RIBS VI: A Prospective, Multicenter, Registry of

Bioresorbable Vascular Scaffolds in Patients With Coronary Artery

Bare-Metal or Drug-Eluting In-Stent Restenosis

RIBS VI: A Prospective, Multicenter, Registry of

Bioresorbable Vascular Scaffolds in Patients With Coronary Artery

Bare-Metal or Drug-Eluting In-Stent Restenosis

Fernando Alfonso MD, PhD, FESCHospital Universitario “La Princesa” Madrid. Spain.

On Behalf of the RIBS VI Investigators

Javier Cuesta MD, Fernando Rivero MD, María J. Pérez-Vizcayno MD, Bruno García MD, José R. Rumoroso MD, Francisco Bosa MD, Armando Pérez de Prado MD, Mónica Masotti MD,

Raúl Moreno MD, Angel Cequier MD, Hipólito Gutiérrez MD, Arturo García-Touchard MD, José R López-Mínguez MD, Javier Zueco MD.

Fernando Alfonso MD, PhD, FESCHospital Universitario “La Princesa” Madrid. Spain.

On Behalf of the RIBS VI Investigators

Javier Cuesta MD, Fernando Rivero MD, María J. Pérez-Vizcayno MD, Bruno García MD, José R. Rumoroso MD, Francisco Bosa MD, Armando Pérez de Prado MD, Mónica Masotti MD,

Raúl Moreno MD, Angel Cequier MD, Hipólito Gutiérrez MD, Arturo García-Touchard MD, José R López-Mínguez MD, Javier Zueco MD.

Disclosure Statement of Financial Interest

I, [Fernando Alfonso, MD, and the coauthors], DO NOT have a financial interest/arrangement or affiliation with one or more organizations that could be perceived as a real or apparent conflict of interest in the context of the

subject of this presentation

RIBS VI

Management of patients with in-stent restenosis (ISR) still remains a challenge.

The role of bioresorbable vascular scaffolds (BVS) in these patients is unknown.

However, the potencial benefits of their strongantiproliferative effects without the need of an additionalpermanent metal layer, make these devices an attractivestrategy in this scenario.

Management of patients with in-stent restenosis (ISR) still remains a challenge.

The role of bioresorbable vascular scaffolds (BVS) in these patients is unknown.

However, the potencial benefits of their strongantiproliferative effects without the need of an additionalpermanent metal layer, make these devices an attractivestrategy in this scenario.

Background:

Objective:

To assess the efficacy of BVS in the treatment of patientswith ISR.

To compare BVS results with those obtained with drug-eluting balloons (DEB) and everolimus-eluting stents (EES) in the RIBS IV and RIBS V RCT

- Primary Endpoint: MLD at Follow-up

- Clinical Endpoint: Combined (Cardiac D, MI,TVR/TLR)

To assess the efficacy of BVS in the treatment of patientswith ISR.

To compare BVS results with those obtained with drug-eluting balloons (DEB) and everolimus-eluting stents (EES) in the RIBS IV and RIBS V RCT

- Primary Endpoint: MLD at Follow-up

- Clinical Endpoint: Combined (Cardiac D, MI,TVR/TLR)

RIBS VI

ClinicalTrials.gov ID: NCT02672878

1.- Asturias, HU Central Asturias.

2.- Badajoz, HU Infanta Cristina.

3.- Barcelona, HU Bellvitge.

4.- Barcelona, HU Clinic.

5.- Barcelona, HU Sant Pau.

6.- Barcelona, HU Vall D’Hebrón.

7.- Canarias, HU de Canarias

8.- Cantabria, HU Marques de Valdecilla.

9.- Santiago Compostela, HU Santiago

10.- León, HU CA de León

11.- Madrid, HU 12 de Octubre.

12.- Madrid, HU La Paz.

13.- Madrid, HU La Princesa

14.- Madrid, HU Puerta de Hierro.

15.- Madrid, HU Ramón y Cajal.

16.- Málaga, HU Virgen de la Victoria.

