New Drug-Eluting Stents Soo-Joong Kim M.D., PhD. Department of Cardiology, Internal Medicine, Kyung Hee University Medical Center

New Drug-Eluting Stents

Soo-Joong Kim M.D., PhD.

Department of Cardiology, Internal

Medicine,

Kyung Hee University Medical Center

Drug-Eluting Stents

• Impressive clinical benefits

• Safety concerns : stent thrombosis

– patient factors

– lesion factors

– stent polymer : focal area for new research & stent

development

3 components of DES

Drug

Polymer Stent platform

The second-generation DES

• more biocompatible polymers

• impressive safety results at medium-term follow-up

• concerns for a nonerodable polymer

– persistent arterial wall inflammation

– delayed vascular healing

precipitating ST and delayed restenosis

New DES

• Development of DES coated with biodegradable polymers.

• attractive combination of controlled drug elution in parallel

with biodegradation of the polymer into inert monomers

• after complete biodegradation

– Only BMS remains

– Reducing long-term risks a/w permanent polymer

• Stents completely free of polymer,

• BMS coated in novel coatings

• Completely biodegradable magnesium and polymeric stents

– completely disappear once vascular healing has taken place.

• Metallic DES with Durable Polymer

Metallic DES with Durable Polymer

• new durable polymer

–new polymer technology

–new antiproliferative agents

–new metal stent platforms


• Endeavor Resolute

– Driver cobalt chromium stent platform

– Biolinx polymer : a blend of 3 different polymers: • the hydrophobic C10 polymer to control drug release

• the biocompatible and hydrophilic C19 polymer

• polyvinyl pyrrolidone (early burst of drug release)

– Delayed drug release

: at least 85% of the zotarolimus released within 60 days,

with the remainder released within 180 days

– match the delayed healing times seen in complex lesions

New polymer technol-ogy

Endeavor Resolute Stent


• 139 pts, multicenter, nonrandomized, FIM – angiographic in-stent late loss of 0.22 mm at 9 M f/up– and respective rates of MACE, TLR, & any ST

: 8.6%, 0.7%, & 0.0% at 12 M f/up

11.6%, 1.6%, 0.0%% at 3-year f/up

• RESOLUTE All-Comers trial– 2,300 pts, – randomized in a 1:1 ratio either R-ZES or the Xience V – At 12-months clinical follow-up, noninferior to EES with re-

spect to the primary clinical end point of target lesion fail-ure, a composite of cardiac death, target vessel MI & clini-cally indicated TLR (ZES 8.2% vs. EES 8.3%, pnoninferiority <0.001)

Endeavor Resolute

Definite or probable ST : 18 (1.6%) vs 8 (0.7%), p=0.05

Definite or probable or possible : 26 (2.3%) vs 17

(1.5%), p=0.17


• Elixir DESyne novolimus-eluting stent (NES)

– Cobalt chromium stent platform

– a durable poly(n-butyl methacrylate) polymer (similar to

Cypher sirolimus-eluting stent)

– a drug coating of novolimus : mTOR inhibitor (metabolite

of sirolimus)

• a similar efficacy to currently available agents

• lower drug dose (NES 5 g/mm of stent length vs. ZES 10 g/mm)

• lower polymer load (polymer thickness <3 μm vs. 4.1 m on ZES)

New antiproliferative agents

Elixir DESyne NES

• 15-pts FIM EXCELLA (Elixir Medical Clinical Evaluation of the

Novolimus-Eluting Coronary Stent System) study

– Angiographic in-stent late loss of 0.31± 0.25 mm

– % volume obstruction IVUS of 6.0 ± 4.4% at 8 M f/up

– No MACE through 12 M & 1 MACE event at 24M

• single-blind, prospective EXCELLA-II study,

– Randomized 210 pts either NES (n = 139) or or ZES (n = 71)

– At 9 M f/up, the primary end point of angiographic in-stent late loss

: 0.11 ± 0.32 mm and 0.63 ± 0.42 mm (pnoninferiority< 0.0001, psuperiority <0.0001)

– During clinical follow-up, no significant differences between stent groups

in the device-orientated composite end point (NES 2.9% vs. ZES 5.6%,

p= .45)

Variables Lesions (n = 15)

Pre-procedure Reference vessel diameter, mm Lesion length, mm Minimum lumen diameter, mm Diameter stenosis, (%)

2.7 ± 0.48.7 ± 3.71.0 ± 0.3

62.5 ± 8.6

4-month follow-up Diameter stenosis, (%) Binary restenosis, (%) Late loss

12.5 ± 13.10

0.15 ± 0.29

8-month follow-up Minimum lumen diameter, mm Diameter stenosis, (%) Lumen loss, mm Binary restenosis, n(%)

2.7 ± 0.418.2 ± 11.80.31 ± 0.25

0

EXCELLA study

IVUS variablesBaselineN= 15 P

4-month follow-upN= 15 P

8-monthFollow-up

N=15p

Vessel Volume (mm3) 251.2 ± 78.8 259.7 ± 86.1 264 + 91.2

Stent Volume (mm3) 130.1 ± 39.7 134.0 ± 39.5 134.5 + 39.4

Lumen Volume (mm3) 129.9 ± 39.7 130.8 ± 40.0 127 + 41.8

NIH Volume (mm3) N/A 3.2 ± 2.8 7.5 ± 3.9

% Stent Obstruction N/A 2.7 ± 2.7 6.0 ± 4.4

% volume obstruction IVUS of 6.0 ± 4.4% at 8 M f/up

• 15-pts FIM EXCELLA (Elixir Medical Clinical Evaluation of the

Novolimus-Eluting Coronary Stent System) study

– Angiographic in-stent late loss of 0.31± 0.25 mm

– % volume obstruction IVUS of 6.0 ± 4.4% at 8 M f/up

– No MACE through 12 M & 1 MACE event at 24M

• single-blind, prospective EXCELLA-II study,

– Randomized 210 pts either NES (n = 139) or or ZES (n = 71)

