% in a
native coronary artery or a saphenous bypass graft which can be
treated with a stent ranging in diameter from 2.25 to 4.0
mm
and can be covered with one or multiple stents;
4 No limitation on the number of treated lesions, and vessels, and
lesion length
Exclusion Criteria
1 Pregnancy;
2 Known intolerance to aspirin, clopidogrel, heparin, stainless steel,
Sirolimus, Everolimus or contrast material;
3 Inability to provide informed consent;
4 Currently participating in another trial before reaching first
endpoint;
5 Planned surgery within 6 months of PCI unless dual antiplatelet
therapy is maintained throughout the peri-surgical period
Follow-up
Clinical follow-up (visit) at 12 months;
Telephone follow-up at 30 days, 1, 2, and 5 years
Primary Endpoint
Target lesion failure (TLF) in the overall population, defined as the
composite of cardiac death, target vessel Q-wave or non-Q wave
myocardial infarction (MI) (i.e., Q-wave MI that cannot be attributed
to a non-target vessel), clinically driven target lesion
revascularization (TLR) and emergent coronary artery bypass grafting
(CABG) within 12 months.
Secondary Endpoints
Clinically indicated and not clinically indicated target lesion revascularization (TLR)
at 30 days, 1, 2 and 5 years.
Clinically indicated and not clinically indicated target vessel revascularization (TVR)
at 30 days, 1, 2, and 5 years.
TLF composite of cardiac death, target vessel Q-wave or non-Q wave myocardial
infarction (MI) (i.e., Q-wave MI that cannot be attributed to a non-target vessel),
clinically driven target lesion revascularization (TLR) and emergent coronary artery
bypass grafting (CABG)at 30 days, 2, and 5 years.
Target Vessel Failure (TVF) at 30 days, 1, 2, and 5 years.
Cardiac death at 30 days, 1, 2, and 5 years.
All deaths (cardiac and non-cardiac) at 30 days, 1, 2, and 5 years.
Myocardial infarction (Q-wave and NQWMI) at 30 days, 1, 2, and 5 years.
Definite stent thrombosis at 30 days, 1, 2, 3and 5 years.
Definite or probable stent thrombosis at 30 days, 1, 2, and 5 years.
Device success, lesion success and procedural success (see definitions).
Time Schedule
Event
Type of contact
Inclusion/
exclusion Criteria
Informed consent
Physical
examination
Medical and
Cardiac history
Anginal Status
CBC, blood
chemistry, lipids,
CK, CK-MB
Troponin
12 lead ECG
Medication
regimen
Adverse event
and Severe
Adverse Event
monitoring
Screen Procedur Post -Procedure
e
to Hospital D/c
30 Days
1 Yr
2 Yrs
5 Yrs
Phone
Visit
Phone
Phone
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Contacts
Dr. med. Thomas Pilgrim
Invasive Kardiologie, Inselspital Bern
thomas.pilgrim@insel.ch
076 548 44 11