1. Safety and Clinical Performance of the Drug- Eluting Orsiro Stent in the Treatment of Subjects With Single De Novo Coronary Artery Lesions-II (BIOFLOW-II , NCT )
Stephan Windecker, Bernhard Witzenbichler, Karl Stangl, Ton Slagboom, Franz-Josef Neumann, Thierry Lefévre, Rafael Ruiz-Salmeron,
Manel Sabaté, Christophe Piot, Gert Richardt, Béla Merkely,
Javier Goicolea, Johannes Bilger, Henrik Schneider, Paul Barragan,
Stéphane Cook, Paul Erne, Ron Waksman, Michael Haude

2. Potential conflicts of interest
Speaker's name: Stephan Windecker
 I have the following potential conflicts of interest to report:
Consultant: NA
Employment in industry: NA
Honorarium: NA
Institutional grant/research support:
Abbott, Biosensors, Biotronik, Boston Scientific, Cordis, Edwards Lifesciences, Medtronic, St Jude
Owner of a healthcare company: NA
Stockholder of a healthcare company: NA

3. Everolimus-Eluting Versus Sirolimus-Eluting Durable Polymer Stents
Target Lesion Revasc
Definite ST
Favors EES
Favors SES
Favors EES
Favors SES
Meta-Analysis N = 11,167

4. Biodegradable Polymer DES Versus Durable Polymer SES @ 4 Years
Target Lesion Revasc
Definite ST
Favors BP DES
Favors SES
Favors BP DES
Favors SES
N = 4,062 – IPD Pooled Analysis of LEADERS, ISAR-TEST 3 and 4
Stefanini G et al. Eur Heart J 2012; 33, 1214–1222

5. BIOFLOW-II Trial Primary Objective
To compare the ORSIRO® sirolimus-eluting stent with biodegradale polymer (BIOTRONIK) with the XIENCE Prime® everolimus-eluting stents (Abbott Vascular) with durable polymer for the treatment of de novo coronary lesions with respect to non-inferiority for in-stent Late Lumen Loss (LLL) at 9 months

6. BIOFLOW-II Trial - Stent Platforms
Co-Cr, L-605
60 µm
Stent material
Strut thickness
Passive coating
Silicon carbide
Polymer coating
Biodegradable (PLLA)
Drug
Sirolimus
Orsiro
81 µm -
Durable (PBMA/PVDF-HFP)
Everolimus
Xience Prime™

7. BIOFLOW II – Study Design
440 Patients with stable CAD
2:1 randomization
Orsiro
Xience Prime
Clinical follow-up at 1 and 6- month
Clinical, angiographic, IVUS* and OCT*
at 9 months follow-up
* Pre-specified subgroups with 60 patients in each
Clinical follow-up at 12 months
Clinical follow-up to 5 years
Primary Endpoint: In-Stent Late Lumen Loss at 9 months follow-up

8. Patients Eligibility Inclusion Criteria Exclusion Criteria
Single de novo lesions (≥ 50% and <100%) in up to 2 native coronary arteries
RVD ≥2.25 mm and ≤4.0 mm
Lesion lengths ≤26 mm
Age ≥ 18 years and ≤ 80 years old
Target vessel(s) TIMI flow ≥ 2
Eligible for DAPT therapy with ASA plus either, Clopidogrel, Prasugrel, Ticlopidine, or Ticagrelor
Evidence of myocardial infarction within 72 hours prior to index procedure
≥2xURL CK level or in absence of CK a ≥3xURL CKMB <24 hours prior to PCI
Unprotected left main
3-Vessel CAD
Thrombotic lesions
Ostial lesions
Bifurcation lesions (SB > 2.0 mm)
LVEF ≤ 30%
Heavily calcified lesion
Lesions in bypass graft
Serum creatinine > 2.5 mg/dl

9. Sample Size Calculation
Assumptions
Mean in-stent late lumen loss mm
Standard deviation mm
Non-inferiority margin mm
Average number of lesion/patient
Ration of random allocation :1
Attrition rate %
Sample Size
Overall sample size of 440 randomised subjects (293 in the Orsiro group and 147 in the Xience Prime group) or 352 subjects with angiographic follow-up (234 in the Orsiro group and 118 in the Xience Prime group) will yield a power of 1-β = 80% at a two-sided α = 5%

