2. BACKGROUND
The introduction of angioplasty led to the
development of a completely new approach to treat
CAD.
Until 1994, the percutaneous transluminal coronary
angioplasty (PTCA) was the alone treatment for
coronary artery disease.
However, the incidence of restenosis of coronary
arteries was an important problem, necessitating
repeated interventional procedures in 30% of
patients treated with PTCA alone.
NEJM 1994;331:489-95
3.
4. Coronary artery stents were developed to provide a
metal scaffolding for the angio-plastied vessel, in an
attempt to limit negative re-modelling.
Sigwart et al first reported the efficacy of stents in
reducing restenosis rates in 1987.
By 1994, the Food and Drug Administration (FDA)
had approved two stents (Gianturco-Roubin stent
and the Palmaz- SchatzTM stent).
Journal of Invasiv Cardiology.2001;13:634-639
5. GIANTURCO-ROUBIN II
Flat wire coil attached
to a single longitudinal
strut
316 L stainless steel
The first coronary stent
approved by the FDA in
June 1993.
J. clinical pathology.2005,aug;58(8):795-804
7. The wide acceptance of coronary stenting was based on
the results of the BElgian NEtherlands STENT
(BENESTENT) and the STent REStenosis Study
(STRESS) trials, which showed the superiority of
stenting over balloon angioplasty.
After the wide acceptance of coronary stents the primary
concern of stent development is the need to reduce
device profiles and to increase flexibility to facilitate safe
delivery.
N Engl J Med,1994;331:489-95.
12. TYPES OF STENTS
Mechanism of expansion (self-expanding or balloon-
expandable)
Materials (stainless steel, cobalt-based alloy, tantalum,
nitinol, Pt,Ir,Cr, inert coating, biodegradable)
Forms (sheet, wire or tube)
Manufacturing methods (laser cut, water-jet cutting, photo-
etching)
Geometrical configurations/design (mesh structure, coil,
slotted tube, ring, multi-design)
Addition to stent (grafts, radio-opaque markers, coatings)
Min Invas Ther & Allied Technol
2002;11:137-47.
13. STENT GEOMETRIC DESIGN
MECHANISM OF EXPANSION
Balloon-expandable stents
The stent is pre-mounted on a balloon and the inflation
of the balloon plastically expands the stent with respect
to the balloon diameter.
Self-expanding stents- The smart material auto expands
to a calculated size.
Journal of invasive cardiology 1995;7:127-
134
15. STENT PLATFORMS
STENT MATERIALS- NON DEGRADABLE MATERIAL
316L stainless steel-
Excellent mechanical properties and corrosion
resistance
Ferromagnetic nature and low density make it a
non-MRI compatible
Poorly visible fluoroscopic material
First generation DESs, Cypher (sirolimus-eluting
stent, Cordis, Warren, NJ) and Taxus (paclitaxel-
eluting stent, Boston Scientific, Natick, MA)
JACC 1996;27:53
16. CO-CR
Superior radial strength and improved radiopacity
Thinner stent struts
The second generation DES, Xience V (everolimus-
eluting stent, Abott Vascular, CA) and Endeavor
(zotarolimus-eluting stent,Medtronic Vascular,
Santa Rosa, CA).
JACC 1996;27:53
17. TA- TANTALUM
Excellent corrosion resistant material
Coated on 316L SS to improve corrosion properties
and biocompatibility
High density and non-ferromagnetic properties
Fluoroscopically visible and MRI compatible
Higher rates of recoil- poor mechanical properties
JACC 1996;27:53
18. TI
Excellent biocompatibility and corrosion resistance
Low tensile strength and ductility
Ti alloys in combination with Ni-Ti
Ti-nitride oxide coating on 316L SS
JACC 1996;27:53
19. NI-TI
Good biocompatibility, radial force and shape
memory
Coated by some materials such as polyurethane, Ti
nitride and polycrystalline oxides to improve the
corrosion resistance
Inadequate visibility under fluoroscopy
American J of cardiology.2008;86:1073-
1079
20. PT-IR
Pt-Ir alloy of 90% platinum and 10% iridium
Excellent radiopacity and a reduction in both
thrombosis and neointimal proliferation with less
inflammatory reactions
Recoiling percentage was much higher (16%) than
the 316L SS stents
Journal of invasive cardiology 1995;7:127-
134
21.
