LE STENT BIO RESORBABLE VA-T-IL

DEVENIR LE GOLD STANDARD?

R KONING ST HILAIRE-ROUEN

B

Bioresorbable Vascular Scaffold (BVS): Ideal of Leaving Nothing Behind

Short Term Long Term

Data and images on file at Abbott Vascular. Histology images are from porcine animal models. 3ème Révolution Technologique ! PWS

Iqbal,…..Serruys, EHJ march 2014

• The cumulative incidence of late TLR beyond 4 years after balloon angioplasty (BA) tended to be lower than that after bare

metal stent (BMS) implantation

Yamaji K, et al. J Am Heart Assoc 2012;1:e004085 doi:10.1161/JAHA. 112.004085.

Long-term Balloon Angioplasty TLR rate

Impact of Late Disease Progression Following Balloon Angioplasty

BA: ~1.0 % per year after 4 years

BMS: ~1.6 % per year after 4 years

Survival Event Free Survival

Impact of Endothelial Dysfunction on Long-Term Clinical Outcomes

Normal endothelial function is associated with improved survival and event-free survival compared with endothelial dysfunction.

Deanfield, J. et al. Circulation. 2007; 115: 1285-1295.

Preliminary Evidence of Vasomotion Suggests Improved Long-term Outcomes

∆ in

Ves

sel D

iam

eter

(mm

)

Methergine

Acetylcholine

-1

-0.5

0

0.5

1

(N=15)

6 Months1

(N=6) (N=19)

12 Months2

(N=13) (N=9)

24 Months3

(N=7)

Vaso

dila

tion

Va

soco

nstr

icti

on

ABSORB Cohort B1 ABSORB Cohort B2 ABSORB Cohort A

(pre

-dru

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fusi

on to

pos

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ug in

fusi

on)

1. Data on file at Abbott Vascular/ 2. Adapted from Serruys, PW. et al. J Am Coll Cardiol. 2011; 58: 1578-88./ 3. Adapted from Serruys, PW, et al. Lancet 2009; 373: 897-910.

Total Pts Studied n=~599 n~965 n~5,709 n~7,609 n~8,709 n~9,709

2011 2012 2013 2014 2015 2016

ABSORB Japan n = ~400, Japan Pivotal RCT

Enrollment & Follow-Up 2 Y 1 Y

ABSORB China n = ~440, China Pivotal RCT

Enrollment & Follow-Up 2 Y 1 Y

ABSORB II n = ~501, International RCT

2 Y 3 Y 1 Y Enrollment & Follow-Up

ABSORB EXTEND n = ~800, Registry

1 Y Enrollment & Follow-Up

ABSORB Cohort B n = 101; FIM

1 Y 2 Y 3 Y 4 Y 5 Y

ABSORB Cohort A n = 30; FIM

5 Y

ABSORB FIRST n = ~1,800, International Registry

Enrollment & Follow-Up 1 Y

Each trial n reflects total patients. Data effective June 2014 *ABSORB IV trial is in the planning stage and subject to change.

ABSORB III n = ~2,250, US Pivotal RCT

Enrollment & Follow-Up 1 Y 2 Y

ABSORB IV* n = ~3,000, US RCT

UK Registry n = 1000, UK Registry

Enrollment & Follow-Up 1 Y

Absorb Comprehensive AV-Sponsored Clinical Program: >10,000pts

2 Y

Absorb n = 335

XIENCE PRIME n = 166

Prospective, Multi-Center, Randomized Clinical Trial 2:1 Randomization Absorb versus XIENCE PRIME

n =501 patients

Absorb Clinical Update ABSORB II – Trial Design

Device Sizes

Treatment

Co-primary Endpoints

• Vasomotion assessed by change in Mean Lumen Diameter between pre- and post-nitrate at 3 years (superiority)

• Minimum Lumen Diameter (MLD) at 3 years post nitrate minus MLD post procedure post nitrate (non-inferiority, reflex to superiority)

• Up to 2 de novo lesions in different epicardial vessels Planned overlapping allowed in lesions ≤48 mm

• Scaffold diameters: 2.5, 3.0, 3.5 mm Scaffold lengths: 12, 18, 28 mm

Absorb Clinical Update ABSORB II – Absorb Patient/Lesion Demographics

• Moderately complex lesions – one or two de novo native lesions each located in a different epicardial vessel

