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Boston Scientific Corporation:
DES Bioabsorbable Technologies
Keith Dawkins MD FRCP FACC FSCAI
Global Chief Medical Officer
Executive Vice President
Boston Scientific Corporation
Conflicts of Interest
Boston Scientific Corporation
Employee
Stockholder
DES Polymer Considerations
Purpose of the Polymer
Provides mechanically stable matrix for drug
Modulates drug release into vessel wall
Polymer has no function after drug release is
complete
All polymer coatings have potential to be
damaged
Damaged durable polymers are permanent
Potential Issues with Durable Polymer DES
Safety
Efficacy
Late / very late stent thrombosis
Higher risk in certain patient populations
Potentially require long-term DAPT
Chronic inflammation with neoatherosclerosis
Constant irritant may lead to late restenosis
Diminished efficacy in diabetic populations
SYNERGY™ Stent: Design Characteristics
SYNERGY
Everolimus
PLGA
Ultrathin Abluminal,
Bioerodable Polymer
(Rollcoat Technology)
Element Stent
Element Stent Platform
Bioerodable PLGA polymer is only
applied to the abluminal surface of the
stent
Abluminal delivery of Everolimus
Maximum abluminal coating thickness
4μm
Drug and Polymer gone ~ 3 months
Enhanced Stent geometry
Reduced Stent Profile
Laser-cut hypotube
SYNERGY™ Stent Platform
Stent Architecture
Visibility
PROMUS Element™ 81µm
PROMUS
Element™
SYNERGY™
SYNERGY™ 74µm
PROMUS Element & SYNERGY Stent Designs
Similarities
Platinum Chromium
(PtCr) Alloy
Radial Strength &
Visibility
SYNERGY Design Modifications
Strut Thickness
Connector Angle
Peak Radius
Additional End Connectors
Improvements
Crimping Profile
Flexibility
Conformability
Longitudinal Robustness
Strut Thickness (µm)
Comparative Strut Thickness
SYNERGY (360 days)
BVS
150µm
BioMatrix
Flex
120µm
Resolute
Integrity
89µm
PROMUS
Element
81µm
XIENCE V
81µm
Thinner struts are associated with more rapid healing
SYNERGY
74µm
I
I
0
100
I
I
200 300
BVS
XIENCE/PROMUS
BioMatrix Flex
RESOLUTE Integrity
SYNERGY
Bare Metal Stent
Relative Drug & Polymer Weight
//
I
I
I
I
400
500
600
700
/
/
I
I
I
7,700
7,800
7,900
Coat Weight (µg) per 16 mm Stent
SYNERGY Stent Polymer Coating Microstructure
PLGA Polymer
Everolimus Drug
Stent Strut
SEM of coating (x5000 magnification)
BSC Internal Data
Time Course for Drug & Polymer Dissolution
3
6
Drug
Polymer
6
6
9
10
12
3
Time (Months)
Vascular Response in Healthy Swine Model
OMEGA™ Stent
SYNERGY™ Stent
Similar vascular response to SYNERGY™ & OMEGA™ (BMS)
30 Days
90 Days
180 Days
360 Days
Wilson GJ: J Am Coll Cardiol 2011;57:E1661
Cellular Response to Platinum Chrome
Platinum Chrome vs. PVDF
Less Platelet Adhesion
Less Platelet Aggregation
More Strut Coverage
More mature & functioning
Endothelium
Inflammatory potential similar
between Platinum Chrome &
PVDF
Garanich JS: J Am Coll Cardiol 2011;58:B126
Tellez A: J Am Coll Cardiol 2012;60:B187
SYNERGY Stent: Clinical Trials
EVOLVE FHU
EVOLVE II
First Human Use Trial. 291 patients. PROMUS Element vs.
SYNERGY vs. SYNERGY Half-Dose (1:1:1). Primary
Endpoint: 6 month Late Loss + Composite Safety @ 30 days
Global IDE Trial. 1684 patients, 150 sites, 19 countries .
PROMUS Element Plus vs. SYNERGY (1:1) single-blind
trial. Primary Endpoint: 12 month TLF
EVOLVE II QCA
Quantitative Angiography. 100 Patient Registry, 10-15 sites
(Australia, Japan, New Zealand, Singapore).