22. BIODEGRADABLE METALLIC MATERIALS
Pure Fe
Oxidation of Fe into ferrous and ferric irons
Mg alloys
There are two Mg alloys, AE2153 and WE4357,
used for making stents
Radiolucent
Biomaterials.2006;27:1728-1734
23. RATIONAL FOR BIODEGRADABLE STENTS
Metal stent drawbacks
Cause permanent physical
irritation
Risk of long term endothelial
dysfunction and chronic
inflammation
Metal have thrombogenic
properties
Inability for the vessel to
restore its a normal
physiology
Biodegradable stent advantages
May eliminate early and late
complications of bare-metal
stents
Restore the vasoreactivity
Allow a gradual transfer of the
mechanical load to the vessel
Higher capacity for drug
incorporation and complex
release kinetics
The need for a permanent prosthesis decreases
dramatically 6 months post-implantation
24. STENT DESIGN
On the basis of design, stents can be divided into
three groups: coil, tubular mesh, and slotted tube.
Coil stents are characterised by metallic wires or
strips formed into a circular coil shape
Tubular mesh stents consist of wires wound
together in a meshwork, forming a tube.
Slotted tube stents are made from tubes of metal
from which a stent design is laser cut.
Eur Heart J 1997;18:1536–47
25. COIL VS. TUBE
Coil design had greater strut width with gaps and
fewer or no connections between struts
The strut width is greater; there are gap between
struts, and no connections between struts which
give it more flexibility.
However, the design lack radial strength, and the
wide gap allow tissues to dangle.
Singapore Medical Journal, 2004.
27. As a result, coil design has become obsolete and
replace by the more superior in radial strength, the
tube design.
In tubular, there are two type of specification, a
slotted tube and modular tube.
Singapore Medical Journal, 2004.
31. SLOTTED TUBE VS. MODULAR (TUBULAR)
Slotted tube stents resisted restenosis more than
the modular stents (22.1% vs 25.2%)
Slotted tube- Closed cell design, and open cell
design
32. CLOSED CELL
Sequential ring construction
All Internal inflection points of the structural
members are connected by bridging elements.
Regular peak-to-peak connections.
Optimal scaffolding and a uniform surface,
regardless of the degree of bending.
Less flexible than a similar open-cell design.
Ann Ist Super Sanita 2007;43,no1:89-100
34. OPEN CELL
Some or all the internal inflection points of the
structural members are not connected by bridging
elements.
Periodic peak-to-peak connections, peak-to-valley
connections, and mid-strut to mid strut connections
The unconnected structural elements contribute to
longitudinal flexibility.
Ann Ist Super Sanita 2007;43,no1:89-100
42. LENGTH & DIAMETER OF STENT
Long vs. Short
Stent length is associated with restenosis rate and
clinical events (mainly target lesion revascularization)
Short stent has lower cases of restenosis than long
stent.
Wide vs. Narrow
The wide diameter stent is more favorable than the
narrow one
European Heart Journal 2001;22:1585-
1593
43. NUMBER OF STRUTS
More struts vs. less
Less struts induce less chance of restenosis
compare to more struts.
47. STRUT THICKNESS
Although the immediate stent performance may be
improved by increasing strut thickness (which increases
radiovisibility, radial strength and arterial wall support)
excessive strut thickness, on the other hand, may impart
more vascular injury, trigger more intimal hyperplasia,
and engender a higher risk for restenosis than thinner
struts.
Strut thickness was observed to be an independent
predictor of in-stent restenosis
ISAR STEREO study(Circulation 2001;103:2816-21)
ISAR-STEREO-2 trial(J Am Coll Cardiol 2003;41:1283-8.)
48. In an effort to further reduce strut thickness while
maintaining adequate radiovisibility and radial
strength, novel metallic materials such as cobalt-
chromium alloy are being used for the production of
stent.
49. THICK VS. THIN STRUTS
The stents with thinner struts is preferred for the
design of new stents as they can reduce
angiographic and clinical restenosis more than
those with thicker struts
ISAR-STEREO and ISAR-STEREO 2
trials
50.
51.
52. SQUARE VS. ROUND STRUT CROSS-SECTION
The round strut cross-section without corners or
sharp edges is popular at present
Round strut cross-section area is ideal for
smoothness design.
Square strut cross-section area in not recommend
because it interferes with blood flow due to their
sharp edge which can slice blood cells.
Kluwer Academic Publishers 2012
54. ROUGH VS. SMOOTH SURFACE
Smoothness of a stent can affect the performance and
biocompatibily of the stent.
Smooth surface can reduce thrombus adhesion and
neointimal growth.
To obtain smoothness, the stent need to be treated with
acid-pickling and then electrochemical polishing.