17.- Toledo, H U Virgen de la Salud Toledo

18.- Valladolid, HU Clínico de Valladolid

19.- Vizcaya HU Galdakao

1.- Asturias, HU Central Asturias.

2.- Badajoz, HU Infanta Cristina.

3.- Barcelona, HU Bellvitge.

4.- Barcelona, HU Clinic.

5.- Barcelona, HU Sant Pau.

6.- Barcelona, HU Vall D’Hebrón.

7.- Canarias, HU de Canarias

8.- Cantabria, HU Marques de Valdecilla.

9.- Santiago Compostela, HU Santiago

10.- León, HU CA de León

11.- Madrid, HU 12 de Octubre.

12.- Madrid, HU La Paz.

13.- Madrid, HU La Princesa

14.- Madrid, HU Puerta de Hierro.

15.- Madrid, HU Ramón y Cajal.

16.- Málaga, HU Virgen de la Victoria.

17.- Toledo, H U Virgen de la Salud Toledo

18.- Valladolid, HU Clínico de Valladolid

19.- Vizcaya HU Galdakao

19

2

16

1

6

543

89

14

1215

1113

17

7

10

18

Research Promotor: Spanish Society of Cardiology (SSC)

Auspices: Working Group on Interventional Cardiology of the SSC

Coordinator Center: H. Universitario La Princesa Madrid.

Research Promotor: Spanish Society of Cardiology (SSC)

Auspices: Working Group on Interventional Cardiology of the SSC

Coordinator Center: H. Universitario La Princesa Madrid.

Investigators´́́́ driven initiativeUnrestricted research grants: Abbott Vascular

(StJude y Terumo)

Multicenter, Prospective, Angiographic FU

RIBS VI

Coordinating Center: Hospital Universitario La Princesa. Madrid.

Steering Committee: F. Alfonso (Chairman and Principal Investigator), J. Zueco, A. Cequier, C. Morís.

Clinical Events Committee: R. Hernández, M. Sabaté.

Coronary Angiography Core Laboratory: (Hospital Universitario La Princesa, Madrid) J. Cuesta, M.J. Pérez-Vizcayno.

Data Coordination, Safety Monitoring and Statistical Committee: J. Cuesta, M.J. Pérez-Vizcayno, Cristina Fernández.

Intravascular Ultrasound and Optical Coherence Tomography Committee: F. Alfonso J. Cuesta.

Sites and Investigators: In order of enrollment:

1Hospital Universitario La Princesa, Madrid, (F. Alfonso, J. Cuesta, F. Rivero, T. Bastante, A. Benedicto, M. García-Guimaraes); 2Hospital Universitario Vall d’Hebron, Barcelona, (B. García del Blanco); 3Hospital Universitario de Canarias (F. Bosa); 4Hospital Galdakao, Vizcaya (J.R. Rumoroso); 5Complejo Asistencial Universitario de León, León, (A. Pérez del Prado); 6Hospital Universitario Clinic de Barcelona, Barcelona, (M. Masotti); 7Hospital Universitario Infanta Cristina, Badajoz, (J.R. López-Mínguez); 8Hospital Universitario de Valladolid, Valladolid (H. Gutierrez); 9Hospital Universitario de Bellvitge, Barcelona, (A. Cequier); 10Hospital Universitario Marqués de Valdecilla, Santander, (J. Zueco); 11Hospital Universitario Puerta de Hierro, Majadahonda, (A. García-Touchard); 12Hospital Universitario La Paz, Madrid, (R. Moreno); 13Hospital Universitario 12 de Octubre, Madrid, (T. Velazquez); 14Hospital Universitario Sant Pau, Barcelona, (V. Martí); 15Hospitalario Universitario Central de Asturias, Oviedo, (C. Morís); 16Hospital Ramón y Cajal, Madrid (R. Hernández); 17Hospital Universitario Virgen de la Salud Toledo, Toledo, (J. Moreu); 18Hospital Universitario Virgen de la Victoria, Málaga, (J.M. Hernández); 19Complejo Hospitalario Universitario de Santiago, Santiago de Compostela (R. Trillo)