Primary Endpoint: 9 month in-stent Late Loss
EVOLVE China
China regulatory approval trial (SFDA). 400 patients, up to 15
sites. PROMUS Element vs. SYNERGY (1:1) Primary
Endpoint: 9 month Late Loss
EVOLVE DAPT
Prospective, Multi-center, Global, double-blind RCT: 3
months vs. 12 months DAPT. 9000 patients.
Primary Endpoint: Cardiac Death/ MI
EVOLVE Trial Results (6 months)
Late Loss Distribution
Late Loss at 6 months
In-Stent Late Loss (mm)
p=0.56
Late Loss Distribution (%)
100
p=0.19
Percentile
80
60
40
20
PROMUS
Element
SYNERGY
SYNERGY
Half-Dose
0
-0.5
-1.0 -0.5
0.0
0.0
0.5
0.5
1.0
1.0
1.5
1.5
2.0
2.0
Observed Value
Non-inferiority is proven because the upper 95.2% confidence bound of
the difference in 6-month late loss is <0.20 for both SYNERGY stents
Meredith IT: J Am Coll Cardiol 2012;59:1362–1370
EVOLVE Trial Results (6 months)
Safety & Efficacy at 6 months
Late Loss at 6 months
p=0.19
Cardiac Death = 0% (All Groups)
Q-MI = 0% (All Groups)
Stent Thrombosis = 0% (All groups)
Patients (%)
Late Loss (mm)
p=0.56
PROMUS
Element
SYNERGY
SYNERGY
Half-Dose
Non-inferiority is proven because the upper 95.2% confidence bound of
the difference in 6-month late loss is <0.20 for both SYNERGY stents
Meredith IT: J Am Coll Cardiol 2012;59:1362–1370
EVOLVE Trial Results (12 months)
Patients (%)
PROMUS Element (n=98)
SYNERGY (n=94)
SYNERGY Half-Dose (n=99)
Components of TLF
Verheye S: Presented at EuroPCR 2012
EVOLVE II Study Design
SYNERGY™ Stent Pivotal Trial
1,954-2,006 patients with
atherosclerotic native coronary lesions
≤ 34 mm in length, RVD ≥2.25 mm ≤ 4.0, %DS ≥ 50
Up to 3 lesions in 2 vessels
(excludes LM disease, CTO, ISR, STEMI)
Randomized Cohort (RCT)
Up to 160 global sites
PROMUS Element™
Plus Stent
N=842
SYNERGY™
Stent
N=842
RCT Design
Multicenter, Noninferiority trial
Single-blind, 1:1 randomization
Primary Endpoint: TLF (CD, TV-MI, or TLR) at 12 months
Follow-up: 30d, 6m, 12m, 18m and annual 2-5 years
PK
Substudy
SYNERGY™
Stent
N=20-30
Diabetes
Substudy
SYNERGY™
Stent
N=250-292
SYNERGY™ vs. BVS
SYNERGY™ (BSC)
BVS (ABT)
+++
±
Strut Thickness
Thin (74µm)
Thick (150µm)
Radial Strength
+++
+
Fracture Resistance
+++
±
Visualization
+++
±
Ability to Post-Dilate
+++
-
Full Matrix
+++
-
Low Drug Load
+++
+
Low Polymer Load
+++
+
Short Time to Polymer
Dissolution
+++
+
Low Particulates
+++
+
Normal Vessel Function
?
±
Shorter DAPT
?
-
Acute Performance
The Burden of Stent Thrombosis...
Thrombus
Cost
DAPT
Hemorrhage
Relative Cost (DES Stent vs. DAPT)
US Dollars ($)
7.1%
13.3%
23.5%
60.6%
Assumptions: Cost of Aspirin 81mgs = US$ 0.05
Cost of DES = US$ 1600 (MRG Data, September 2012)
Cost of Clopidogrel 75mgs = US$ 2.80 (www.pharmacychecker.com).
Conclusions
Long term durable polymer exposure is potentially undesirable
The SYNERGY™ Stent is a next generation bioabsorbable polymer
technology with unique properties:
Polymer gone shortly after drug elution is complete at 3 months
Parallel, synchronous drug release and polymer absorption
Ultra-thin abluminal coating and lower polymer load than previous technologies
Presence of drug in arterial tissue throughout entire course of polymer
degradation to promote optimal healing
12-month safety and efficacy data from the EVOLVE Trial support positive
clinical performance
Bioabsorbable polymer DES may improve late outcomes (reduce late/very
late ST), minimize DAPT dependency, and enhance healing vs. durable
polymer DES. Further confirmatory trials are ongoing