The process removes slag which includes depositions
and burrs, formed on the surface of stents due to the
laser cutting production process. Seminars in interventional
cardiology1998;3:139-144
56. DRUG DELIVERY VEHICLES – COATING
POLYMER- DRUG CARRIERS IN DESS
Nonbiodegradable and biodegradable polymers
Non biodegradable polymers
First and the second generation of DESs
The first generation of DES
Cypher - polyethylene-co-vinyl acetate (PEVA)/poly-n-butyl methacrylate
(PBMA)
Taxus - polystyrene-b-isobutylene-b-styrene (SIBS)
The second generation of DES
Xience V – fluoropolymer
Endeavor - phosphorylcholine (PC)
Eurointervention,2005;1:266-272
57. Biodegradable polymers
Polylactic acid (PLA)
Polyglycolic acid (PGA)
Polylactic-co-glycolic acid (PLGA)
NON POLYMER
Titanium–nitric oxide alloy
Microporous stainless steel stent (Yukon, Translumina, Germany)
A nanoporous hydroxyapetite (a biocompatible crystalline derivative of
calcium phosphate) coating
Magnetic nanoparticles (MNPs)
Eurointervention,2005;1:266-272
60. THERAPEUTIC AGENTS
Sirolimus (Rapamycin)
A macrocyclic lactone
Inhibits the migration and proliferation of SMCs
Zotarolimus
The sirolimus analogues
Developed by Abbott laboratories
Extremely lipophilic property and low water solubility
Everolimus
Sirolimus analogue
Immunosuppressive agent
Absorbs to local tissue more rapidly and has a longer celluar residence time and activity
Biolimus
61. PACLITAXEL AND ITS ANALOGUES
Paclitaxel
Promoting tubulin polymerization and cell cycle arrest
Inhibiting the migration and proliferation of SMCs
Coroxane
Nanoparticle albumin bound paclitaxel (nab-paclitaxel)
To improve the solubility
Docetaxel
Semi-synthetic analogue
Better anti-proliferative properties
63. RADIO-OPACITY ENHANCEMENTS
Stainless steel or nitinol - hard to see
fluoroscopically
To improve X-ray visibility, markers are often
attached to the stents.
These additions are typically made from gold,
platinum or tantalum
Electroplating (with gold) is also being used to
enhance X-ray visibility
64. COATINGS
To increase biocompatibility
Heparin was one of the first. Its mode of action is to
reduce the coagulation cascade (and thus possibly the
thrombogenic risk) after the deployment of a stent.
Phosphorylcoline and silicon-carbide have been used in
order to reduce platelet activation and interaction, thus
possibly controlling their adhesion to the stent struts
during the acute phase of stent re-endothelization.
65. Passive coverage has been also shown to be
useful.
Indeed, covered stents have been created, in which
a PTFE layer was put between two stents (Jostent
graft, Jomed) or one stent was covered by a inner
and an outer layer of PTFE (Symbiot, Boston
Scientific)
67. XIENCE FAMILY OF STENTS
Stent Manufactu
rer
Drug Base Form/Desi
gn
Polymer Diameter Length
XIENCE
Xpedition
Abott
vascular
FDA
Approved
Everolimus
100μg/cm2
L-605 CoCr Hybrid cell
Multilink
0.0032" strut
thickness,
laser cut
PBMA
Non erodible
SV-2.25
MV-
2.5,2.75,3.0,3.
25,3.5,4.0
LL
2.5,2.75,3.0,
3.25,3.5,4.0
8,12,15,18,23
,28
33,38
XIENCE V Abott
vascular
FDA
Approved
Everolimus
100μg/cm2
Multi-layer
Coating
MULTI-LINK
VISION CoCr
stent
Hybrid cell
Multilink
0.0032" strut
thickness,
laser cut,
PBMA
Non erodible
2.25,2.5,2.75,
3.0,3.5,4.0
8,12,15,18,23
,28
XINCE
PRIME
Abott
vascular
FDA
Approved
Everolimus
100μg/cm2
Cobalt
Chromium
Hybrid cell
Multilink
0.0032" strut
thickness,las
er cut,
biocompatibl
e fluorinated
copolymer
SV-2.25
MV
2.5,2.75,3.0,
3.5,4.0
LL-
2.5,2.75,3.0,
3.5,4.0
8,12,15,18,23
,28
Same
33,38
68.
69. THE XIENCE XPEDITION EVEROLIMUS ELUTING
CORONARY STENT SYSTEM
(ABOTT VASCULAR) FDA, CE MARK
The drug-coated stent and the balloon expandable
delivery system
22% less force used to deliever than prime.