• Lesion diameter of ≥2.25 mm and ≤3.8 mm

• Lesion length up to 48 mm

• Lesion classification (ACC/AHA) including A, B1, B2 and a few C

• 24% w/ diabetes

• 28% w/ prior MI

• 20% unstable angina

• 13% with moderate / severe calcium

Absorb Clinical Update ABSORB II – Clinical Outcomes

Absorb N=335

XIENCE N=166 p value

DoCE (Device-Oriented Composite Endpoint) 4.8 3.0 0.35

Cardiac death (%) 0 0 1.00

Target vessel MI (%) 4.2 1.2 0.07

Clinically indicated TLR (%) 1.2 1.8 0.69

All TLR (%) 1.2 1.8 0.69

Definite Scaffold/Stent Thrombosis (%) 0.6 0.0 1.00

PoCE (Patient-Oriented Composite Endpoint) 7.3 9.1 0.47

All death (%) 0 0.6 0.33

All MI (%) 4.5 1.2 0.06

All NQMI (%) 3.9 1.2 0.16

All QMI (%) 0.6 0 1.00

All revascularization (%) 3.6 7.3 0.08

DoCE - Composite of cardiac death, target vessel MI and clinically indicated target lesion revascularization PoCE - Composite of all death, all MI and all revascularization Adapted from Serruys, P.W. TCT 2014

Absorb Clinical Update ABSORB II – Reduction in Patients’ Angina Status

ABSORB II Angina at 1 Year

1 - Excludes in-hospital or the first 7 days, whichever is earlier Adapted from Serruys, P.W. TCT 2014

Patients experiencing angina demonstrated higher rates of nitrate utilization and impaired performance on Exercise Tolerance Testing (ETT)

16.4%

25.6%

0%

5%

10%

15%

20%

25%

30%

Absorb n=335 XIENCE n=166

Inci

denc

e (%

)

p=0.01 Δ=36%

Absorb Clinical Update ABSORB II – Summary

Absorb demonstrated similar safety and efficacy as compared to XIENCE at 1- year in this randomized study

Two definite scaffold thromboses were documented, one acutely within 24 hours after the procedure and the second case sub-acutely on day 2. The rate of definite scaffold thrombosis was 0.6% in the Absorb arm and 0% in the Xience arm (p=1.0).

Exercise performance and angina status as assessed by SAQ were comparable, however a difference in nitrate use was observed at 6 months (17.8% vs 26.7%, p=0.02) and 12 months (19.5% vs 26.2%, p=0.09) in favor of the Absorb arm.

The difference in cumulative rates (21.8% in the Absorb arm vs 30.5% in the Xience arm, p=0.04, 16.4% vs 25.6%, p=0.015 if the first 7 days are excluded) of angina according to AE reporting (recurrent or worsening angina) is a post-hoc, hypothesis generating observation that warrants further physiological and clinical investigation.

At one year, DoCE (cardiac death, TV-MI and TLR, Absorb: 4.8% vs Xience: 3.0%, p=0.35), PoCE (all death, all

MI and all revascularization, Absorb:7.3% vs Xience: 9.1%, p=0.47) and their components were similar between the two arms.

Lancet 2014, PWS…..

Absorb Clinical Update ABSORB Cohort B – Imaging at 5 Years

Baseline

6 Months

2 Years

5 Years

Cohort B OCT images - courtesy of RJ van Geuns, Erasmus Medical Center, Netherlands De Bruyne, B. TCT 2014

Absorb Clinical Update ABSORB EXTEND – Reduction in Long-Term Events

Clinical Outcomes at 3 Years – Propensity Score Matched Analysis*

Adapted from Smits, P. TCT 2014 *Absorb patients from ABSORB EXTEND; XIENCE V patients from SPIRIT I/II/III. **Stent/scaffold thrombosis (ARC Definite/Probable). MACE is the composite of cardiac death, MI (Q-wave and Non-Q wave MI) and ID-TLR. TVF is the composite of cardiac death, TV-MI (Q-wave and Non-Q wave MI) and ID-TVR.

0%

3%

6%

9%

12%

15%

MACE TVF TLF ST**

Inci

denc

e (%

)

Absorb (n=174)

XIENCE (n=290)

p=0.36

p=0.05

p=0.31

p=1.00

7.5 8.0

6.9

10.0

14.1

9.7

0.6 0.7

Absorb Clinical Update ABSORB EXTEND – Reduction in Long-Term Events

Angina Status Through 3 Years –

Propensity Score Matched Analysis of ABSORB EXTEND and SPIRIT IV Populations*

0 37 194 393 758 1123#

Absorb Extend**

155 140 131 125 117 115

1.9% 9.7% 15.5% 19.4% 24.5% 25.8%

SPIV NC** 155 134 124 111 99 88

4.5% 13.5% 20.0% 28.4% 36.1% 41.3%

Difference 2.6% 3.8% 4.5% 9.0% 11.6% 15.5%

Adapted from Smits, P. TCT 2014

* EXTEND excludes non-Japanese Asians, and SPIRIT IV non-complex subgroup ** Includes in-hospital angina events; angina reported via AE forms # Out of hospital to 3 years angina rates: 23.9% (Absorb) and 43.2% (XIENCE)

Rita-2 OMT

(1997)

Courage OMT

(2007)

Courage BMS

(2007)

Rita-2 PTCA

(1997)

SPIV DES

(2009)

ABSORB II DES

(2014)

OMT PTCA BMS DES

ABSORB II Absorb (2014)

