Orsiro´s Concept - SOLACI

Ultrathin strut bioabsorbable polymer DES construction: Orsiro´s Concept

Simpósio Satélite -- BIOTRONIK

08 June2016-12h15-12h35

Costantino R. Costantini, M.D., Ph.D., F.A.C.C. Hospital Cardiológico Costantini Fundação Francisco Costantini

Curitiba - Brasil

Room Lagoa de Freitas

• Palestrante: Costantino R Costantini

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Costantino R. Costantini, M.D., Ph.D., F.A.C.C.

Hospital Cardiológico Costantini

Foundaction Francisco Costantini

Curitiba - Brazil

29/08 - 17:45 - 20:00hs

Orsiro: el primer DES híbrido del mercado y los resultados de los estudios

clínicos (BIOFLOW-II y III)

Buenos Aires Argentina 2013

REDUCE INFLAMMATORY RESPONSE, IMPROVE ENDOTHELIALIZATION, PROMOTE VASCULAR HEALING

Unique Hybrid Technology

sirolimus

• 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

The BIOlute® polymer matrix

gently degrades into CO2 and

H2O

Only a PROBIO® sealed stent

is left in the arterial wall

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)

The device: Orsiro Hybrid Drug Eluting Stent

Progress with metallic drug-eluting stents

Antiproliferative drug Sirolimus-analogues Paclitaxel

Polymer material

Stainless steel Cobalt-Chromium/Platinum-Chromium

Taxus Cypher BioMatrix Nobori

Endeavor Yukon PC Xience Promus

Resolute Synergy Orsiro DESyne Combo Mistent Ultimaster

132 140 120 91 87 81 91 74 60 81 100 64 80 (μm)

Platform material & strut thickness

SES BES ZES SES EES ZES EES SES NES SES SES SES

Sirolimus Biolimus Zotarolimus Everolimus Novolimus

Durable polymer Biodegradable polymer

Drug Release Kinetics and Polymer Coating Biodegradation

Sirolimus Drug Load: 1.4 μg/mm² PLLA metabolizes into CO2 and H2O

Source: Data on file, BIOTRONIK AG.

Pre-clinical Histology Data (Mean Values @ 28 Days)

Koppara T, Thromb Haemost. 2012

ORSIRO

BIOFLOW III

Methods: This prospective, multicentre, observational, all-comers registry enrolled

1,356 patients with diabetes mellitus, small vessels, chronic total occlusion and

acute myocardial infarction, respectively.

EuroIntervention 2016;11:1106-1110

BIOFLOW III


LOW TLF and ST RATES IN NA UNSELECTED, ALL- COMMES POPULATION WITH

COMPLEX CORONARY ARTERY DISEASE

Target Lesion Failure @ 12 months Definite Stent Thrombosis @ 12 months

BIOFLOW III Primary Efficacy and Safety Endpoints


Investigator City Patients

Thomas Pilgrim, MD Bern 1,216

Marco Roffi, MD Geneva 209

David Tüller, MD Zurich 179

André Vuilliomenet, MD Aarau 102

Olivier Muller, MD Lausanne 101

Stéphane Cook, MD Fribourg 100

Daniel Weilenmann, MD St. Gallen 99

Christoph Kaiser, MD Basel 60

Peiman Jamshidi, MD Lucerne 53

2,119 patients were enrolled across 9 centers in Switzerland

Genev

a

Lausann

e

Fribourg

Bern

Basel

Lucerne

Aarau

Zurich St.

Gallen

PATIENT RECRUITMENT February 2012 to May 2013

BIOSCIENCE

PATIENT FLOW 2,129 patients randomised

2,119 patients included

10 provided preliminary consent but refused definite consent

1,031 follow-up information for primary endpoint available

1,036 follow-up information for primary endpoint available

1,056 analysed for primary clinical endpoint

- 20 censored at timepoint of refusal or loss to follow-up

1,063 analysed for primary clinical endpoint

- 32 censored at timepoint of refusal or loss to follow-up

BIOSCIENCE

1,063 allocated to biodegradable polymer sirolimus-eluting stent

ORSIRO (1,594 lesions)

1,056 allocated to durable polymer everolimus-eluting stent

XIENCE (1,545 lesions)

