A drug-eluting stent is a peripheral or coronary stent placed into narrowed, diseased peripheral or coronary arteries that slowly releases a drug to block cell proliferation. This prevents fibrosis that, together with clots, could otherwise block the stented artery, a process called restenosis

1. DRUG ELUTING CORONARY STENT
DIBYASUNDAR MAHANATA

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.

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).

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.

6. PALMAZ-SCHATZ
 Balloon expandable;
slotted tube
 316 L stainless steel

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.

8. STENT SELECTION

9. STENT SELECTION-PERFORMANCE &
EASE OF USE

10. STENT SELECTION-GOOD ACUTE
ANGIOGRAPHIC RESULTS

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)
 Geometrical configurations/design (mesh structure, coil,
slotted tube, ring, multi-design)
 Addition to stent (grafts, radio-opaque markers,coatings)

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.

14. MATERIALS
 Corrosion resistance
 Biocompatibility
 Adequately radio-opaque
 Create minimal artifacts during MRI

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)

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).

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

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

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

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

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

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.

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.

26. COIL VS TUBE

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.
.

28. SLOTTED TUBE VS. MODULAR (TUBULAR)

29. MODULAR DESIGN

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.

33. CYPHER STENT BY CORDIS

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

35. OPEN CELL DESIGN

41. STENT DESIGN IMPACTS DRUG
DELIEVERY

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

43. NUMBER OF STRUTS
 More struts vs. less
 Less struts induce less chance of restenosis
compare to more struts.

45. 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

46.  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.

47. 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

50. 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.

51. SQUARE VS. ROUND STRUT CROSS-SECTION

52. 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.

53. ELEMENT OF STENT DESIGN- BALLOON
OVERHANG

54. 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)

55.  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)

57. THERAPEUTIC AGENTS
 Sirolimus (Rapamycin) m TOR inhibitor
 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

58. PACLITAXEL AND ITS ANALOGUES
 Paclitaxel
 Promoting tubulin polymerization and cell cycle arrest
between G2 and M phase
 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

59. OTHERS
 Tacrolimus
 Pimecrolimus
 Curcumin
 Resveratrol
 CD 34 antibody
 Anti-VEGF

60. 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

61. 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.

64. COMMONLY USED CORONARY
STENTS IN CLINICAL PRACTICE

65. XIENCE FAMILY OF STENTS
Stent Manufactu Drug Base
rer
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

66. 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

67. 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
gradestainless
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
gradestainless
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
alternatinglong
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

68. Stent
Coracto
Manufactur
er
Alvimedica
Drug
Rapamycin
Base
Stainless
steel
Form/Design
Tubular,opencell
design
Polymer
Ultrathin
polymer layer
absobes 100%
in 10-12 week
Diameter
2.5,2.75,2.90,3
.00,3.5,4.0
Length
9,13,17,21,26,
28,32
Coroflex B.Braun Paclitaxel Stainless Multicellular ring P matrix- 2.5,2.75,3.0,3. 8,13,16,19,25,
please 1μg/cumm steel design,Hybrid
Superb
polysulfone
coating
5,4.0 28,32
radioopacity
Cypher cordis Sirolimus
100%drug
release with in 1
month
Stainless
steel
Tubular,laser
cut,sinusoidal
pattern,closedcell
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

69. 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
Strutthickness
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 upto40-
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

70. 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

71. 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,
tubularstent
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 Sirolimus Co Cr Hybrid Biocompatibl 2.25,2.50,2.7 13,18,23,28,3
concepts,UK S shaped e,biostable 5,3.0,3.25,3.5 3,38
articulations polymer,drug 0,4.0
release upto
30 days
Biomime Meril Life
Sciences,
India
Sirolimus
1.25μgm/sqm
m of stent
surface,30 day
elutionkinetics
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

72. Stent Manufactur
er
Drug Base Form/Desi
gn
Polymer Diameter Length
ACTIVE& IHT Paclitaxel Stainless steel Open P5 - 2.0,2.25,2.5,2. 9,14,18,19,23,
ACTVE small cell,tubular Biocompatible 75,3.0,3.5,4.0, 28,36
polymer 4.5
EVERLITE Unimark Everolimus Co Cr Open Biodegradable 2.25,2.5,2.75,3.0 8,13,16,19,24,29
remedies Low drug dose
1.2μg/sqmm
cell,Sinosoidal
strut
design,alternativ
,3.5,4.0,4.5 ,32,37,40
e S link,ultrathin
strut 65μm
Flexy Rap Lancer medical Rapamycin Co Cr Open Biodegradable 2.25,2.5,2.75,3.0 7,10,13,15,17,20
technology 1μg/sqmm cell, Radial star
segments
polymer ,3.5,4.0 ,24,28,33,38,42
combined with
flexible
links,Strut 65μm,
INDOLIMUS
Ce mark
Sahajanand
medical
sirolimus Co Cr Opencell,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

76. THANKS