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A Unique Approach to
Creating a Polymer Free Stent
The Medtronic Drug Filled Stent Program
Josiah N. Wilcox, Ph.D.
Chief Scientific Officer
Coronary and Renal Denervation
Medtronic CardioVascular
CRT 2013
February 25, 2013
Within the past 12 months, I or my spouse/partner have
had a financial interest/arrangement or affiliation with the
organization(s) listed below.
Affiliation/Financial Relationship
Major Stock Shareholder/Equity
Full Time Employee
Company
• Medtronic, Inc.
• Medtronic CardioVascular
Integrity™ and Resolute Integrity™
A New Standard in Stent Design and Manufacturing
Conventional Stent Design
Medtronic Modular Design
Vs.
Slotted Tube
Modular Design
Medtronic’s Continuous Sinusoid Technology
Sinusoidal Formed Wire
Helical Wrap
Laser Fused
Integrity Platform
Continuous Flexibility Due to Unique Sinusoidal Design
DES:
“Box Car” or Coupler
Continuous Sinusoid
115° Bend
Sinusoidal Formed Wire
Helical Wrap
Laser Fused
Resolute Integrity Improves Deliverability
Superior Deliverability*
100
86
Average Push Force (gf)
80
70
60
69
50
Lower is Better
90
40
30
20
20
10
0
Promus Element DES
2.50 mm x 20 mm
Xience Prime DES
2.50 mm x 18 mm
DES
* Based on 3D tracking bench test data on file at Medtronic, Inc.
Resolute Integrity DES
2.50 mm x 18 mm
Continuous Sinusoid Technology
The Next Revolution in Stent Technology
Enabling designs that
could not be
attempted in the past
Bare Metal Stents
Integrity
S10/Core
Wire
New Alloys
CAUTION: Design concepts not approved for sale or clinical use
Drug-Filled Stent
Drug-Eluting Stents
Resolute
Integrity
S10 DES
Platforms for next gen DES
coatings
•
•
•
•
BioLinx (Resolute)
PC Technology (Endeavor)
Bioabsorbable polymer
Nanoporous
S10 DES
Core wire stent with enhanced deliverability, radiopacity, and size matrix
Attribute
Description
Deliverability
Targeted 10-15% Improvement over Resolute Integrity
Radiopacity
Increased due to core wire technology
Expanded Size
Matrix
New 2.0, 4.5-5.0mm diameters and long length (34 and 38 mm)
sizes at 2.25-2.75 diameters
ML-8 (Xience)
Improved Deliverability
and Radiopacity
Omega (Element)
S10
Integrity
Core wire design
featuring thinner
struts than
Resolute Integrity
CAUTION: Design concepts not approved for sale or clinical use
Deliverability – Animal Model
3.0 x 18mm blinded, pairwise testing
Bench testing also showed a 27% improvement in trackability
Drug Filled Stent (DFS) Technology
Polymer Free Drug Delivery
Innovative DES design
• Essentially a BMS surface
• Designed to address drug carrier issues
such as:
 Polymer biocompatibility
 Inflammation upon polymer degradation
 Surface coating durability
 Enables use of new drugs without extensive
development efforts
Elution Holes
CAUTION: Design concepts not approved for sale or clinical use
Drug Filled Stent (DFS) Technology
Core Wire Construction is sacrificial
Core Material
Co Alloy Shell
CAUTION: Design concepts not approved for sale or clinical use
Laser Hole Drilling
•
•
•
•
Facilitate drug filling and elution
500 – 5000 holes per stent (18 mm)
Variable hole diameter and shape
Automation
– Throughput
– Reliability
CAUTION: Design concepts not approved for sale or clinical use
Drug Filled Stent (DFS) Technology
Elution Hole Drilling – The Present and Future
CAUTION: Design concepts not approved for sale or clinical use
Drug Filled Stent (DFS) Technology
De-Coring Process
Etching Gas +
Sacrificial Core
Vapor Phase Etched Core
(sublimates)
CAUTION: Design concepts not approved for sale or clinical use
Drug Filled Stent (DFS) Technology
Radial Strength Structural Analysis
CAUTION: Design concepts not approved for sale or clinical use
Drug Filled Stent (DFS) Technology
Radial Strength Structural Analysis
CAUTION: Design concepts not approved for sale or clinical use
Drug Filled Stent (DFS) Technology
Stress Distribution Structural Analysis
Driver
CAUTION: Design concepts not approved for sale or clinical use
Drug Filled Stent
Drug Filled Stent (DFS)
CAUTION: Design concepts not approved for sale or clinical use
DFS Deliverability Performance
Summary- 3.0x18mm Size
• Track gain over Resolute Integrity
• Push gain over Resolute Integrity
• Sub 1mm Crossing Profile
CAUTION: Design concepts not approved for sale or clinical use
Radiopacity
DFS, no drug
BMS
CAUTION: Design concepts not approved for sale or clinical use
Drug Filled Stent (DFS) Technology
Possible Elution Mechanism
CAUTION: Design concepts not approved for sale or clinical use
Drug Filled Stent (DFS) Technology
Controllable Elution – In Vitro
60%
50%
DFS Prototype Elution Comparison
% Eluted
70%
Standard non-polymeric elution
Design 1
Design 2
40%
Design 3
Design 4
30%
Design 5
20%
Design 6
Resolute
10%
0%
Time
In vitro testing suggests a variety of elution profiles possible
CAUTION: Design concepts not approved for sale or clinical use
Multiple Elution Profiles Possible
Pre-Clinical Elution
100%
90%
% Drug Remaining In Stent
80%
70%
60%
50%
40%
Resolute
30%
20%
Xience
10%
0%
0
10
20
30
40
50
Days
CAUTION: Design concepts not approved for sale or clinical use
60
70
80
90
100
Multiple Elution Profiles Possible
Pre-Clinical Elution
100%
90%
% Drug Remaining In Stent
80%
Resolute
70%
Xience
60%
DFS 1
50%
DFS 2
40%
DFS 3
30%
DFS 4
DFS 5
20%
10%
0%
0
20
40
60
Days
CAUTION: Design concepts not approved for sale or clinical use
80
100
Distribution of drug in the artery wall
DFS vs Resolute in porcine coronary arteries
CAUTION: Design concepts not approved for sale or clinical use
Drug Filled Stent
28 day histology porcine coronary arteries
DFS (No Drug)
CAUTION: Design concepts not approved for sale or clinical use
DFS-1
Drug-Filled Stent – Morphometric Data
28-Day Porcine Coronary Arteries
CAUTION: Design concepts not approved for sale or clinical use
Conclusions
Extended drug elution can be achieved in a polymer free stent
– Variable elution kinetics possible in vivo
– Clinically relevant drug in tissue levels remain constant for 60 - 180 days
after implantation depending on protypes chosen
– DFS implants result in a significant inhibition of neointimal development
compared to BMS controls
– DFS show excellent healing by 28 days
• Low inflammation (equivalent to BMS)
• Residual fibrin was found associated with DFS with drug only
(marker for drug action)
• 100% endothelialization
• Growth of SMC into the DFS drug lumen
The lack of inflammation and complete healing suggests DFS
may be appropriate for a wide variety of patients with
potential for enhanced safety and outcomes
CAUTION: Design concepts not approved for sale or clinical use