Javier Escaned MD PhD

Hospital Clinico San Carlos

Madrid, Spain

Syntax II: Innovación científica en investigación biomédica con elstent farmacoactivo Synergy.

Per

cuta

neo

us

Co

ron

ary

Inte

rven

tio

ns

(PC

Is)

Source: Medical Device Industry Estimates

PCI procedures in the DES era

US PCI Procedures in the DES era

DES failure

SYNTAX

DES overuse

FREEDOM

Myocardial revascularization modality and extent of CAD:

2014 ESC Clinical Practice Guidelines recommendations

ESC guidelines on stable CAD / European Heart Journal (2013) 34, 2949–3003

How to improve the results of Syntax

• Better stratification

• Assessment of risk for both CABG and PCI

• Ischaemia driven revascularization

• Improved success rate in CTOs

• IVUS guidance

• Ancillary tools

• … and better drug eluting stents!

Ischemia driven TLRRR (95%CI)

Colmenarez H, Escaned J Eurointervention 2013

Taxus (Syntax) stent versus new generation DES

Myocardial infarctionRR (95%CI)

Stent thrombosisRR (95%CI)

Taxus as a G1 comparator

Better G2 Better TaxusBetter G2 Better Taxus

Better G2 Better Taxus

SYNTAX II Study: putting PCI strengths together

Ischaemia drivenrevascularization

(iFR/FFR)

Higher successrates in CTO PCI

Better riskstratification(SYNTAX II

score)

Heart Teamdiscussion

New generationDES(Synergy)

IVUS-guided DES implantation

SYNTAX II: Clinicaltrials.gov identifier NCT02015832

Principal Investigators: J Escaned, A BanningChairman: PW SerruysDeputy chairman: V Farooq

SYNTAX II Study: putting PCI strengths together

Ischaemia drivenrevascularization

(iFR/FFR)

Higher successrates in CTO PCI

Better riskstratification(SYNTAX II

score)

Heart Teamdiscussion

New generationDES(Synergy)

IVUS-guided DES implantation

SYNTAX II: Clinicaltrials.gov identifier NCT02015832

Principal Investigators: J Escaned, A BanningChairman: PW SerruysDeputy chairman: V Farooq

Restenosis in the 90´s: a time-related,

response-to-injury phenomenon

Forrester JS et al. JACC 1991;17:758-69

Platelet depositionThrombosis

Leukocyte recruitment

SMC proliferation

Stent struts

Macrophages

Lipid ladenneointima

Strut

Strut

A:OCT image obtained at Hospital Clinico San Carlos / Madrid

B and C: In-stent neotherosclerosis (B) and inflammation after DES. From Renu Virmani / TCT 2012

A B

C

Strut

Delayed healing and neoatherosclerosis

after DES: a cause of stent failure

Fresh thrombus with an intense inflammatory infiltrate of WBCs and numerous eosinophils.

Late-acquired stent malapposition in IVUS / OCT

Peri-stent contrast staining

Cook S et al. Circulation 2009; 120: 391-399

Hypersensitivity reactions and arteritis

after DES: role of polymer and drugs

Xience V™ Resolute Integrity™

SYNERGY™ BVSBioMatrixFlex™

PROMUS Element™

Durable Polymer Coated Stents

Bioabsorbable Polymer Coated Stents

Bioabsorbablescaffold

CoCr81 µm

PtCr81 µm

CoCr89 µm

PtCr74 µm

SS120 µm

PLLA (polymer) 150 µm

Polymer and strut thickness in G2 DES

Eluting Polymer Distribution and Thickness

Conformal

8µm / side

Conformal

8µm / side

Conformal

6µm / side

Abluminal

4µm

Abluminal

10µm

Conformal

3µm / side

Polymer Load (16 mm stent)

500µg 520µg 297µg 113µg 260µg 7,404µg

Importance of synchronous polymer degradation

Data on file at Boston Scientific

PLGA Mass

Remaining Everolimus

% r

emai

nin

g

Time (days)300 60 90 120

100

80

60

40

20

0

Polymer bulk erosion Polymer surface erosion

Data on file at Boston Scientific

PLGA Mass

Remaining Everolimus

% r

emai

nin

g

Time (days)300 60 90 120

100

80

60

40

20

0

Polymer bulk erosion Polymer surface erosion

Importance of synchronous polymer degradation

+

+++

+

++

+++

+

+

+

+

From data presented by Mike Eppihimer @ EuroPCR 2013 VE-cadherin used as a marker of fucntional endothelial coverage

