A Randomized Comparison of a Sirolimus-elutingStent with Biodegradable Polymer versus an

Everolimus-eluting Stent with a Durable Polymerfor Percutaneous Coronary Revascularization

Thomas Pilgrim, MDSwiss Cardiovascular CenterBern University Hospital, Switzerland

Overall (I-squared = 0·0%, p=0·92)

LEADERS 4 years fup

ISAR-TEST 4 3 years fup

ISAR-TEST 3 2 years fup

20/857

9/1299

1/202

32/850

9/652

2/202

0·58 (0·37, 0·93)

0·62 (0·36, 1·08)

0·50 (0·20, 1·26)

0·50 (0·05, 5·47)

10·1 0·2 2 50·5

Favours biodegradable polymer DES

Favours durable

polymer SES

BP-DES DP-SES RR (95% CI)

Definite ST

A Meta-Analysis of Biodegradable Polymer DES versus Durable Polymer Sirolimus Eluting Stents

Stefanini G et al. Lancet 2011; 378:1940-8

Overall (I-squared = 0·0%, p=0·79)

LEADERS 4 years fup

ISAR-TEST 4 3 years fup

ISAR-TEST 32 years fup

88/857

168/1299

17/202

111/850

95/652

21/202

0·84 (0·71, 0·99)

0·79 (0·60, 1·02)

0·89 (0·70, 1·12)

0·81 (0·44, 1·49)

TLR

Favours biodegradable polymer DES

Favours durable

polymer SES

10·1 0·2 2 50·5

BP-DES DP-SES RR (95% CI)

Biodegradable Polymer Based DES Platforms

Sirolimus – ISAR TESTBiolimus A9 – BioMatrixNobori, Axxess, XTENT

Sirolimus – ORSIRO

Sirolimus – GenousBioengineered R Stent

Everolimus - SYNERGY Myolimus – ELIXIR

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 (Ablumial thickness 7.4 µm)

Stent platform: PRO-Kinetic Energy• Cobalt Chromium, L-605• 60 µm struts

1 Manufactured and distributed by BIOTRONIK2 aSiC:H amorphous silicon carbide3 Poly-L-lactide

In vivo drug release in minipig coronary arteries

0

10

20

30

40

50

60

70

80

90

100

0 10 20 30 40 50 60 70 80 90 100

% D

rug

Rele

ase

Time (days)

Source: Data on file at BIOTRONIK

BIOSCIENCE Trial NCT01443104

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

2100 Patients

Orsiro® Stent system Sirolimus-eluting stent with a

biodegradable polymer

Xience PRIME® stent Everolimus-eluting stent with a

durable polymer

1:1

Prospective multi-center randomized “all-comers” trial with a non-inferiority design

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 ScheduleEvent Screen Procedur

ePost -Procedure to Hospital D/c

30 Days 1 Yr 2 Yrs 5 Yrs

Type of contact Phone Visit Phone PhoneInclusion/

exclusion Criteria

X

Informed consent XPhysical examination

X

Medical and Cardiac history

X

Anginal Status X X X X X XCBC, blood chemistry, lipids,

X

CK, CK-MB X XTroponin X X12 lead ECG X XMedication regimen

X X X X X X X

Adverse event and Severe Adverse Event monitoring

X X X X X X

Contacts

Dr. med. Thomas Pilgrim

Invasive Kardiologie, Inselspital Bern

thomas.pilgrim@insel.ch

076 548 44 11