le stent biobasorbable bernard chevalier icps massy / gcs creil

Le stent biobasorbable

Bernard Chevalier

ICPS Massy / GCS Creil

© 2009 Abbott Laboratories Pipeline product. Currently in development at Abbott Vascular. Not available for sale.

• In the last five years , I received research grants or speaker fees or I am/was consultant for: Abbott Vascular, Asahi, Astra Zeneca, AVI, Boston Scientific, Biotronik, Colibri, Cook, Cordis, Daichi-Sankyo, Eli-Lilly, Iroko, Medtronic, Terumo. I am currently minor shareholder & general mamager of CERC


Limitations des stents permanents


• Conformabilité (R)

• Echapement (R)

• Malapposition (T)

• Retard de cicatrisation (T)

• Elution permanente de drogue (T)

• « Jailing » des branches

• Interference MSCT


Atheroprogression

• Zones de low shear stress (mailles)

• Alteration vasomotricité

• Alteration fonction endotheliale

• Alteration adaptation diamètre au stress V

• Conformabilité


Bioabsorbable concept:BVS « SCAFFOLD »


What is the Minimum Duration of Radial Scaffolding?

Serruys PW, et al., Circulation 1988; 77: 361.

n = 342 patients (n = 93 at 30-day F/U; n = 79 at 60-day F/U; n = 82 at 90-day F/U; n = 88 at 120-day F/U)

The lumen appears to stabilize approximately three months after PTCA.

p < 0.00001

p < 0.00001

Quantitative angiographic study in 342 consecutive patients at 1, 2, 3, and 4 months


Poly Lactide - Hydrolysis

LactideLactide

PLAPLAPLAPLA

Molecular Weight Molecular Weight

H2O

Hydrolysis

Mass LossMass Loss

Krebs Krebs CycleCycleKrebs Krebs CycleCycle

Mass TransportMass Transport

CO2 + H2O

RO

R′OH2O+ R

OR′

OHHO+

carboxylic acid alcohol

PLA – Poly Lactic Acid


Bioresorbable Polymer: ABSORB

• Everolimus/PDLLA Matrix Coating

• Thin coating layer• Amorphous (non-crystalline)• 1:1 ratio of Everolimus/PLA

matrix• Conformal Coating, 2-4 m

thick• Controlled drug release

• PLLA Backbone• Highly crystalline• Provides device integrity• Processed for increased radial

strength

Polymer backbone

Drug/polymer matrix


ABSORB Cohort A: 5-year clinical results

Hierarchical6 Months

30 Patients12 Months

29 Patients**24 Months

29 Patients**60 Months

29 Patients**

Ischemia Driven MACE*** 1 (3.3%)* 1 (3.4%)* 1 (3.4%)* 1 (3.4%)*

Cardiac Death 0 (0.0%) 0 (0.0%) 0 (0.0%) 0 (0.0%)

MI 1 (3.3%)* 1 (3.4%)* 1 (3.4%)* 1 (3.4%)*

Q-Wave MI 0 (0.0%) 0 (0.0%) 0 (0.0%) 0 (0.0%)

Non Q-Wave MI 1 (3.3%)* 1 (3.4%)* 1 (3.4%)* 1 (3.4%)*

Ischemia Driven TLR 0 (0.0%) 0 (0.0%) 0 (0.0%) 0 (0.0%)

by PCI 0 (0.0%) 0 (0.0%) 0 (0.0%) 0 (0.%)

by CABG 0 (0.0%) 0 (0.0%) 0 (0.0%) 0 (0.%)

* Same patient – this patient also underwent a TLR, not qualified as ID-TLR (DS = 42%)** One patient missed the 9, 12, 18 month and 2, 3, and 4 year visits; one patient died from a non-cardiac cause 706 days post procedure*** MACE – Composite endpoint comprised of cardiac death, myocardial infarction (MI) and ischemia-driven target lesion revascularization (TLR) by PCI or CABG

Serruys, PW, TCT, 2011


ABSORB Vasomotor Function Testing

Serruys, PW, et al. Lancet 2009; 373: 897-910.

The reappearance of vasomotion in the proximal, distal, as well as treated segments in response to methergin or acetylcholine suggests that vessel vasoreactivity has been restored and that a physiological response to vasoactive stimulus might occur anew.