LIMUS

BIOSCIENCE @ 24 months

PRIMARY EFFICACY COMPOSITE ENDPOINT Target Lesion Failure @ 24 months Definite Stent Thrombosis @ 12 months

SIMILAR LONG-TERM EFFICACY AND SAFETY COMPARED TO BEST-IN-CLASS NEWER-GENERATION

DP-DES IN ALL-COMERS POPULATION WITH COMPLEX PATIENT AND LESION CHARACTERISTICS

Zbinden R, Jam Heart Assoc. Mar 2016; 15;4(3)

XIENCE 10.4 %

ORSIRO 10.5 %

Zbinden R, Jam Heart Assoc. Mar 2016; 15;4(3)

BIOSCIENCE @ 24 months

COMPOSITE OF PRIMARY EFFICACY ENDPOINT

TLF C. DEATH

T VESSEL MI TLR Clinical drivent

Risk ratio (95% CI)

Favours BP SES Favours DP EES

Target lesion failure

Bioflow-II

Bioscience

Cardiac death

Bioflow-II

Bioscience

Target vessel myocardial infarction

Bioflow-II

Bioscience

Target lesion revascularisation

Bioflow-II

Bioscience

BP SES DP EES

0.82 (0.41-1.64)

0.98 (0.71-1.35)

0.95 (0.71-1.27)

19/298

69/1,063

12/154

70/1,056

1.03 (0.09-11.31)

0.90 (0.50-1.64)

0.91 (0.51-1.63)

2/298

20/1,063

1/154

22/1,056

1.03 (0.32-3.38)

0.96 (0.59-1.58)

0.97 (0.62-1.53)

8/298

30/1,063

4/154

31/1,056

0.74 (0.29-1.90)

1.51 (0.90-2.54)

1.18 (0.61-2.30)

10/298

35/1,063

7/154

23/1,056

0.25 0.5 1 2 4

Risk ratio (95% CI)

Meta-analysis of BIOSCIENCE, BIOFLOW II

Costantino R. Costantini, M.D., Ph.D., F.A.C.C.

Hospital Cardiológico Costantini

Foundaction Francisco Costantini

Curitiba - Brazil

29/08 - 17:45 - 20:00hs

Orsiro: el primer DES híbrido del mercado y los resultados de los estudios

clínicos (BIOFLOW-II y III)

Buenos Aires Argentina 2013

TCTMD,Wednesday, June 15, 2011

MARCO !!!!! NO INTERVENCIONISMO

?

Orsiro Stent Registry HCC Brazil ( 2013)

Clinical endpoint

assessment

Angiographic & IVUS

endpoint assessment

30 d 3 mo 6 mo 12 mo

• Design: Prospective, uni-centre registry

• Patient Number: 25

• Patents with angiographic follow-up: 21 patients

• Patients with IVUS follow-up: 21 with 35 stents

• Follow-up rate: 84 %

• Enrollment time: Between 26 nov 2011 at Aug 2013

HCC Orsiro Stent Registry

30 days clinical results N %

Death 0 0.0

Stent thrombosis 0 0.0

MI 0 0.0

TLR (clinically driven) 0 0.0

MACE 0 0.0

Clinical outcomes at 30 days

25 Patients 40 stents


6-month clinical results N %

Death 0 0.0


MI 0 0.0

TLR (clinically driven) 0 0.0

MACE 0 0.0

Clinical outcomes at 6 months

25 Patients 40 stents


25 pts-results N %

Death ( Not Cardiac) 1 3,95


MI 0 0.0

TLR 2 7,90

TVR 2 7,90

MACE 3 11,85

Clinical outcomes at 12 months

25 Patients with 40 stents

Clinical and angiographics results


Orsiro

Case presentations

Patient

01

LCx (stable Angina)

MCS ♀ - 65 Yrs 30041 – 26Nov11

Orsiro 4.0 * 26

Orsiro 4.0 * 9

Pré Pós

19.28 mm²

11.27 mm²

CardioInterv 2011

MCS ♀ - 65 Yrs

Orsiro 4.0 * 9

30041 – 26Nov11

F/U @ 12 mo

32321 – 21Nov12

Pre Post

15.57 mm²

15.68 mm²

LCx (stable Angina)