Study Organization

RIBS VI

Inclusion / Exclusion Criteria

Informed consent

Age 20 - 85 y

ISR (> 50% stenosis)Angina or silent ischemiaISR amenable for BVS

Informed consent

Age 20 - 85 y

ISR (> 50% stenosis)Angina or silent ischemiaISR amenable for BVS

Inclusion:Inclusion: Exclusion:Exclusion:

Stent Related:Stent location undefined

ISR <1 Month

Thrombus

Vessel diameter < 2.25 mmISR outside the Stent

General:Life expectancy < 1 y

Female in childbearing age

Problems FU angiographyIntolerance DAT

LVEF < 25%

Stent Related:Stent location undefined

ISR <1 Month

Thrombus

Vessel diameter < 2.25 mmISR outside the Stent

General:Life expectancy < 1 y

Female in childbearing age

Problems FU angiographyIntolerance DAT

LVEF < 25%

RIBS VI

Flow Diagram

Same RIBS CentersIncl/Excl / CriteriaInformed Consent

RIBS VIProspective, Angio FU

(BMS-ISR and DES-ISR)

141 9Mo (100%); 124 (88%) 1Y (17 Pending)

QCA

(95% of Eligible)

Primary End-point

134 PtsAngio FU

498 Pts ISR

309 Pts RIBS IV; 189 Pts RIBS V

Randomization

249 Pts

EES249 Pts

DEB

219 PtsAngio FU

223 PtsAngio FU

Mean: 257 days Mean: 270 days

100% Angio Success

SeQuent Please (B. Braun)

Xience Prime(Abbott Vascular)

498 1Y Clinical FU (100%)

442 Pts: 91% of Eligible

QCAPrimary End-point

January 2010August 2013

January 2010August 2013

141 Pts

BVSAbsorb

(Abbott Vascular)

100% Angio Success

April 2014December 2015

April 2014December 2015

ClinicalTrials.gov Identifier: NCT01239953 & NCT01239940

RIBS VI

BVS (141) DEB (249) EES (249)

Age (years) 65+10 67+10 65+10

Female 16 (11) 40 (16) 37 (15)

- Diabetes 72 (51)* 105 (42) 85 (34)

- Hyperlipidemia 113 (80) 179 (72) 183 (74)

- Hypertension 106 (75) 178 (72) 189 (76)

Unstable Angina 69 (49) 118 (47) 121 (49)

Stable Angina / Isch 72 (51) 131 (53) 128 (51)

Time to ISR (median days) 1770* 496 535

Clinical Characteristics

RIBS VI

BVS (141) DEB (249) EES (249)

- LAD 66 (47) 112 (45) 108 (43)

- RCA 44 (31) 80 (32) 77 (31)

- LCX 27 (19) 48 (19) 56 (23)

DES-ISR 70 (51) 154 (62) 155 (62)

Length ST (mm) 20±7 20±7 20±7

>1 Treatment of ISR 21 (15) 23 (9) 20 (8)

LVEF (%) 56±13 58±12 59±11

Angiographic Data

RIBS VI

BVS (141) DEB (249) EES (249)

Device Length 19+8 20+6 21+9

Max Pressure (atm) 20+4 18+4 20+4

Inflation Time (sec) 60+50 108+48 62+46

B/A Ratio 1.20+0.2 1.23+0.2 1.19+0.2

Cross-over 0 (0) 13 (5) 1 (0.4)

Success 141 (100) 249 (100) 249 (100)

Procedural Data

RIBS VI

QCA: In-Segment Analysis

Reference Diameter

0

0.5

1

1.5

2

2.5

3

p = 0. 29p = 0. 29

Lesion Length

0

2

4

6

8

10

12

14

16

p = 0.89p = 0.89

(mm)(mm)

CAAS II SystemCAAS II System

RIBS VI

2.7±0.52.7±0.5 2.6±0.52.6±0.5 2.7±0.52.7±0.512±612±6 12±712±7 12±612±6

DEBDEBBVSBVS EESEES

QCA: MLD at FU

0

0.5

1

1.5

2

2.5

MLD-FUMLD-FUp < 0.001p < 0.001(mm)(mm)