Absorb

Absorb Clinical Update Improvement in PCI Outcomes Over Time

Improvement in PCI Outcomes Over Time

58%

42% 38%

34%

27% 26%

16% 15% 16% 14% 15%

7% 7% 4%

0%

10%

20%

30%

40%

50%

60%

70%

Angina at 1yr post-intervention

Repeat revascularization

Inci

denc

e (%

)

Angina = CCS I/II/III/IV Post PCI Angina Sources: Rita 2 – Lancet 1997;350: 461-68; Courage - NEJM 2007;365:1503-16; SPIRIT IV - TCT 2013 Stone, FAME I – NEJM 2009;360: 213-24. Repeat revascularization Sources: Rita 2 – Lancet 1997 ;350: 461-68 (est from KM curve); Courage OMT - Circ Cardiovasc Qual Outcomes. 2013 Jul;6(4):409-18; Courage BMS - http://www.cathlabdigest.com/articles/The-COURAGE-Trial-Looking-past-controversy-patient-care; SPIRIT IV - TCT 2013 Stone, ABSORB II, TCT 2014

Goals of Vascular Reparative Therapy:

– Restore vasomotor function in some patients, for regulation of coronary blood flow

– Restore vessel compliance and cyclic strain in response to pulsatile flow

– Enable adaptive shear stress, allowing the vessel to regain its ability to maintain quiescent homeostasis

– Permit accommodative, beneficial remodeling

Potential for improved long-term outcomes

• Coronary artery disease in patients with diabetes

• Diffuse atherosclerotic involvement of epicardial vessels

• Extensive multivessel disease (higher tertile of Syntax score)

• PCI for ST-segment myocardial infarction and NSTEMI, especially in the case of high thrombus burden in large vessels

• residual risk related to non-culprit lesions in patients with acute coronary syndromes

• sudden ischaemic cardiac death; • treatment of complex bifurcation stenoses; • intervention for chronic coronary occlusion with the use

of simpler, safer, and less expensive tools and techniques.

« Les derniers défis de l’angioplastie » BARBATO, WIJNS, EHJ march 2014

SCAFFOLD STENT

Plus de malappostion dans les SCA

BARBATO, WIJNS, EHJ 2014

A.Latib,… A.Colombo Minerva Cardiologia 2014

Consensual and appropriate indications • 1. Young patients (aged <50 years) • 2. Diabetic patients • 3. Lesions in segments that may undergo CABG, particularly the LAD • 4. Vessels with long lesions (>30 mm) and/or diffuse disease with a

high probability of requiring secondary revascularization

Less consensual but possible indications • 1. Small collateral branches (<1.5 mm) • 2. Non-ST elevation acute coronary syndrome, stabilized, with intermediate and/or

unstable plaques • 3. ST-elevation acute coronary syndrome, stabilized, with intermediate and/or

unstable plaques

Inappropriate indications • 1. Left main disease • 2. Moderate or severe tortuosity • 3. Severe calcification • CABG: coronary artery bypass grafting.

R.C. Teles , Rev Port Cardiol. 2013;32(12):1013---1018

Plutôt 65 à ROUEN !!!!!

Homme, 50 ans, Diabétique, 3 VX, angor d’effort

2 BVS IVA - 1 BVS Mg

FFR BASAL CD

CD APRES STENT SEG II

CD FINAL

Femme, 37ans, SCA, 3 VX, DNID I.R.

Registre France ABSORB

Promoteur : SFC / GACI

Sponsor : Abbott Vascular

Investigateurs principaux : Dr René Koning / Pr Hervé Le Breton

Comité Scientifique : Bureau du GACI (Groupe Athérome et Cardiologie Interventionnelle de la SFC)

Comité de surveillance des évènements : - Dr Pierre Meyer (Institut Arnaud Tzanck- Saint Laurent du Var) - Pr Christophe Bauters (CHU-Lille)

Registre France ABSORB (demandé par ANSM)

Registre observationnel, prospectif, multicentrique

L’ensemble des patients implantés d’un ABSORB BVS en 2014 et 2015

Au moins 2000 pts

Nb de centres : l’ensemble des centres implantant le BVS

Cahier d’observation : e-CRF

100 % des évènement seront revus et validés par un CEC

End point primaire: MACE à 12, 24, 36, 48 et 60 mois

Timelines France ABSORB Registry

Q1 2014 Q2 2014

France ABSORB

Registry

Soumission CCTIRS février 2014

Q3 2014

Soumission CNIL

- Finalisation du e-CRF -Confirmation des membres du CEC

Q4 2013

- Protocole - CIP - e-CRF - Signature du

contrat, Dec 13

Avis favorable CTTIRS 10 avril 14

AVIS positif CNIL

Tous les centres ouverts

Q4 2014

Liste des centres Conventions centres

/SFC

Mise en ligne du e- CRF

LE BIO RESORBABLE VA-T-IL DEVENIR LE GOLD STANDARD ?