10. Trial Organization Co-Principal Investigators Sponsor
S. Windecker, Bern, Switzerland T. Lefèvre, Massy, France
Sponsor
Biotronik
Core-Laboratories
MedStar Health Research Institute (Angiography and IVUS)
Cardialysis B.V. (OCT)
Data Analysis
Clinical Trials Unit Bern, Bern, Switzerland
Clinical Event Committee
Ralf Birkemeyer, Rostock, Germany
Harald Rittger, Erlangen, Germany
Zbigniew Siudak, Krakow, Poland

11. BIOFLOW II - Patient Flow
452 patients randomized (ITT*) between July 2011 and March 2012
Randomization
2:1
298 Orsiro Angio: n=298 IVUS: n=40 OCT: n=44
154 Xience Prime Angio: n=154 IVUS: n=26 OCT: n=21
1-month FUP Clinical: n =294 (99%)
1-month FUP Clinical: n =151 (98%)
6-month FUP Clinical: n =293(98%)
6-month FUP Clinical: n =151 (98%)
9-month FUP
Clinical: n=288 (97%)
Angio: n=252 (85%)
IVUS: n=32 OCT: n=37
9-month FUP
Clinical: n=151 (98%) Angio: n=131 (85%) IVUS: n=23 OCT: n=17
Clinical FUP yearly up to 5 years ongoing
*ITT= Intention to treat

12. 452 patients were enrolled across 24 centers in 8 European countries
Investigator
Country
Patients
M. Haude, MD
Germany 57
P. Erne, MD
Switzerland 41
B. Witzenbichler, MD 34
K. Stangl, MD 31
F.J. Neumann, MD 28
T. Slagboom, MD
Netherlands
S. Windecker, MD 24
T. Levefre, MD
France
R. Salmeron, MD
Spain 20
M. Sabate, MD
C. Piot, MD 18
G. Richardt, MD
B. Merkely, MD
Hungary 15
J. Goicolea, MD 14
H. Schneider, MD
J. Bilger, MD
P. Barragan, MD 12
S. Cook, MD 11
T. Moccetti, MD 9
A. Erglis, MD
Latvia 8
W. Scholtz, MD 7
B. Eber, MD
Austria 5
P. Radke, MD 3
M. Roffi, MD
452 patients were enrolled across 24 centers in 8 European countries
Main study + OCT
Main study
Main study + IVUS

13. Baseline Clinical Characteristics
Orsiro
(N=298 Patients)
Xience Prime
(N=154 Patients)
Age, years mean ± SD
62.7 ± 10.4
64.8 ± 9.2
Gender male (%)
78.2
74.7
Hypertension (%)
77.5
73.7
Hyperlipidemia (%)
67.8
73.4
History of MI (%)
30.2
20.1
Renal Insufficiency (%)
7.0
4.5
Congestive Heart Failure (%)
10.1
13.6
Diabetes (%)
28.2
28.6
Insulin dependent (%)
21.4
34.1
Non-insulin dependent (%)
78.6
65.9
Smoking (%)
66.4
57.8
History of stroke TIA (%)
6.5

14. Baseline Lesion Characteristics
Lesion Location
Lesion Type

15. Procedural Characteristics
Orsiro
(N=332 Lesions)
Xience Prime
(N=173 Lesions)
Preprocedure
Lesion length (mm)
13.36 ± 6.82
13.65 ± 5.58
Reference Vessel Diameter (mm)
2.78 ± 0.49
2.75 ± 0.49
Minimum Lumen Diameter (mm)
0.93 ± 0.46
0.96 ± 0.46
Diameter stenosis (%)
66.73 ± 14.27
65.34 ± 14.52
Postprocedure
In-stent
2.62 ±0.45
2.58 ± 0.41
In-segment
2.33 ±0.48
2.31 ±0.45
6.91 ± 7.25
7.07 ± 7.70
17.44 ± 7.00
17.42 ± 6.64
Device success (%)
100
Procedure success (%)
97.5