Ultra low distal seal technology for outstanding
crossability.
Unique 3.25mm diameter for more accurate vessel
sizing.
More flexible multilayered balloon with flatter
compliance.
70. Stent Manufactur
er
Drug Base Form/Desi
gn
Polymer Diameter Length
Promus element
Plus
Boston scientific Everolimus Platinum
Chromium
Tubular open
cell,thin
strut,high radial
strength,good
delieverality &
trackability
Thin, fluorinated
copolymer
matrix for
controlled drug
release (100%
drug elution in
120 days)
2.25,2.5,2.75,3.0
,3.5,4.0
8,12,16,20,24,28
,32,38
Endeavor Sprint Medtronic Zotarolimus-
Eluting
10μg/mm
cobalt-based
alloy (cobalt,
nickel,
chromium, and
molybdenum)
Modular
design,Sinusoid
al form
wire,helical
wrap,laser fused
Phosphorylcholi
ne polymer
2.25,2.5,2.75,3.0
,3.5,4.0
8,12,14,18,22,26
,30,34,38
Resolut Integrity Medtronic Zotarolimus
eluting
cobalt-based
alloy (cobalt,
nickel,
chromium, and
molybdenum)
Modular
design,Sinusoidal
form wire,helical
wrap,laser fused
BioLinx
biocompatible
polymer
2.25,2.5,2.75,3.0
,3.5,4.0
8,12,14,18,22,26
,30,34,38
71. Stent Manufactur
er
Drug Base Form/Desi
gn
Polymer Diameter Length
Taxus Liberte Boston Scientific Paclitaxel
1 μg/mm2
paclitaxel in a
slow release
(SR)*
316L surgical
grade stainless
steel
Sinusoidal ring
modules linked
via curved link
elements
SIBS
[poly(styrene-b-
isobutylene-b-
styrene)], a tri-
block copolymer
(trade name:
Translute)
2.50, 2.75, 3.00,
3.50, 4.00
8, 12, 16, 20, 24,
28, 32
TAXUS Express Boston Scientific Paclitaxel
1μg/mm2
paclitaxel in a
slow release
(SR)
316L surgical
grade stainless
steel
modular ring
strut pattern
consists of two
separate module
designs: short,
narrow
sinusoidal Micro
elements linked
via straight
articulations to
long, wide
sinusoidal Macro
elements
SIBS
[poly(styrene-b-
isobutylene-b-
styrene)], a tri-
block copolymer
(trade name:
Translute)
2.50, 2.75, 3.00,
3.50
8, 12, 16, 20, 24,
28, 32
Taxus Element Boston Scientific Paclitaxel
1.0 μg/mm2
Platinum
Chromium
Sinusoidal ring
modules
consisting of
alternating long
and short
SIBS
[poly(styrene-b-
isobutylene-b-
styrene)], a tri-
block copolymer
2.25,2.50,2.75,3.
0,3.5,4.0,4.5
8,12,16,20,24,28
,32,38
72. Stent Manufactur
er
Drug Base Form/Design Polymer Diameter Length
Coracto Alvimedica Rapamycin Stainless
steel
Tubular,open cell
design
Ultrathin
polymer layer
absobes 100%
in 10-12 week
2.5,2.75,2.90,3
.00,3.5,4.0
9,13,17,21,26,
28,32
Coroflex
please
B.Braun Paclitaxel
1μg/cumm
Stainless
steel
Multicellular ring
design,Hybrid
Superb
radioopacity
P matrix-
polysulfone
coating
2.5,2.75,3.0,3.
5,4.0
8,13,16,19,25,
28,32
Cypher cordis Sirolimus
100% drug
release with in 1
month
Stainless
steel
Tubular,laser
cut,sinusoidal
pattern,closed cell
two non-erodible
polymers:
polyethylene-co-
vinyl acetate
(PEVA) and poly
n-butyl
methacrylate
(PBMA)
2.50, 2.75, 3.00,
3.50
8, 13, 18, 23, 28,
33
73. Stent Manufactu
rer
Drug Base Form/Desi
gn
Polymer Diameter Length
YUKON
Choice 4DES
Translumina,
German
CE mark
Sirolimus Medical
Stainless
Steel, 316
LVM, Surface
containing
micro-pores
1million
pores/sqcm
Balloon marker
material
Platinum /
Iridium
microporous
PEARL
Surface
Strut thickness
0,0034” / 87
μm
Hybrid design
Non
polymeric
Shellac resin
bio
compatible
resin
6 to 8 weeks
release
2.0,2.25,2.50,2
.75,3.0,3.5,4.0
8,12,16,18,21,
24,28,32,40
GEN X Sync MIV
therapeutics
India pvt ltd
Sirolimus Co Cr Open cell,
alternate S
link,uniform
sinusoidal strut
design
Bio resorb
PLLA-poly L
lactic acid
polymer
Ultrathin
coating(3μm)
Drug sudden
release f/b
release upto 40-
50 days.
