Scaffold bioabsorbibles. Estado Actual y Proyección

Scaffold bioabsorbibles. Estado

Actual y Proyección

Roberto Botelho, MD, PhD

Montevideo, December 2014

Disclosure

• Investigator of:

ABSORB EXTEND

• DESolve

MeRes (Meril Life Sciences)

Stanza (480 Biomedical) Xinsorb (Huaan Biotechnology) Amaranth (Amaranth Medical) ART18Z (ART 2nd _generation) ART (Arterial Remodeling Technology) IDEAL (BTI 2nd _generation) BTI (Xenogenics Corp.) DESolve (Elixir Medical) Absorb BVS (BVS 1.1) BVS 1.0 (Abbott Vascular) REVA (REVA Medical) ReZolve (REVA 2nd generation) AMS 4.0 (Dreams 2nd generation) AMS 3.0 (Dreams 1st generation) AMS 1.0 (Biotronik) Igaki-Tamai (Kyoto Medical) BRS (Micropost)

FAME:

Primary Endpoint

Tonino PAL et al. NEJM 2009;360:213–24

FFR-guided

(n=509)

30 days

2.9%

90 days

3.8%

180 days

4.9%

360 days

5.3%

Angio-guided

(n=496)

Absolute difference in MACE-free survival

Days

Fr

eedom fr

om dea

th,

MI, r

ev

asc

0 60 120 180 240 300 360 0.70 0.75 0.80 0.85 0.90 0.95 1.00

MACE 13.3% vs. 18.2%

P=0.02

1005 pts with MVD undergoing PCI with DES were randomized to

FFR-guided vs. angio-guided intervention

Number at risk

XIENCE V 669 646 616 601 582 571 565 548 537 529 521 TAXUS 332 310 288 274 269 262 255 248 243 231 223

Months

SPIRIT III: Target Lesion Failure @5 years

TLF

(%)

1-year HR

0.56 [0.34, 0.90]

p=0.01

5-year HR

0.64 [0.46, 0.89]

p=0.008

9.2%

5.4%

Δ3.8%

19.0%

12.7%

Δ6.3%

TLF = cardiac death, target vessel MI, or ischemic-driven TLR

0%

5%

10%

15%

20%

25%

30%

0 6 12 18 24 30 36 42 48 54 60

TAXUS Express (n=332)

XIENCE V (n=669)

Stone GW et al. JACC 2011 (abstract)

Potential Advantages of BVS

• the restoration of the vasomotor tone

• Adaptive shear stress

• Late luminal enlargement and beneficial late

expansive remodeling

Vasomotion

Vessel area

(mm2₎

15.72

15.34

14.09

13.76

Mean lumen area

(mm2₎

6.95

6.17

6.56

8.09

Plaque area

(mm2₎

8.78

9.17

7.54

7.07

Interventional Plaque Regression by BVS: Substantial

lumen enlargement due to plaque regression with

adaptive remodeling (cohort A pt)

Pre-PCI

Post-PCI

6 months

2 years

5 years

6-mo Taxus

%NC 8%

%DC 2%

9-mo Taxus

%NC 28%

%DC 8%

22-mo Taxus

%NC 39%

%DC 20%

48-mo BMS

%NC 40%

%DC 25%

57-mo BMS

%NC 57%

%DC 15%

Transformation of Neointimal Hyperplasia to

Necrotic Core in BMS and DES

A

B

C

C

B

A

D

D

E

E

Arrow indicates a metallic marker

* Mesmo paciente – esse paciente também apresentou um TLR, não qualificado como ID-TLR (DS = 42%)

** Um paciente retirou o consentimento e perdeu as visitas de 9, 12, 18 meses e 2, 3, 4 anos; dois pacientes morreram de causas não cardíacas , um em 706 dias e outro em 888 dias pós procedimento *** MACE (Major Advanced Coronary Events) - Composto por morte cardíaca, infarto do miocádio (IM), revascularização de lesão alvo (TLR) por PCI or CABG (Coronary artery bypass grafting)

