1. University Hospital of Caen ClinicalTrials.gov Identifier: NCT01214148
First-in-man experience with the DES Orsiro in the treatment of patients with single de novo coronary artery lesions (BIOFLOW-I)
Martial Hamon, MD, FESC
University Hospital of Caen
Normandy, France
ClinicalTrials.gov Identifier: NCT

2. Potential conflicts of interest
Speaker’s name: Martial Hamon
 I have the following potential conflicts of interest to report:
 Research contracts  Consulting for BIOTRONIK AG
 Employment in industry
 Stockholder of a healthcare company
 Owner of a healthcare company
 Other(s)
 I do not have any potential conflict of interest 2

3. Background
Early generations of DES have reduced restenosis, but have been associated with an increased risk of late events
Efforts to resolve these problems have been made including improvements in stent platforms, polymer carriers as well as drug selection
A hybrid combination of active and passive coatings on a DES aim to optimize effectiveness of results and also mediate the threat of late events
The aim of the BIOFLOW-I study was to evaluate the safety and efficacy of the Orsiro Hybrid Drug Eluting Stent with a bioabsorbable polymer, in patients with a single de novo lesion in a native coronary artery
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4. The device: Orsiro Hybrid Drug Eluting Stent
PROBIO® passive coating encapsulates the stent and minimizes interaction between the metal stent and the surrounding tissue
BIOlute® active coating contains a highly biocompatible polymer which delivers a Limus drug via a biodegradable matrix
PRO-Kinetic Energy Stent System brings good deliverability for reaching complex lesions
BIOlute® achieves a
controlled drug release
Quick facts
Passive coating
PROBIO® amorphous silicon carbide coating
Active coating
BIOlute® bioabsorbable PLLA eluting Sirolimus
Drug dose
1.4 µg/mm2
Stent material
Cobalt chromium L-605
Strut thickness
60 µm (3.00 mm stent)
Approval status
CE approved
The BIOlute® polymer matrix gently degrades into CO2 and H2O
Only a PROBIO® sealed stent is left in the arterial wall

5. Investigational centers & core lab
Principal investigator
Rodica Niculescu, MD, PhD, FESC
Spitalul Clinic de Urgenţă Bucureşti, Romania
15 Subjects enrolled
100% Angio & IVUS 4month
100% Angio & IVUS 9month
Angiography Corelab
Ron Waksman MD
MedStar Health Research Institute, Washington DC, USA
Principal investigator
Dan Deleanu, MD, FESC
Institutul de Urgenţă pentru Boli Cardiovasculare, Romania
15 Subjects enrolled
100% Angio 4month
100% Angio 9month
IVUS Corelab
Neil J. Weissman MD
MedStar Health Research Institute, Washington DC, USA
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6. BIOFLOW-I trial design
Design: Prospective, multi-centre, first in man trial
Patient Number: 30
Patents with angiographic follow-up: 30
Patients with IVUS follow-up: 15
Follow-up rate: 100%
Enrollment time: Between 02 – 23 July 2009
Clinical endpoint assessment
30 d
4 mo
9 mo
12 mo
2 yr
3 yr
Angiographic & IVUS endpoint assessment

7. Study endpoints Primary Endpoint Secondary Endpoints Definitions
In-stent late lumen loss at 9 months by QCA
Secondary Endpoints 
In-stent and in-segment binary restenosis rate at 4 and 9 months post procedure
Clinically driven target lesion revascularization (TLR) at 1, 4 and 9 months and at 1, 2 and 3 years post-procedure
Composite of cardiac death, MI attributed to the target vessel and clinically driven target lesion revascularization at 1, 4 and 9 month post-procedure, and yearly up to 3 years
Stent thrombosis at 1, 4 and 9 months, and at 1, 2 and 3 years post-procedure.
Definitions
Lesion Treatment Success is defined as the attainment of <30% residual stenosis by offline QCA using any percutaneous method
Device Success defined as achievement of a final residual diameter stenosis of <30% by offline QCA, using the assigned device only

8. Patient eligibility Exclusion Criteria Inclusion Criteria
Patient is ≥18 years old
Clinical evidence of ischemic heart disease and / or a positive functional study. Documented stable angina pectoris, or documented silent ischemia
Single de novo lesion with ≥50% and <90% stenosis in 1 coronary artery
Exclusion Criteria
Documented left ventricular ejection fraction (LVEF) ≤ 30%
ACS (NSTE-MI or STEMI)
Three-vessel coronary artery disease
Evidence of myocardial infarction within 72 hours prior to the index procedure
Total occlusion (TIMI 0 or 1)
Target lesion is located in or supplied by an arterial or venous bypass graft
Target lesion involves a side branch >2.0mm in diameter
Unprotected Left main coronary artery disease (stenosis >50%)

9. Baseline clinical characteristics
Age, years
58.10 yrs ± 9.80
Male sex
60.0%
18/30
Hyperlipidemia
93.3%
28/30
History of MI
73.3%
22/30
Hypertension
66.6%
20/30
Smoker
53.3%
16/30
Diabetes
23.3%
7/30
CHF
20.0%
6/30

10. Baseline lesion characteristics
Pre-Procedure
N=30
RVD (mm)
2.75 ± 0.34
MLD (mm)
0.95 ± 0.29
% Diameter stenosis
65.52 ± 9.47
Mean Lesion length (mm)
11.71 ± 4.40
Procedural
Stent length per lesion (mm)
19.93 ± 5.33
Stent diameter per lesion (mm)
3.08 ± 0.37
Direct stenting
20.0%
Device success*
100.0%
* Defined as In-Stent < 30% residual stenosis by offline QCA