BVS Device Optimization Objectives

Cohort A

Cohort B Photos taken by and on file at Abbott Vascular.

More uniform strut distribution

Higher radial strength

Storage at room temperature

Improved device retention

Unchanged:• Material, coating and backbone• Strut thickness• Drug release profile• Total degradation Time


Study Design of ABSORB Cohort B

• Sponsor: Abbott Vascular

• Primary Investigators:

– PW Serruys MD, PhD

– J Ormiston MD

• DSMB: J Tijssen PhD, M Wiemer MD, P Urban MD

• CEC: C Hanet MD, R Tölg MD, V Umans MD

• Angiographic, IVUS and OCT Corelab: Cardialysis

• Prospective, open label, FIM

• 3.0 x 18mm devices to treat up to 2 lesions ≤ 14mm in length

12 sites Europe, Australia, New Zealand

• B de Bruyne, MD• D Dudek, MD• L Thuesen, MD• P Smits, MD• B Chevalier, MD• D McClean, MD• J Koolen, MD• S Windecker, MD• R Whitbourn, MD• I Meredith, MD, PhD

• 101 patients enrolled between 19 March and 6 November 2009

QCA, IVUS, OCT, IVUS VH

Group B1 (n = 45)

Baseline 6 12 24MonthsMonthsMonths

Group B2 (n = 56)


Late Lumen Loss is Similar to XIENCE V Through 2 Years

Cumulative Late Loss curves of ABSORB Cohort B and Xience V



Minimal LD 1.58 mmMean LD 2.12 mm

MLD 2.46 mmMean LD 2.72mm Mean LD

∆-0.6mm(-22%)

Minimal LD 2.32 mmMean LD 2.67 mm

Mean LD∆+0.55mm(+26%)

Preprocedure

FUP before vasomotion 5 Min. After Methergine After Nitro

Post procedure

QCA post procedure

MLD 2.45mm

Late Loss: -0.01mm

Serruys, PW. ACC 2011Serruys, PW. ACC 2011

Mean LD∆-0.6mm(-22%)

Mean LD∆+0.55mm

(+26%)

SE2935049 Rev. B Information contained herein intended for healthcare professionals from outside the US only.


91° 88°128°

© 2009 Abbott Laboratories Pipeline product. Currently in development at Abbott Vascular. Not available for sale.MACE: Cardiac death, MI, ischemia-driven TLRTVF: Cardiac death, MI, ischemia-driven TLR, ischemia-driven TVR

No scaffold thrombosis by ARC or Protocol

30 Days 6 Months 9 Months 12 Months

N = 101 N = 101 N = 101 N = 101

Cardiac death (%) 0 0 0 0

Myocardial Infarction % (n) 2.0 (2) 3.0 (3) 3.0 (3) 3.0 (3)

Q-wave MI 0 0 0 0

Non Q-wave MI 2.0 (2) 3.0 (3) 3.0 (3) 3.0 (3)

Ischemia driven TLR % (n) 0 2.0 (2) 2.0 (2) 4.0 (4)

CABG 0 0 0 0

PCI 0 2.0 (2) 2.0 (2) 4.0 (4)

Hierarchical MACE % (n) 2.0 (2) 5.0 (5) 5.0 (5) 6.9 (7)

Hierarchical TVF % (n) 2.0 (2) 5.0 (5) 5.0 (5) 6.9 (7)

ABSORB Cohort B, Group 1&2Clinical Results - Intent to treat


6.9%

7.5%

0.6%

393-day HR0.93 [0.38,2.24]

p=0.8678

BVS(B1+B2)XV(SPI+SPII+SPIII RCT)

MA

CE

(C

-Death

, MI, ID

-TLR

)

0.0%

5.0%

10.0%

15.0%

20.0%

25.0%

Time Post Index Procedure (Months)

0 1 2 3 4 5 6 7 8 9 10 11 12 13 14

6.9%

7.5%

0.6%

393-day HR0.93 [0.38,2.24]

p=0.8678

BVS(B1+B2)XV(SPI+SPII+SPIII RCT)

MA

CE

(C

-Death

, MI, ID

-TLR

)

0.0%

5.0%

10.0%

15.0%

20.0%

25.0%

Time Post Index Procedure (Months)

0 1 2 3 4 5 6 7 8 9 10 11 12 13 14

XV Includes only patients with single 3.0 x 18mm stent

BVS Includes all patients

MACE rate in Pts treated with BVS (Cohort B, n=101) vs. a single 3x 18 mm EES (Spirit I+II+III, n=227)


BL 2Y6M

Resolved ISA Non Discernible

Persistent ISA

ISA incomplete stent appositionISA incomplete stent apposition

Lateacquired ISA

Resolved ISA Non Discernible

ApposedApposed

Bioresorption and vessel wall integration are a reality.