16. P non-inferiority = <0.0001
Primary Endpoint
In-stent 9-Months
9 Month In-Stent LLL (mm)
Cumulative Frequency (%)
P non-inferiority = <0.0001
Difference = 0.00
95% CI = to 0.06
0.10 ± 0.32 mm
0.11 ± 0.29 mm
Orsiro
Xience Prime

17. Angiographic Follow-up Findings
Orsiro
(N=278 Lesions)
Xience Prime
(N=149 Lesions) P
Late loss (mm)
In stent
0.10± 0.32
0.11 ± 0.29
0.99
In segment
0.09 ± 0.35
0.09 ± 0.33
0.86
MLD (mm)
2.52 ± 0.56
2.48 ± 0.50
0.40
2.25 ± 0.55
2.22 ± 0.56
0.59
Diameter stenosis (%)
9.52 ± 13.49
9.43 ± 10.78
0.89
19.48 ± 12.89
19.22 ± 12.25
0.96
Binary restenosis (%)
6 (2.16%)
2 (1.34%)
0.56
11 (3.96%)
7 (4.70%)
0.72
Remove In stent LLL Keep rest

18. Target Lesion Failure Through 9 Months
TLF (%)
0.0%
5.0%
10%
15%
Days after PCI 30 60 90
120
150
180
210
240
270
Orsiro
Xience Prime
5.3%
4.8%

19. Target Lesion Failure Clinical Outcome @ 9 Months
(%)
P=0.40
P=0.95
P=0.66
P=0.47
TLF, composite of cardiac death, target vessel MI (Universal Definition),
clinically driven TLR and emergent CABG - time to first event
All events have been adjudicated by an independent clinical event committee 19

20. Stent Thrombosis Through 9 Months
Definite ST
Definite or Probable ST
Orsiro
(N=298)
Xience Prime
(N=154)
Acute (0-48h)
0 %
Subacute (48h-30d)
Late (>30d-9m)
Overall
Orsiro
(N=298)
Xience Prime
(N=154)
Acute (0-48h)
0 %
Subacute (48h-30d)
Late (>30d-9m)
Overall

21. Apposition and Coverage
OCT 9 Months
Neointimal Area
Apposition and Coverage 10 20 30 40 50 60 70 80 90
100
0.2
0.4
0.6
0.8 1
1.2
1.4
1.6
1.8 2
2.2
Median of Neo intimal area (mm2)
Percent of lesions (%)
Orsiro
Xience Prime
Mean value
1.00± mm2
0.74± mm2
Orsiro
Xience Prime P
Well-apposed struts
98.6%
98.8%
0.62
Incomplete Strut Apposition
1.0%
0.6%
0.32
Non-apposed side branch
0.4%
0.37
Covered Struts
98.3%
97.5%
0.042
P=0.024

22. Δ Neointimal hyperplasia
IVUS 9 Months
Stent apposition by IVUS @ 9-month FUP was % in both study arms
Δ Mean lumen area
@ 9 M FUP
Δ Neointimal hyperplasia
mm2
P = 0.34
P = 0.043
Lesions
N = 31
N = 25

23. Limitations
BIOFLOW-II included patients with relatively simple clinical and angiographic characteristics
Patients with AMI, CTO, bifurcation, ostial, SVG, unprotected LM, severely calcified lesions, or lesions with thrombus were excluded
BIOFLOW-II was not powered to detect differences in clinical event rates
However, an all-comer RCT powered for clinical endpoints directly comparing Orsiro and Xience has completed enrollment

24. Conclusions
In this prospective, multicenter, randomized controlled trial the ORSIRO sirolimus-eluting stent with a biodegradable polymer was non-inferior to the XIENCE Prime everolimus-eluting stent with durable polymer for the primary angiographic endpoint of in-stent late loss at 9 months
Clinical event rates were low and comparable with both ORSIRO and XIENCE Prime through 9 months
These results will need to be extended to larger randomized trials powered for clinical endpoints including more complex patients