11. Angiographic follow-up results
4-month FUP
9-month FUP
RVD (mm)
2.81 ± 0.28
2.81 ± 0.30
Minimal Lumen Diameter
In-stent (mm)
2.50 ± 0.36
2.56 ± 0.38
In-segment (mm)
2.20 ± 0.35
2.21 ± 0.31
Diameter Stenosis
In-stent (%)
15.19 ± 4.55
13.60 ± 4.27
In-segment (%)
23.66 ± 9.80
23.55 ± 8.06
Late Loss
0.12 ± 0.19
0.05 ± 0.22
0.06 ± 0.23
0.05 ± 0.26
Binary Restenosis 0%

12. Cumulative frequency of Diameter Stenosis
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13. Cumulative Frequency of Minimum Lumen Diameter
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14. Cumulative Frequency of In-Stent Late Lumen Loss
Mean In-Stent LLL:
4 Months ± 0.21
9 Months ± 0.22
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15. IVUS results Mean net volume obstruction: 0.00% @ 4 months

16. Clinical outcomes at 9 months
9-month clinical results N %
Death
0.0
Stent thrombosis MI
TLR (clinically driven) 2
6.7
MACE 16

17. BIOFLOW-I results in perspective
Overview of in stent late lumen loss in FIM trials
FIM SR3
4 m
n=15
Nevo
Nevo Res-I2*
6 m
n=186
XienceV
SPIRIT First1
n=28
Endeavor Resolute
Orsiro
BIOFLOW-I
9 m
n=30
FIM FR3
FIM4
FIM5
n=92
Cypher
± 0.21
± 0.31
± 0.30
± 0.26
± 0.27
± 0.22
(mm)
0.10
0.13
0.09
-0.01
0.12
0.22
0.05
* Randomized trial. Only number of patients in device arm displayed
1 Serruys et al. A randomized comparison of a durable polymer Everolimus-eluting stent with a bare metal coronary stent: The SPIRIT first trial; Eurointervention
2 Ormiston et al. Six-month results of the NEVO Res-Elution I (NEVO RES-I) trial: a randomized, multicenter comparison of the NEVO sirolimus-eluting coronary stent with the TAXUS Liberte paclitaxel-eluting stent in de novo native coronary artery lesions; Circ.Cardiovasc.Interv.
3 Sousa et al. Lack of neointimal proliferation after implantation of sirolimus-coated stents in human coronary arteries: a quantitative coronary angiography and three-dimensional intravascular ultrasound study; Circulation
4 Meredith et al. The next-generation Endeavor Resolute stent: 4-month clinical and angiographic results from the Endeavor Resolute first-in-man trial; EuroIntervention
5 Meredith et al. Clinical and angiographic results with the next-generation resolute stent system: a prospective, multicenter, first-in-human trial; JACC.Cardiovasc.Interv.

18. Pre-procedural angiography
BIOFLOW-I Case report
Pre-procedural angiography
Medical history & risk factors
Male, 53 yrs
MI (April-2009), smoker, hyperlipidemia, DM (insulin)
Procedure 09 JUL 2009
RCA mid
Lesion length 16 mm
Source: BIOFLOW-i case, patient ROM
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19. Post-procedural angiography
BIOFLOW-I Case report
Post-procedural angiography
Medical history & risk factors
Male, 53 yrs
MI (April-2009), smoker, hyperlipidemia, DM (insulin)
Procedure 09 JUL 2009
RCA mid
Lesion length 16 mm
Post-dilatation
Stent size 3.5 x 18 mm
Max pressure 21 atm
Source: BIOFLOW-i case, patient ROM
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20. Four-month follow-up angiography
BIOFLOW-I Case report
Four-month follow-up angiography
Medical history & risk factors
Male, 53 yrs
MI (April-2009), smoker, hyperlipidemia, DM (insulin)
Procedure 09 JUL 2009
RCA mid
Lesion length 16 mm
Post-dilatation
Stent size 3.5 x 18 mm
Max pressure 21 atm
Source: BIOFLOW-i case, patient ROM
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21. Nine-month follow-up angiography
BIOFLOW-I Case report
Nine-month follow-up angiography
Medical history & risk factors
Male, 53 yrs
MI (April-2009), smoker, hyperlipidemia, DM (insulin)
Procedure 09 JUL 2009
RCA mid
Lesion length 16 mm
Post-dilatation
Stent size 3.5 x 18 mm
Max pressure 21 atm
Source: BIOFLOW-i case, patient ROM
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22. BIOFLOW Clinical Program for Orsiro Hybrid Drug Eluting Stent
A prospective, multi-centre, single treatment clinical trial
Endpoint: LLL 9 months, N=30
A prospective, multi-center, non-inferiority, randomized study, Orsiro vs. Xience Prime
Endpoint: LLL at 9 months, N=440
Study design
Clinical strategy
First-in-man study evaluating safety and efficacy, data submitted during CE approval (TÜV)
Comparative, non-inferiority trial evaluating safety and efficacy
A prospective, multi-centre, single treatment clinical study
Endpoint: LLL at 9 months, N=120
A prospective, multi-centre, single treatment clinical registry
Endpoint: TLF at 9 months, with long term follow-up, N=1000+
Study design
Clinical strategy
Study to evaluate safety and efficacy in a complex patient population
Post marketing surveillance to demonstrate long term outcomes

23. Conclusions
In this FIM study with a primary angiographic endpoint, the Orsiro Hybrid DES showed excellent results in terms of late lumen loss in the overall patient population
This mixed population of patients is atypical for a FIM study, with its high rate of diabetic patients and complex lesions
At 9 months follow-up, no late catch-up was seen in the LLL values and a narrow standard deviation suggests that these study results are quite robust
A larger randomized, comparative study is currently running to prove the safety and effectiveness of this promising device