Carlo Di Mario, Nicolas Foin

Biolimus-A9™ Eluting Biomatrix Stent

Biolimus is a semi-synthetic sirolimus analogue with 10x higher lipophilicity and similar potency as sirolimus.

Biolimus is immersed into a biodegradable polymer, polylactic acid, and applied solely to the abluminal stent surface

Biolimus is co-released with polylactic acid that completely desolves into carbon dioxide and water after a 6-9 months period.

The same coating and drug has been successfully used in bifurcational trials with the dedicated self-expanding DEVAX platform

The stainless steel stent platform has a strut thickness of 120 µm with a quadrature link design.

Maximum cell circumference*

(mm)

10.8

9.5

19.8

12.6

12.6

Maximum cell diameter*

(mm)

3.7

3.0

6.3

4.0

4.0

Stent Cell Size*Based on 3mm stent

Distal LCX:A=8.54smm; MD=3.41mm

Proximal LCxA=12.99smm; MD=4.14mm

3.0x28 & 4.0x8 Biomatrix Flex + KB 3.0/3.0

StJude FD-OCTfrom Dist LCx@ 2 cm/sec

Micro-CT

B

45º

3.5 mm2.5 mm

2.5 mm

A

Biomatrix Flex after KB

Micro-CT Flow Chart

A

B

C

3.0 MV, 2.5 SB at 12 ATMMicro-CT Biomatrix Flex Results

Biomatrix Flex Xience

Biomatrix Flex Xience

AFTER

KISSING

MV

STENT

N.Foin/C. Di Mario

Patient groups 850 patients

No Bifurcation 611Bifurcation 239

Technique Type 1-stent 197 True 992-stent 42 Partial 140

Lesion groups 1213 lesions

No Bifurcation 961Bifurcation 252

True, 1-stent technique 75True, 2-stent technique 27Partial, 1-stent technique 135Partial, 2-stent technique 15

Patient groups 857 patients

No Bifurcation 599Bifurcation 258

Technique Type1-stent 204 True 1242-stent 54 Partial 134

Lesion groups 1254 lesions

No Bifurcation 972Bifurcation 282

True, 1-stent technique 94True, 2-stent technique 37Partial, 1-stent technique 129 Partial, 2-stent technique 22

• Procedural data was collected on bifurcation technique by reviewing the angiogram of each bifurcation lesion (Dr Scot Garg)

Final Analysis497 patients534 lesions

LEADERS Trial (Windecker, Serruys)•Multicentre (n=10) • Non-inferiority • Allcomers

2,467 lesions in 1,707 patientsRandomisedSES BES

True bifurcation: Medina 1,1,1; 1,0,1; 0,1,1 Partial bifurcation: Medina 1,0,0; 1,1,0; 0,1,0; 0,0,1

28.1% Pts have at least 1 Bifurc.

20.1% Lesions are bifurcations

30.1% Pts have at least 1 Bifurc.

22.4% Lesions are bifurcations

Treated Bifurcation Lesions534 lesions/497 patients

True bifurcations*233 lesions

Partial bifurcations301 lesions

Two wires 174 lesions

One wire 59 lesions

2-stent technique64 lesionsClassic T 30Crush 23Culotte 7Modified T 1 V stenting 3

1-stent technique169 lesions

Post stenting dilatation49 lesions

Kissing balloon 43

Two wires 229 lesions

One wire 72 lesions

One stent technique264 lesions

2-stent technique37 lesions

Cross-over 9Classic T 16Crush 7Culotte 1Modified T 2V stenting 2

Post stenting dilatation73 lesions

Kissing balloon 37

Post stenting dilatation15 lesions

Kissing balloon 12

Post stenting dilatation95 lesions

Kissing balloon 38

*Includes 8 trifurcation lesions

27.4% 72.6% 12.3% 87.7%

67.2% 21.9% 32.4% 14.4%

True bifurcation: Medina 1,1,1; 1,0,1; 0,1,1 Partial bifurcation: Medina 1,0,0; 1,1,0; 0,1,0; 0,0,1

Demographic and Angiographic CharacteristicsBifurcation

Lesion (n=497)Non-bifurcation lesion (n=1210) P value

Age (years) 64.7 64.6 NSMale (%) 72.6 75.7 NSPrevious MI (%) 37.2 30.4 0.007Diabetes (%) 21.7 25.3 NSCurrent smoker (%) 20.5 26.3 0.011Hypertension (%) 72.8 73.2 NSHypercholesterolaemia (%) 68.0 66.3 NSACS (%) 53.9 55.8 NSSYNTAX Score 16.8 12.0

Stent Thrombosis @ 12 Mths

Stent Thrombosis (%) Bifurcation Group

(n=497)

Non-Bifurcation

Group(n=1210)

P Value

Stent thrombosis (%) 4.0 3.0 NSDefinite 2.2 1.9 NSProbable 0.6 0.5 NSPossible 1.2 0.8 NS

True vs. Partialp=NSStent Thrombosis

1-stent vs. 2-stent

Bifurcation Outcome @ 12 Months

Bifurcation Group(n=497)

Non-Bifurcation

Group(n=1210)

P Value

Death (%) 3.2 3.2 NSCardiac Death (%) 2.8 2.2 NSMyocardial Infarction (%) 7.2 4.3

Clinically Justified TVR @ 24 Mths

Bifurcation Group BES vs. SES

HR 0-2 days : 0.62 [0.10-3.77] p=0.603-360 days : 0.33 [0.16-0.72] p=0.005

Sirolimus Bifurcation groupBiolimus Bifurcation groupSirolimus Non-bifurcation groupBiolimus Non-bifurcation group Garg et, EuroIntervention 2009