Improved EC function

Greater localization of VE-cadherin at cell junctions

Abluminal vs conformal polymerImproved EC barrier formation in abluminal coating

SYNERGY™PROMUS Element™

EVOLVE II: Stent thrombosis 12-monthsDefinite/Probable : ITT Population

No Definite/Probable stent thrombosis in the SYNERGY arm after day 6

SYNERGY

PROMUSElement Plus

Subacute (2-30 days) Late (30 days – 1 year)

0.6%(N=5)

0.4%(N=3)

P=0.50

Acute (≤1 day)

N=1(Probable)

N=5(2 Definite/3 Probable)

N=2(Definite)

0.9

4.7

1.7

0.5

4.3

2.6

0

4

8

12

Cardiac Death Target Vessel-RelatedMI

Clinically-indicatedTLR

Eve

nt

Rat

e (

%)

PROMUS Element Plus SYNERGY

Components of TLF

P=0.34 P=0.71 P=0.21

*Per protocol spontaneous MI is defined as rise and/or fall of cardiac biomarkers with ≥1 value >99th percentile of the URL + evidence of myocardial ischemia. Peri-PCI MI is defined as ≥1 of the following: i) biomarker elevations within 48 hours of PCI (based on CK-MB >3X URL), ii) new pathological Q waves, or iii) autopsy evidence of acute MI

Advantages of Synergy in patients with MVD

• Strut thickness

• Cell design

• Eluting polymer

• Radial strength

• Antiproliferative drug

• Navigability

• Expansion range

74 µm PtCr alloy

Open cell design

Biodegradable PLGA

Stent design + PtCr

Everolimus

Connectors + hypotube

High (max 5.7 mm)

SYNTAX II case presentation #2

Syntax: 43 pointsSyntax II 4-year mortality: PCI 8%, CABG 18%

Male 79 y.o. Diabetes, dyslipidaemia, peripheral vascular disease, severe COPD

n=450

Single arm international study using SYNTAX data as comparator

Primary endpoint:

Composite of MACCE rate at 1 year follow-up (using SYNTAX I definitions) compared to PCI arm of the SYNTAX I Trial

SYNTAX II: a study on the state-of-the-art PCI

SYNTAX II: a study on the state-of-the-art PCI

Secondary endpoints

• Rates of individual components of MACCE at 1 year• Composite of MACCE rate and its individual

components at 2-5 years follow-up (patient reported) • Myocardial Infarction – according to Universal MI

definition 2012 at all timepoints• Stent Thrombosis (ARC) definitions at all timepoints

Exploratory endpoint:

• Composite of MACCE at 5 years follow-up compared to CABG arm of the SYNTAX I Trial

SYNTAX II case

Syntax: 29 pointsSyntax II 4-year mortality: PCI 12%, CABG 11%

Male 80 y.o. Diabetes, dyslipidaemia, hypertension

Only one stenosis (1/4) required treatment on iFR/FFR assessmentOnly one stenosis required adenosine administration.

iFR 0.90 FFR 0.83

iFR 0.94

iFR 0.95

iFR 0.35

Result of physiologicalstenosis assessment

SYNTAX II case

74

37

16

47

1016

0%

10%

20%

30%

40%

50%

60%

70%

80%

Anatomical Syntax I Functional Syntax I

Anatomical

SYNTAX

score

Functional

SYNTAX

score

Low Moderate High Low Moderate High

SYNTAX risk categories

(n=19)

Reclassification of multivessel disease with iFR / FFR

in multivessel disease PCI patients (SYNTAX II)

Data from Hospital Clinico San Carlos, Madrid, Spain.

37% 74%Eligible patients

For 3VD-PCI according to

ESC guidelines (%)

Angiography driven PCI

Ischemia-driven PCI

Reclassification of multivessel disease with iFR / FFR

in multivessel disease PCI patients (SYNTAX II)

Data from Hospital Clinico San Carlos, Madrid, Spain.

SYNTAX II centres and enrolment / November 2014

Conclusions

• SYNTAX II will explore the benefit of contemporary state-

of-the-art PCI in MVD.

• The study will provide information on how improvements

on stent platform (thinner struts, biocompatible alloys,

open cell design) and eluting matrix (controlled

biodegradation, abluminal distribution) influence

outcomes in this complex patient subset

Muchas gracias por su atención