RESTAURAÇÃO REABSORÇÃO Hierarquia 6 Meses 30 Pacientes 1 ano 29 Pacientes** 2 anos 29 Pacientes** 5 anos 29 Pacientes** Fatores isquêmicos MACE*** 1 (3.3%)* 1 (3.4%)* 1 (3.4%)* 1 (3.4%)* Morte cardíaca 0 (0.0%) 0 (0.0%) 0 (0.0%) 0 (0.0%) IM 1 (3.3%)* 1 (3.4%)* 1 (3.4%)* 1 (3.4%)* IM com onda Q 0 (0.0%) 0 (0.0%) 0 (0.0%) 0 (0.0%) IM sem onda Q 1 (3.3%)* 1 (3.4%)* 1 (3.4%)* 1 (3.4%)* Fator isquêmico TLR 0 (0.0%) 0 (0.0%) 0 (0.0%) 0 (0.0%) por PCI 0 (0.0%) 0 (0.0%) 0 (0.0%) 0 (0.%) por CABG 0 (0.0%) 0 (0.0%) 0 (0.0%) 0 (0.%) Trombose do stent Def/Prob 0 (0.0%) 0 (0.0%) 0 (0.0%) 0 (0.0%) Serruys, TCT, 2011

ABSORB Coorte A (Intent-To-Treat Population, ITT)

Excelentes dados de longo prazo até 5 anos

1

1

R.J. van Geuns, PCR 2012. Images courtesy of Thoraxcenter, Erasmus MC, Rotterdam, The Netherlands Acompanhamento

6 meses

Acompanhamento

5 anos

OCT

MLA 6.35 mm2 MLA 8.77 mm2

IVUS

Reabsorção do Scaffold por imagens de IVUS e OCT

ABSORB Coorte A

ABSORB Coorte B (ITT)

longo prazo até

3 anos

MACE: morte cardíaca, IM, fator isquêmico TLR

TVF : morte cardíaca, IM, fator isquêmico TLR, fator isquêmico TVR TLF: morte cardíaca, IM , fator isquêmico TLR

*Um paciente perdeu o acompanhamento

Dudek, D., ACC 2012. Morte Cardíaca (%) Infarto do Miocárdio n (%) IM com onda Q IM sem onda Q Fator isquêmico TLR n (%) PCI CABG MACE n (%) 30 Dias 6 Meses n = 101 n = 101 0 0 0 0 2 (2.0) 3 (3.0) 2 (2.0) 3 (3.0) 2 (2.0) 0 2 (2.0) 0 0 0 2 (2.0) 5 (5.0) 1 ano n = 101 0 3 (3.0) 3 (3.0) 0 7 (6.9) 0 4 (4.0) 4 (4.0) 2 anos n = 100* 0 3 (3.0) 3 (3.0) 0 9 (9.0) TVF n (%) 2 (2.0) 5 (5.0) 7 (6.9) 11 (11.0) 0 6 (6.0) 6 (6.0) TLF n (%) _{2 (2.0)} 5 (5.0) 7 (6.9) 9 (9.0) 3 anos n = 100* 3 (3.0) 3 (3.0) 0 10 (10.0) 0 7 (7.0) 7 (7.0) 10 (10.0) 13 (13.0) Trombose de stent Def/Prob n (%) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0

Compreensão da evolução da perda luminal tardia ao longo do tempo

Absorb em 3 anos

vs.