Number at risk

BES 258 255 242 237 231 225 214SES 239 237 212 206 201 194 180

11.5%

4.3%

Δ7.2%

Clinically-Indicated TVR @ 3 Years Bifurcations

Months

13.2%

6.8%

Δ6.4%

BESSES

*P values for superiority

0 6 12 18 24 3630

%

5

10

15

20

16.0%

8.9%

3-year HR0.53 [0.31 to 0.89]

P = 0.015*

Δ7.1%

2-year HR0.49 [0.27 to 0.89]

P = 0.018*

1-year HR0.37 [0.18 to 0.74]

P= 0.005*

0 6 12 18 24 30 36

From Windecker et al, TCT 2010

Definite ST Bifurcations

1.0

2.0

3.0%

1.9%

4.3%

BESSES

*P values for superiority

0 6 12 18 24 3630Months

1.9%

3.8%2.5%

1.9%

3-year HR0.46 [0.16 to 1.35]

P = 0.15*

0

4.0

Number at risk

BES 258 255 245 242 239 236 226

SES 239 237 226 226 224 215 202

Δ 0.6%Δ 1.9%

Δ 2.4%

5.0

6.0 2-year HR0.52 [0.17 to 1.54]P = 0.23*

1-year HR0.77 [0.24 to 2.52]P = 0.67*

0 6 12 18 24 30 36

From Windecker et al, TCT 2010

Biomatrix in BifurcationsConclusions

The Biomatrix Flex stent offers a large opening

when dilated through the struts, sufficient to fit

almost all coronary anatomies

Biolimus eluting stent appears to offer an advantage

in treating patients with bifurcational lesions

Larger cohorts of prospectively collected data as

well as mechanistic insights are needed to confirm

these findings.

Cardiac Death Bifurcations

Months

%

2.9%

2.7%Δ0.2% 3.5%

3.8%

Δ0.3%

5

10

20BESSES

*P values for superiority

Number at risk

BES 258 257 251 247 244 241 229SES 239 239 231 231 231 224 210

0 6 12 18 24 3630

3.9%

5.5%

3-year HR0.71 [0.31 to 1.63]

P = 0.42*

Δ1.6%

15

2-year HR0.93 [0.37 to 2.34]

P = 0.88*

1-year HR0.92 [0.32 to 2.63]

P = 0.88*

All MI Bifurcations

5

10

20

% 9.8%

9.1%

BESSES

*P values for superiority

0 6 12 18 24 3630Months

15

Number at risk

BES 258 256 229 226 224 220 212

SES 239 237 219 219 217 210 195

9.0%

5.5%

3-year HR1.13 [0.63 to 2.01]

P = 0.69*

Δ0.7%Δ3.5%

6.8%

9.4%

Δ2.6%

2-year HR1.42 [0.75 to 2.67]

P = 0.28*

1-year HR1.67 [0.85 to 3.30]

P = 0.14*

A

B

C

A

B

C

Micro-CT KB

Final Proximal Correction A

B

C

DD

A

B

C

D

N. Foin, G.Secco, R.Krams and C. Di Mario, submitted 2010

Final Proximal Correction

N. Foin, G.Secco, R.Krams and C. Di Mario, submitted 2010

Azertyuiop Qsdfghjklm

• Azertyuiop– Qsdfghjklm– Wxcvbn

• Qsdfghjklm– Azertyuiop– Wxcvbn

Bifurcation Results (3)

Outcome (12 months)One stent technique BES SES(n=204) (n=197)

P Value

Death (%) 3.9 2.5 NS

Cardiac Death (%) 3.4 2.5 NS

Myocardial Infarction (%) 7.8 5.6 NS

All TLR(%) 4.9 11.7

Bifurcation Results (2)

Outcome (12 months)Bifurcation GroupBES SES(n=258) (n=239)

P Value

Death (%) 3.5 2.9 NSCardiac Death (%) 2.7 2.9 NSMyocardial Infarction (%) 8.9 5.4 NSAll TLR(%) 4.7 12.1

Myocardial Infarction

Bifurcation Group BES vs. SES

HR 0-2 days : 2.54 [1.07-6.05] p=0.033-360 days : 0.64 [0.18-2.27] p=0.49

Sirolimus Bifurcation groupBiolimus Bifurcation groupSirolimus Non-bifurcation groupBiolimus Non-bifurcation group

Myocardial infarction

No clear explanation

BES similar thrombogenicity to

BMS

Polymer does not degrade until>6

months

Pre-dilatation was significantly higher in MI group treated

with BES (88% vs. 44%, p=0.03)

No effect on death/cardiac death

>90% peri-procedural MIs, defined on basis of raised cardiac enzymes

Carlo Di Mario, Nicolas FoinBiolimus-A9™ Eluting Biomatrix StentDiapositive numéro 3Diapositive numéro 4Micro-CTDiapositive numéro 6Diapositive numéro 73.0 MV, 2.5 SB at 12 ATM�Diapositive numéro 9Diapositive numéro 10Demographic and Angiographic CharacteristicsStent Thrombosis @ 12 MthsBifurcation Outcome @ 12 MonthsClinically Justified TVR @ 24 MthsClinically-Indicated TVR @ 3 Years �BifurcationsDefinite ST �BifurcationsBiomatrix in Bifurcations� Conclusions Cardiac Death �Bifurcations�All MI �BifurcationsDiapositive numéro 20Diapositive numéro 21Diapositive numéro 22Azertyuiop QsdfghjklmBifurcation Results (3)Bifurcation Results (2)Myocardial InfarctionMyocardial infarction