Case presentation

Pre, Post and F/U @ 12 months

CardioInterv 2011

Orsiro 4.0 * 26

Orsiro

Case presentations

Patient

02

RCA (stable Angina)

MND ♀ - 62 Yrs 30058 – 28Nov11

Orsiro 3.0 * 30

Orsiro 2.5 * 30

Pre Post

CardioInterv 2011

5.81 mm²

7.89 mm²

Proximal Distal

MND ♀ - 63 Yrs 32630 – 10Dec12

Follow Up @ 12 months

IVUS + OCT

5.26 mm² 5.19 mm² 7.03 mm²

1 2 3

1) 2) 3)

*

*

*


Orsiro Stent -- OCT -- F/U @ 12 mo

MND ♀ - 63 Yrs 32630 – 10Dec12

Orsiro

Case presentations

Patient

03

(Caso 03) RCA (Stable Angina)

HV ♀ - 78 Yrs

30070 – 29Nov11 32145 – 19Nov12

Orsiro 3.0 * 26

Orsiro 2.5 * 26 F/U @ 12 mo

6.37 mm²

15.65 mm² 13.41 mm²

6.15 mm²

CTO

Pre Post

CardioInterv 2011

Orsiro

Case presentations

Patient

09

MCZ ♂ - 56 yrs 30324 - 04Jan12

1.96 mm² 1.66 mm²

Case 09 presentation

Unstable Angina

LAD Proximal Lesion

LAD Mid Lesion

44 mm

Distal Ref. Proximal Ref.

MCZ ♂ - 56 yrs 30324 - 04Jan12

5.07 mm² 7.53 mm²


Final Result

Orsiro 2.75 * 22

Orsiro 2.75 * 22

Distal Ref. Proximal Ref. Boost

Proximal Stent Distal Stent

MCZ ♂ - 56 yrs 31584 – 10Jul12

5.02 mm² 6.98 mm²



Distal Ref. Proximal Ref.

Orsiro

Case presentations

Patient

10

MBG ♂ - 66 yrs 30374 - 12Jan12


Unstable Angina

3.64 mm²

LAD

3.84 mm²

DG

IVUS Plaque caracterization:

LAD: Deep calcific

Cutting Balloon !!!

Pre Procedure

MBG ♂ - 66 yrs 30374 - 12Jan12

3.64 mm²

LAD


LAD: Deep calcific

4.58 mm²

LAD

7.12 mm²

LAD Stent

LAD Calcific Plaque

IVUS Optimization

Plaque Preparation is essential

MBG ♂ - 66 yrs 30374 - 12Jan12

LAD Calcific Plaque

IVUS Optimization

4.58 mm²

LAD

Post Cutting

Balloon !!!

2.5 * 10 at 10 ATms

Post Cutting

Balloon !!!

MBG ♂ - 66 yrs 30374 - 12Jan12

Final Result

Angio + Boost + IVUS

Post BOOST 7.12 mm²

LAD Stent

Orsiro 3.0 * 32

MBG ♂ - 66 yrs

Image Pre, Post & F/U

Pre

Post

Orsiro 3.0 * 32

30374 – 12Jan12 32503 – 28Nov12

MLA: 6.25 mm²

F/U @ 12 months

Volumetric Echoplaque Indec System 2009

Orsiro

Case presentations

Patient

14

Case 14 presentation (3VD)

Inferior MI 4 hour on Set

LVEF: 75 %

PRE POST

PBJ ♂ - 52 yrs 31568 - 06Jul12

2.00 mm²

DPCD

VPCD

2.50 mm²

Post Kissing Balloon


Fibrotic, superficial calcific

Orsiro 3.0 * 15

Orsiro 3.5 * 26

PBJ ♂ - 52 yrs 31568 - 06Jul12

6.83 mm²

DPCD

8.79 mm²

VPCD

Distal RCA

10.94 mm²

DPCD

VPCD

RCA

Orsiro Stent in AMI

Final Result - With IVUS Evaluation


Second stage (LAD & LCx)

PBJ ♂ - 52 Anos 32548 – 29Nov12

Final Result

PBJ ♂ - 52 Yrs 32548 – 29Nov12

Orsiro 3.0 * 22

Orsiro 2.75 * 9

Orsiro 2.5 * 18

7.17 mm²

6.36 mm²

6.30 mm²


RCA F/U @ 13 mo

PBJ ♂ - 53 Yrs 34240 – 19Aug13

8.75 mm²

RCA-PVA RCA-PDA

6.79 mm²

6.21 mm²

6.12 mm²


LAD / LCx F/U @ 9 mo

PBJ ♂ - 53 Yrs 34240 – 19Aug13

5.64 mm²

Orsiro

Case presentations

Patient

15


Unstable angina -- Thallium test (+) apical wall

(CTO) LVEF: 75 %

TJA ♀ - 75 Yrs 31579 – 10jul12

7,66 mm²

5,90 mm²

Orsiro 3.0 * 26

Orsiro 2.5 * 22

Follow Up 12 mo

Angiograma + IVUS + OCT -- DA

1

1

2

2

3

3

3

0,25mm

0,21mm 0,21mm

6,81 mm²

1

2

6,79 mm²

TJA ♀ - 76 Yrs 34041 – 23jul13

Orsiro

Case presentations

Patient

16

LRK ♀ - 79 Yrs 31629 – 13jul12

Case 16 presentation (Long Lesion)

Unstable Angina

Pre, post balloon & IVUS

2.39 mm²

Proximal Distal

Balloon 2.0 * 10

LRK ♀ - 79 Yrs 31629 – 13jul12


Unstable Angina

Post Orsiro & IVUS

6.46 mm²

Proximal Distal

Orsiro 2.75 * 30

F/U @ 13 mo (IVUS & OCT)


LRK ♀ - 80 Yrs 31629 – 26Aug13

6.31 mm² 6.35 mm² 6.18 mm²

Orsiro

Case presentations

Patient

18

GVL ♂ - 64 yrs 31849 – 17Aug12

Case 18 presentation (CTO)

Collatheral

Ustable Angina

GVL ♂ - 64 yrs 31849 – 17Aug12


Unstable Angina

Final Result

Orsirio 3.5 * 30

8.21 mm²

Balão

GVL ♂ - 65 yrs 34271 – 22Aug13


F/U @ 12 mo

12.17 mm² 7.22 mm² 7.18 mm²

DG

Óstium

Orsiro

Case presentations

Patient

25

JCS ♂ - 55 yrs 32554 30Nov12

Ustable Angina

ISR Previous stent BMS in Acute MI

BMS Feb2011


CardioInterv 2012

2.23 mm² 5.60 mm² 7.98 mm²

Post Balloon Post Cutting Balloon Post New Stent (Orsiro)

JCS ♂ - 55 yrs 32554 30Nov12

Orsiro 3.0 * 26


CardioInterv 2012

Vol. Hyperp. Vol.

9,1± 3,1 mm³

Vol Stent

89,3 ± 32,1 mm³

Vol Vessel

142,2 ± 47,6 mm³

IVUS follow-up 12 mo

21 patients (35 Stents)

LATE LOSS BY IVUS 0,18 mm

BIOFLOW-I results in perspective

Overview of in stent late lumen loss in FIM trials

* 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.