XIENCE V em 2 anos

0 10 20 30 40 50 60 70 80 90 100 -0,6 0 0,6 1,2 1,8 2,4 36M ABSORB (Coorte B): 0.29 ± 0.43 mm (N=51)

Eventos não hierárquicos 1 ano (n=450) 2 anos (n=95) Morte cardíaca % (n) 0.2 (1)1 0.0 (0) Infarto do miocárdio % (n)2 2.9 (13) 5.3 (5) IM com onda Q 0.9 (4) 2.1 (2) IM sem onda Q 2.0 (9) 3.2 (3) Ischemia driven TLR % (n) 1.8 (8) 4.3 (4) CABG 0.2 (1) 0.0 (0) PCI 1.6 (7) 4.3 (4) MACE hierárquico % (n) 4.2 (19) 7.4 (7) TLF hierárquico % (n) 4.2 (19) 7.4 (7) Scaffold Thrombosis, Def/Prob % (n) 0.9 (4) 1.1 (1) 2

1 _{Paciente teve somente XIENCE V implantado na lesão alvo} 2 _{IM por definição de protocolo}

ABSORB EXTEND (ITT)

Resultados clinícos em 1 e 2

ano

s

Patients enrolled

From 11/11/2012 to 29/1/2014 N=1,189; 1,440 lesions (mITT*) OCT: 163/1184 (14.4%) IVUS: 171/1184 (13.8%)

30-day FU

**

N= 1,118/1,1189 eligible

(94%

)

6-month FU

**

N=904/1,189 eligible

(76%)

Age, years±SD 62±11 (1,189) Male 944/1,189 (79%) Diabetes mellitus 295/1,189 (25%) On insulin 106/1,189 (9%) Hyperlipidemia 629/1,189 (53%) Hypertension 874/ 1,189(74%) Smoker 351/1,189 (30%) Previous PCI 399/1,189 (34%) Prior CABG 55/1,189 (5%) Stroke/TIA 45/1,189 (4%) ACS 563/1,189 (47%) Unstable angina 157/1,189 (13%) NSTEMI 214/1,189 (18%) STEMI 192/1,189 (16%)

*Modified Intention to Treat = patients with ABSORB BVS implanted ** As of April 7, 2014

Cardiovascular Death

Ca rdi o vascul ar dea th (%)

1.0%

0 30 60 90 100 150 180 0 2 4 6 8 Time (days) Day 0 30 60 90 100 150 180 At Risk 1,189 1,103 1,025 1,025 1,025 1,025 799

Target Lesion Revascularization

TLR (%)

2.5%

0 30 60 90 100 150 180 0 2 4 6 8 Time (days) Day 0 30 60 90 100 150 180 At Risk 1,189 1,104 1,104 982 913 862 747

Scaffold Thrombosis

1.5%

• There were 20 cases of angiographically confirmed ST and three of probable ST.

• 70% occurred in the first month after PCI, at a median of 5 days, suggesting the need for scrupulous lesion selection and PCI

techniques when using BVS

• Intravascular imaging was performed in only 9 of 23 patients who experienced ST • 20 of 23 patients were on DAPT at the time of ST

ABSORB FIRST

1

st

1200 Patients distributed by Country

21

EMEA: 64 APAC: 21 LA: 2

• First patient enrolled: Jan. 21, 2013 by Dr. Rosli Mohd Ali at Insitut Jantung Negara Hospital in Kuala

Lumpur, Malaysia. Total 1200 patients enrolled by the end of April, 2014

•Enrollment completion: August 26, 2014 with a total of 1800 patients enrolled

21 Turkey (3; 0) Colombia (2; 27) Netherlands (3; 82) Belgium (5; 70) Spain (13; 191) France (3;31) Italy (1; 9) Saudi Arabia (3; 21) UAE (1; 54) Malaysia (5; 70)

Bahrain (1; 28) New Zealand (2; 31)

Singapore (3; 67) Philippines(1;2) Vietnam (1;4) Hong Kong (1; 0) Germany (12;341) Poland (1;12) Switzerland (5; 42) Thailand (2; 11) Jordan (1; 28) Austria (2; 41) Indonesia (3; 38)

(#sites, #patients)

Target Lesion Characteristics

22 22

Characteristics

L = 1454

Calcification

(Moderate/Severe)

17.0%

Bifurcation

12.2%

Tortuosity

10.7%

Total Occlusion

10.9%

Ostial lesion

6.0%

L: Lesions

Evidence of Ischemia at Index (N = 1200)

23 23

Angina (44.1%)

MI (Total 39.3%)

* Acute MI: < 72hrs; recent MI: >72hrs;

6,2% 27,6% 16,5% 26,6% 9,7% 3,0% 9,4%

0%

5%

10%

15%

20%

25%

30%

Silen t Isc hem ia Stab le An gina Unst able Angi na Acut e MI* Rece nt M I* Unk now Time _Others

ACS (55.8%)

Definite/Probable ST Rates up to 30 Days

24 24

Scaffold Thrombosis

ABSORB FIRST

(N=1200)

Early (0-30 days)

Acute (< 1 day)

Sub-acute (1-30 days)

0.42%

0.00%

0.42%

ABSORB II : A Prospective, Randomized

Trial of an Everolimus-Eluting

Bioresorbable Scaffold Versus an

Everolimus-Eluting Metallic Stent in

Patients with Coronary Artery Disease

TCT 2014 13 Sep 2014 - 17 Sep 2014 , Washington, DC - U.S.A

Plenary Session XII : Late-Breaking clinical Trials #2

Patrick W. Serruys

Imperial College, London, UK

Erasmus University MC, Rotterdam, the Netherlands

ICPS, Bernard Chevalier

Massy, France

on behalf of the ABSORB II Investigators

ABSORB II 1-Year Patient Flowchart

Intent To Treat

N=501

Absorb

BVS

N=335

N=334

N=331

N=329

(98.2%)

Xience

N=166

N=166

N=165

N=164

(98.8%)

1 subject consent withdrawn 3 subjects consent withdrawn 2 subjects consent withdrawn 1 subject died

Baseline

30-day

180-day

1-year

1 subject consent withdrawn

Cumulative incidence in percentage

_{335 pts} Absorb _{166 pts} Xience _value

p

Composite of cardiac death, target vessel MI and clinically indicated target lesion

revascularization (TLF)

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

Clinical Outcomes

Cumulative incidence in percentage

_{335 pts} Absorb _{166 pts} Xience _value

p

Composite of cardiac death, target vessel MI and clinically indicated target lesion

revascularization (TLF, DoCE)

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

Composite of all death, all MI and all

revascularization

7.3 %

9.1 %

0.47

All death

0 %

0.6 %

0.33

All MI

4.5 %

1.2 %

0.06

All revascularization

3.6 %

7.3 %

0.08

Clinical Outcomes

Cumulative incidence in percentage

_{335 pts}

Absorb

_{166 pts}

Xience

_value

p

Definite scaffold/stent thrombosis

Acute (0-1 day)

0.3 (1pt)

0.0

NS

Sub-acute (2–30 days)

0.3 (1pt)

0.0

NS

Late (31–365 days)

0.0

0.0

NS

Probable scaffold/stent thrombosis

Acute (0-1 day)

0.0

0.0

NS

Sub-acute (2–30 days)

0.0

0.0

NS

Late (31–365 days)

0.3 (1pt)

0.0

NS

0,3% 3,0% 5,7% 8,4% 11,1% 13,8% 16,5% 19,2% 21,9% 24,6% 0 30 60 90 120 150 180 210 240 270 300 330 360 390 0,6% 5,4% 10,2% 15,1% 19,9% 24,7%

Days Since Index Procedure

Cardiac Diagnostic Imaging Other Diagnostics (ETT, ECG, Enzymes) Cardiovascular Meds PCI

16.4%

25.6%

BVS Angina Episode XIENCE Angina Episode

Cu m ul ati v e A ng ina Ra te

16.4%

vs.

25.6%

,

p=0.015

Time to the First Occurrence of Angina(Worsening or Recurrent) and its Duration according to AE Reporting– Cumulative Rate Excluding first 7 days

Conclusion

• The 12-month performance of the second-generation

ABSORB bioresorbable everolimus-eluting scaffold

is similar to Metallic DES in RCT

• Registries raised small flags on thrombosis

• Majority during first 30 days

• Caution with adequate technique must be paid

• Time to event analysis should be at an adequate time

• 100u struts DESolve available