In-Segment(Primary Endpoint)

In-Segment(Primary Endpoint)

LesionLesion

SegSeg

RIBS VI

DEBDEBBVSBVS EESEES

0

0.5

1

1.5

2

2.5p < 0.001p < 0.001

In-LesionIn-Lesion

1.87±0.5 1.88±0.6 2.16±0.7

1.94±0.5 1.94±0.6 2.30±0.7

0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

Late LossLate Loss p < 0.05p < 0.05

(mm)(mm)

QCA: In-SegmentQCA: In-Segment

RIBS VI

DEBDEBBVSBVS EESEES

0.23 0.24

0.12

0

0.5

1

1.5

2

Acute GainAcute Gain p < 0.001p < 0.001

(mm)(mm)

1.161.24

1.47

RIBS VI

0

20

40

60

80

100

0 1 2 3 4

MLD (mm)

PRE POST

p <0.001p = 0.03

FU

p <0.001

__BVS

__DEB

__EES

(%)

RIBS VI

0

20

40

60

80

100

-20 -10 0 10 20 30 40 50 60 70 80 90 100

(%) Stenosis

(%)

POST

p < 0.001

p < 0.001

FU

PREp = 0.008

RE35 (16%)19 (9%)15 (11%)p = 0.07

__BVS

__DEB

__EES

RIBS VI

On multivariate analysis, after adjusting for all potentialconfounders:

- MLD at FU was significantly smaller

- % DS at FU was significantly larger

after BVS compared with EES treatment

On multivariate analysis, after adjusting for all potentialconfounders:

- MLD at FU was significantly smaller

- % DS at FU was significantly larger

after BVS compared with EES treatment

RIBS VI

Events at Final FU (1 Year)141 Pts (100%) 10 Mo FU; 1Y FU 124 Pts (88%) (17 Pts pending 1Y)

0

5

10

15

20

DeathDeath Def/Pr STDef/Pr ST AMIAMI TLRTLR TVRTVR

0 (0)0 (0) 1 (0.7)1 (0.7)

4 (2.8)4 (2.8)

16 (11.3)16 (11.3)

19 (13.5) 19 (13.5)

(%)

55

1010

1515

2020

AMI: 1 periprocedural; 1 definitive BVS thrombosis1 late SB closure; 1 definitive ST of a stent in another vessel segment

RIBS VI

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

0

20

40

60

80

100

%

Time (months)

Freedom from Cardiac Death, MI, TVR

Breslow, p = 0.12Log Rank, p = 0.14

91%

85%86%

__BVS

__DEB

__EES

RIBS VI

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

0

20

40

60

80

100

%

Breslow, p = 0.02Log Rank, p = 0.03

94%

87%87%

__BVS

__DEB

__EES

Time (months)

Freedom from Cardiac Death, MI, TLR

RIBS VI

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

0

20

40

60

80

100

%

Breslow, p = 0.002Log Rank, p = 0.002

97%

89%

__BVS

__DEB

__EES

89%

Time (months)

Freedom from TLR

RIBS VI

BVS are safe and effective in the treatment of selected

patients with ISR

BVS provide favorable late angiographic (restenosis rate

11%) and clinical results (TLR 11%) in these patients

The acute and late angiographic findings of BVS appear to

be similar to those obtained with DEB (“leave nothing behindstrategy”) but poorer than those seen after EES implantation

(caution required as historical controls from RCT were used)

Further studies with long-term follow-up will be required to

elucidate the relative value of BVS vs other well-established

therapeutic strategies in this challenging setting

BVS are safe and effective in the treatment of selected

patients with ISR

BVS provide favorable late angiographic (restenosis rate

11%) and clinical results (TLR 11%) in these patients

The acute and late angiographic findings of BVS appear to

be similar to those obtained with DEB (“leave nothing behindstrategy”) but poorer than those seen after EES implantation

(caution required as historical controls from RCT were used)

Further studies with long-term follow-up will be required to

elucidate the relative value of BVS vs other well-established

therapeutic strategies in this challenging setting

Conclusions: