syntax ii, innovación científica en investigación biomédica con el stent farmacoactivo synergy ...
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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
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