2.0,2.25,2.50,2
.75,3.00,3.50,4
.0,4.5
8,13,16,19,24,
29,32,37
Supralimus Sahajanand
Medical
Technologies
Pvt Ltd, India
Sirolimus Sainless steel Hybrid biodegradable
drug-
carrier ,50%
drug release in
7 days next
50% in 41days
2.5,2.75,3.0,3.
5
8,12,16,20,24,
2832,36,40
Supralimus-
Core
Sahajanand
Medical
Technologies
Pvt Ltd, India
Sirolimus cobalt-
chromium
Hybrid biodegradable
drug-
carrier ,50%
drug release in
7 days next
50% in 41days
same same
74. Stent Manufactur
er
Drug Base Form/Desi
gn
Polymer Diameter Length
YUKON Choice
PC
Translumina,
German
CE mark
Rapamycin
(Sirolimus)
Release of
sirolimus up to 4
weeks
Medical
Stainless Steel,
316 LVM,
Surface
containing
micro-pores
1million
pores/sqcm
Favours better
endothelialisatio
n
Balloon marker
material
Platinum /
Iridium
microporous
PEARL Surface
Strut thickness
0,0034” / 87 μm
Hybrid design
The
biodegradable
components
polylactide and
shellac
2.0,2.50,2.75,3.0
,3.5,4.0
8,12,16,18,21,24
,28,32,40
75. Stent Manufactu
rer
Drug Base Form/Desi
gn
Polymer Diameter Length
BioMatrix Biosensors
Inc, Newport
Beach, Calif
CE mark
biolimus A9
highly
lipophilic,
semi
synthetic
sirolimus
analogue
(≈15.6 μg/mm
of stent
length)
S-Stent (316
L) stainless
steel stent
with a strut
thickness of
0.0054 inches
(137 μm)
laser-cut,
tubular stent
S-Stent
platform
Open cell,
quadrature
link
Biodegradabl
e,
Polylactic
acid (PLA)
applied to the
abluminal
surface
2.25,2.50,2.7
5,3.0,3.5,4.0
8,11,14,18,24
,28,33,36
Pronova Vascular
concepts,UK
Sirolimus Co Cr Hybrid
S shaped
articulations
Biocompatibl
e,biostable
polymer,drug
release upto
30 days
2.25,2.50,2.7
5,3.0,3.25,3.5
0,4.0
13,18,23,28,3
3,38
Biomime Meril Life
Sciences,
India
Sirolimus
1.25μgm/sqm
m of stent
surface,30 day
elution kinetics
Co Cr Hybrid cell
design
65μm strut
thickness
Biodegradabl
e polymer
2.5,2.75,3.0,3
.5,4.0,4.5
8,13,16,19,24
,29,32,37,40
76. Stent Manufactur
er
Drug Base Form/Desi
gn
Polymer Diameter Length
ACTIVE&
ACTVE small
IHT Paclitaxel Stainless steel Open
cell,tubular
P5 -
Biocompatible
polymer
2.0,2.25,2.5,2.
75,3.0,3.5,4.0,
4.5
9,14,18,19,23,
28,36
EVERLITE Unimark
remedies
Everolimus
Low drug dose
1.2μg/sqmm
Co Cr Open
cell,Sinosoidal
strut
design,alternativ
e S link,ultrathin
strut 65μm
Biodegradable 2.25,2.5,2.75,3.0
,3.5,4.0,4.5
8,13,16,19,24,29
,32,37,40
Flexy Rap Lancer medical
technology
Rapamycin
1μg/sqmm
Co Cr Open
cell, Radial star
segments
combined with
flexible
links,Strut 65μm,
Biodegradable
polymer
2.25,2.5,2.75,3.0
,3.5,4.0
7,10,13,15,17,20
,24,28,33,38,42
INDOLIMUS
Ce mark
Sahajanand
medical
sirolimus Co Cr Open cell,laser
cut,seamless
tube,60 micm
strut thickness
Biodegradable
polymer matrix
2.5,2.75,3.0,3.5 8,12,16,20,24,28
,32,36,40