FIM SR3

4 m

n=15

Nevo

Nevo Res-I2*

6 m

n=186

XienceV

SPIRIT First1

6 m

n=28

Endeavor Resolute Orsiro BIOFLOW-I

9 m

n=30

FIM FR3

4 m

n=15

FIM4

4 m

n=30

FIM5

9 m

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 0.07

Orsiro HCC

REAL WORLD

12 m

n=25

Baseline clinical characteristics

N=25

Age, years 62,48 yrs ± 11.70

Male sex 52 % 13/25

Hyperlipidemia 64 % 16/25

History of MI 20 % 5/25

Hypertension 80 % 20/25

Smoker 04 % 1/25

Diabetes 28 % 7/25

CHF 56 % 14/25

Previous CABG 08 % 2/25


Baseline lesion characteristics Pre-Procedure N= 33 lesions

Syntax mean: 26

Mean stent: 1,6 stent per patient

RVD (mm) 2.67 ± 0.28

MLD (mm) 0.97 ± 0.26

% Diameter stenosis 91.6 ± 8.4

Mean Lesion length (mm) 18.21 ± 5.22

Procedural N= 40 stents

Stent length per lesion (mm) 22,72 ± 6.39

Stent diameter per lesion (mm) 3.02 ± 0.44

Direct stenting 0%

Device success* 100.0%

IVUS Guided 100.0%

* Defined as In-Stent < 30% residual stenosis by offline QCA

29

1441

16

Lesion Type

A

B1

B2

C

5224

24

Lesion Location

LAD

RCA

LCx


ORSIRO HYBRID DRUG-ELLUTING STENT

RATES OF TARGET LESION FAILURE (%) @ 9-12 MONTHS

ORSIRO HCC

350 pts

IVUS IN

89%

Orsiro Stents

Case 4

Caso Complexo

Multi Arterial com lesão de TCESQ

BVS e ORSIRO

Orsiro Stents

Case 4

Caso Complexo

Multi Arterial com lesão de TCESQ

BVS e ORSIRO

Apresentação clínica

• P.A.C, 76 anos, masculino, assintomático

• 04Fev15 Angiotomo: Lesões severas CD e DA

• Encaminhado para cateterismo cardíaco

• Hipertensão

• Dislipidemia

• FEVE: 77%

• Syntax Score 13

PAC ♂ - 76 Anos 37906 – 24Mar15

Resultado Angiografia

3.47 mm² 2.33 mm²

1/3 Médio 1/3 Distal

Avaliação Anatômica vs Funcional

PAC ♂ - 76 Anos 37943 – 30Mar15

Extremo Distal

2.79 mm²

FFR

0,89

FFR CLASE I A ??

PAC ♂ - 76 Anos 37943 – 30Mar15

Absorb

3.5*18

Absorb

2.5*28

Balão

2.5*20

Implante Absorb Descendente Anterior Distal

Extremo Distal Distal

Orsiro

3.5*18

9.50 mm²

DA Stent TCESQ

PAC ♂ - 76 Anos 37943 – 30Mar15

Tronco de Coronária Esquerda

Descendente Anterior

Balão

6.0*12 Orsiro

4.0*9 Mal Aposição

21.23 mm²

TCESQ

Pós Reintervenção

Tronco de Coronária Esquerda

PAC ♂ - 76 Anos 37943 – 30Mar15

TCESQ

Pós Reintervenção

Balão

3.78 mm²

CD Placa Ulcerada

PAC ♂ - 76 Anos 37943 – 30Mar15

Coronária Direita pré e pós

15.95 mm²

CD Pós Stent Orsiro

4.0*22

Ca Ca

ORSIRO HYBRID DRUG-ELLUTING STENT

HOSPITAL COSTANTINI REGISTRY ALL PATIENTS -- 561 WITH 834 STENTS (NOV 2011 – MAY 2016)

FOLLOW UP 350 PATIENTS WITH 511 STENTS

OUTCOMES @ 36 MONTHS

37% MULTI VESSEL AND 23 % DIABETICS

IVUS IN

89%

We both, cardiologists and surgeons, Have and important mission:

To cure our patients ..... We are required to have: Professional excellence Good judgment Highest skills And especially.....

Frans van Mieris, 1657

Kunsthistorisches Museum, Viena

Pomar, R TEAM 2010

HONESTY

16 th International Interventional Cardiology Symposium

November 24, 25 - Curitiba - Brazil

Conferences, discussions, round tables and live cases.

20

16

LIVE CASES: TAVI- LEFT ATRIAL APPENDAGE –ESTRUTURAL-BRS-MULTIPLES VESSEL- NEW DEVICES

November 24,25 ----- Curitiba - Brazil

16 th International Interventional Cardiology Symposium

November 24, 25 - Curitiba - Brazil

Conferences, discussions, round tables and live cases.

20

16

LIVE CASES: TAVI- LEFT ATRIAL APPENDAGE –ESTRUTURAL-BRS-MULTIPLES VESSEL- NEW DEVICES

November 24,25 ----- Curitiba - Brazil

Orsiro´s Concept - SOLACI

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