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Innovation in Stent Platform/Structure and
Clinical Impacts
Alan C. Yeung, MD
Li Ka Shing Professor of Medicine
Chief, Division of Cardiovascular Medicine
Stanford University School of Medicine
Conflict of Interest
• Abbott Medical Advisory Board
• Medtronic Coronary Scientific Advisory
Board
• Boston Scientific Executive Physician
Council
Stanford
Three Clinical Needs in New DES
• Late Stent Thrombosis
• Restenosis of DES
• DAPT needs
Stanford
Stanford
Stanford
Three Clinical Needs in New DES
• Late Stent Thrombosis
• Restenosis of DES
• DAPT needs
Stanford
Durability of Antirestenotic Efficacy
Cumulative LLL in ABSORB Cohort B
and Patients Treated With EES
TLR with Everolimus-Eluting Stent
Through 3 Years – ISAR TEST 4
16
(N=652)
%
12.8
12
8.8
9.9
8
4
0.5
0
30 days 1 year
Serruys PW. Presented at TCT 2011
2 years 3 years
Byrne R et al. J Am Coll Card 2011; 58:1325-31
Etiology of DES events beyond 1 year
Very late thrombosis and restenosis
Possible causes
1. Uncovered stent struts (thrombosis)
2. Persistent stimulation of SMCs, from adherent fibrin
and/or loss of normal vessel curvature
3. Abnormal shear stress from protruding struts and/or
loss of cyclic strain relief (compliance mismatch)
4. Chronic inflammation due to late foreign body
reactions and polymer hypersensitivity
5. Positive remodeling with strut malapposition
6. Strut fracture
7. Neoatherosclerosis
Technische Universität München
Polymer Coatings and Arterial Healing
• Most clinically effective durable polymer DES
coatings contain methacrylate polymer e.g. PBMA
(Cypher SES, Xience EES, Resolute ZES)*
• PBMA degrades to the
monomer methacrylic
acid which has proven
cellular toxic effects#
*Cypher, Xience, Resolute Product information;
# Curcio
et al. Circulation Journal 2011
Stent designs tested (n=15 for each design)
10
Bend cycles to fracture for 6 designs
P<0.001
10,000,000
NS
Bend Cycles (log scale)
P<0.001
1,000,000
100,000
10,000
1,000
Biomatrix
Flex
Vision
Multi-Link 8
n=15
n=15
n=15
Element
Premier
Integrity
n=15
n=15
n=15
Ormiston EuroIntervention in press
11
Fractures were most commonly in connectors especially
curved parts of connectors
Biomatrix
Flex
Vision
ML8
12
Polymer damage as well as strut fracture
• When DES struts fracture, there is polymer damage too
• May influence local inflammation and restenosis
• May contribute to neoatheroma
Polymer damage
13
Neoatherosclerosis: Transformation of Neointimal
Hyperplasia to Necrotic Core in BMS and DES
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%
Kang SJ et al. AJC 2010;106:1561-1565
57-mo BMS
%NC 57%
%DC 15%
Stanford
Three Clinical Needs in New DES
• Late Stent Thrombosis
• Restenosis of DES
• DAPT needs
Stanford
RESOLUTE Pooled
Timing of Permanent Discontinuation and ST through 3 years
There were only 2 events out to 3 years among patients permanently discontinuing
DAPT after completing one month of DAPT.
There were no new ST events between 24 and 36 months.
Timing of Permanently Discontinued DAPT
And ST Through 3 Years
10.0%
Subsequent ST
(ARC Def/Prob) (%)
8.0%
6.35%
6.0%
4.0%
2.46%
2.0%
0.0%
Not Permanently
Discontinued
# of pts at risk
at baseline
# of events
Permanently
Discontinued
0-1 Month
0.00%
0.11%
0.00%
Permanently
Discontinued
1-12 Months
Permanently
Discontinued
12-24 Months
Permanently
Discontinued
24-36 Months
1789
63
594
1806
644
44
4
0
2
0
The never interrupted group includes patients who interrupted only after an ST event.
For OMA Distribution Only. Trademarks may be registered and are the property of their respective owners. © 2013 Medtronic, Inc. All Rights Reserved. 10116744DOC_1A 10/2013
XIENCE Demonstrates 0% Stent Thrombosis Rate
1
After DAPT Interruption from 3 to 12 Months
1 Palmerini,
T. Stent Thrombosis and DAPT Interruption in XIENCE V Real-World Patients. PCR 2012.
patients with no DAPT Interruption except possibly after Stent Thrombosis though 365 days.
Patients should follow physicians’ guidance for utilization of dual anti-platelet therapy following stent implantation.
2 Including
Abbott Vascular Confidential, for advisory board
purposes only. Do not distribute, reproduce or excerpt.
©2013 Abbott. All rights reserved.
18
3 Approaches to Improve Late DES
Outcomes
1. Metallic DES with bioabsorbable polymers
2. Metallic DES, polymer-free
3. Bioresorbable vascular scaffold (BVS)
Evolution of DES Technology
First Gen
Second Gen
TAXUS
Liberte
Resolute
Integrity
Xience
Xpedition
Promus
PREMIER
96 µm
89 µm
81 µm
81 µm
14µm/side
6µm / side
8µm / side
8µm / side
Durable
Polymer
Stents
Cypher
TAXUS Express
Strut Thickness
140 µm
132 µm
Coat Thickness
7µm / side
16µm/side
Biomatrix
Nobori
Synergy
Strut Thickness
120 µm
125 µm
74µm
Coat Thickness
10 µm
20 µm
4 µm
Bioabsorbable
Polymer
Stents
First Generation Future Technologies
Fully
Bioresorbable
Stents
BVS
ELIXIR DESolve
DREAMS II
Polymer
Free
Stents
BIOFREEDOM
Drug Filled
Stent
Strut Thickness
150 µm
150 µm
150 µm
112
86
Coat Thickness
3 µm / side
<3 µm / side
8 µm / side
NA
NA
Platelet Accumulation on Stent Surface
PVDF Durable Polymer vs. Metallic Surfaces
*
*
*
Eppihimer M, Granada JF, TCT2012
Total Stent Inflammatory Area
Bioabsorbable vs. Durable Polymer DES
Inflammation Area (mm2)
Inflammation at 180 Days in Familial Hypercholesterolemic Swine Model
1.6
* p<0.05 vs BMS & SYNERGY
1.4
0.70*
1.2
0.43*
1.0
0.8
0.6
0.4
0.08
0.14
0.2
0.0
OMEGA BMS
SYNERGY
Resolute Integrity Xience Prime
Granada JF, EuroPCR 2014
Stent Surface and EC Coverage
Abluminal vs. Conformal Polymer
100
% Endothelial Cell (EC) Coverage at 21 Days in Cell Assay
80
60
40
20
89
88
0
BMS
Abluminal
Bioabsorbable
PLGA
58
55
Conformal
Bioabsorbable
PLGA
Conformal
Durable PVDF
Mike Eppihimer, PhD, EuroPCR 2014
89 RCTs with 85,490 patients
Palmerini et al. JACC 2014;63:299-307