Serruys, PW, PCR, 2010


Bioresorption at jailed side branch is a real phenomenon

Okamura et al., EHJ, 2010


First 200 Pts ABSORB EXTEND Follow-up

* Patient was treated with a metallic DES, not ABSORB

Abizaid, A., TCT, 2011

30 Days 6 Months

Non-hierarchical N = 200 N = 200

Cardiac Death % (n) 0 0.5 (1)*

Myocardial Infarction % (n) 2.0 (4) 2.0 (4)

Q-wave MI 1.0 (2) 1.0 (2)

Non Q-wave MI 1.0 (2) 1.0 (2)

Ischemia driven TLR % (n) 0.5 (1) 0.5 (1)

CABG 0 0

PCI 0.5 (1) 0.5 (1)

Hierarchical MACE % (n) 2.0 (4) 2.5 (5)

Hierarchical TVF % (n) 2.0 (4) 3.0 (6)**

** One additional ischemia driven non-TL TVR treated by CABG


BVS size usage with vessel dimensions

Target Vessel Diameter Distal Dmax and Proximal Dmax

Target Lesion(s) Length

BVS Size To Be Used

14 mm Single 2.5 x 18 mm

> 14 mm and 22 mm Single 2.5 x 28 mm ≥ 2.0 mm and 3.0 mm

> 22 mm and 28 mm Two overlapping 2.5 x 18 mm

14 mm Single 3.0 x 18 mm

> 14 mm and 22 mm Single 3.0 x 28 mm ≥ 2.5 mm and 3.3 mm

> 22 mm and 28 mm Two overlapping 3.0 x 18 mm

≥ 2.0 mm and 2.5 mm (Distal Dmax)

≥ 3.0 mm and 3.3 mm

(Proximal Dmax)

> 22 mm and 28 mm Overlapping 2.5 x 18 with 3.0 x 18 mm

Post dilatation with NC balloon < 2.75 mmPost dilatation with NC balloon < 2.75 mm

Post dilatation with NC balloon < 3.25 mmPost dilatation with NC balloon < 3.25 mm

DREAMS provides scaffolding and paclitaxel release up to 3 months

Mg alloy

Initial Mg degradationStable drug carrier layerControlled drug release

Mg degradation completedDrug release completedDegradation of polymer ongoing

Conversion of degradation product completedDrug carrier layer degradation completedBeginning of structural disintegration

Mg degradation product

Polymer

acute 3 months 6 months 9 months

Mg Mg

ScaffoldingPaclitaxel release

Mg + 2H2O Mg(OH)2 + H2

Soft Hydroxyapatite

Biodegradation

Bioabsorption

BIOSOLVE-I 6-month IVUS** Results

Contribution to lumen loss

Post implantation

Loss of scaffolding area

In-stentneointima

6-month Follow-upScaffoldDegradation

0.35 mm 0.33 mm0.68 mm LLL

0.57 mm 0.51 mm1.08 mm LLL

39% less 35% less37% less

53% 47%

* Erbel R. et al., Lancet 2007;369:1869-75, Waksman et.al, JACC 2009, 312-320** N= 12 evaluable IVUS runs (volumetric) available at 6-month follow-up for cohort 1

PROGRESS

BIOSOLVE-I


L’absorption complète est confirméeLes résultats sont équivalents aux DES récents

Grâce à un processus lent Lésions plus complexes Le temps de la comparaison randomisée est venu (Absorb

II)Des effets spécifiques sur la cicatrisation artérielle

Vasomotricité, conformabilité, remodelage positif, pas de stimulus pour la néoathérogénèse

Possibles bénéfices à long termeDébut d’un long programme clinique

Mais mise sur le marché en 2012 !?!

Conclusion

le stent biobasorbable bernard chevalier icps massy / gcs creil

Documents

abbott vascular

patients n

day fu n

bvs scaffold slide

consecutive patients

everolimuspdlla matrix

drogue t

qwave mi1