– At 9 M f/up, the primary end point of angiographic in-stent late loss

: 0.11 ± 0.32 mm and 0.63 ± 0.42 mm (pnoninferiority< 0.0001, psuperiority <0.0001)

– During clinical follow-up, no significant differences between stent groups

in the device-orientated composite end point (NES 2.9% vs. ZES 5.6%,

p= .45)


• Platinum chromium Element stent Platform

– Platinum chromium : twice as dense as iron or cobalt

chromium much greater radio-opacity.

increased radial strength

thinner stent struts reduce clinical and angiographic

restenosis

– strut thickness of 81 μm compared with 96 μm for the

TAXUS Liberté,

New metal stent plat-forms

Platinum chromium EES Element Stent

0.6

0.4

0.2

0.0

Performance Goal = 0.44 mm

0.170.25 mm*

(N=73)In-s

ten

t La

te L

oss

(Q

CA

) in

W

ork

hors

e L

esi

on

s (m

m)

Workhorse lesions: RVD ≥2.5–≤4.25 mm, lesion length ≤24 mm

* Mean ±SD; value of 0.17 with an upper confidence bound of 0.22 mm is significantly less (P<0.001) than performance goal based on historical TAXUS Express value (0.41 mm + delta [0.03 mm]); QCA=quantitative coronary angiography

PLATINUM QCA StudyPrespecified Efficacy Endpoint

9-Month In-Stent Late Loss – Workhorse Lesions

Presented by Ian Meredith, MBBS, PhD at TCT 2010.

P < 0.001

All death, MI, TVR 1.0% (1) 1.0% (1)

All death 0.0% (0) 0.0% (0)

Myocardial infarction 0.0% (0) 0.0% (0)

Q-wave 0.0% (0) 0.0% (0)

Non–Q-wave 0.0% (0) 0.0% (0)

Target vessel revascularization 1.0% (1) 1.0% (1)

Target lesion revascularization 1.0% (1) 1.0% (1)

Target lesion failure* 1.0% (1) 1.0% (1)

Stent thrombosis (ARC def/prob) 1.0% (1) 1.0% (1)

30 Days 9 Months

* Ischemia-driven TLR, or MI/cardiac death related to the target vessel

PLATINUM QCA Study Clinical Outcomes through 9 Months

One patient had a periprocedural ST with TLR & non-target lesion TVR

N=100

Presented by Ian Meredith, MBBS, PhD at TCT 2010.

• 1,532 pts in the randomized multicenter PLATINUM

(A Prospective, Randomized, Multicenter Trial to As-

sess an Everolimus-Eluting Coronary Stent System

[PROMUS Element] for the Treatment of up to Two De

Novo Coronary Artery Lesions) compared with the

cobalt chromium Promus EES

• Two parallel subtrials to evaluate the Promus Element

stent in small vessels and in long lesions.


• PERSEUS (A Prospective Evaluation in a Randomized Trial of the Safety and Efficacy of the Use of the TAXUS Element Paclitaxel-Eluting Coronary Stent System for the Treatment of De Novo Coronary Artery Le-

sions)– The noninferiority PERSEUS Workhorse trial– randomized, in a 3:1 ratio, 1,262 pts with lesions < 28 mm

vessels (2.75 to 4.0 mm) into the TAXUS Element (n 942) or the TAXUS Express PES (n 320)

– At 9 M angiographic follow-up, no significant difference in late loss between the Element and Express stents (Element 0.34 ± 0.55 mm vs. Express 0.26 ± 0.52 mm, p = 0.33).

– The rate of the primary end point of target lesion failure at 12 months : 5.6%, & 6.1% (p=0.78)

– no significant differences in the clinical end points of MACE, mortality, MI, and ST.

TAXUS Element stent


• PERSEUS (A Prospective Evaluation in a Randomized Trial of the Safety and Efficacy of the Use of the TAXUS Element Paclitaxel-Eluting Coronary Stent System for the Treatment of De Novo Coronary Artery Le-

sions)– The superiority PERSEUS Small Vessel trial, – compared the TAXUS Element stent to historical BMS – 349 pts with lesions 20 mm in length, vessels (2.25 to 2.75)– at 9 M f/up, a significantly lower primary end point of in-

stent late loss with the Element stent compared with the BMS stent (0.38 ± 0.51 mm vs. 0.80 ± 0.53 mm, p < 0.001)

– At 12 M f/up, the rates of target lesion failure and MACE were both significantly lower with the Element stent,

– ST were comparable between both stents.

TAXUS Element stent

• DES with Biodegradable Polymer

DES with Biodegradable Polymer

• 1. antirestenotic benefits of a standard DES,

2. once the polymer has biodegraded, they specula-

tively may offer the safety benefits of a BMS

• 1. optimal biocompatibility, composition, formulation,

and degradation time of the polymer.

2. pharmacokinetics of the antiproliferative agent re-

leased by the degradation of the polymer.

3. variation in polymer degradation time


• clinical advantage of stents with biodegradable poly-

mers is currently hypothetical.

• Clinical study limited by short-term follow-up, and

definitive data on the long-term benefits are lacking.

• Polymer breakdown can be associated with a signifi-

cant inflammatory reaction(acidic environment)

• persistent immune response to monomer breakdown

products


• Sirolimus based– Supralimus stent

– Excel stent

– Nevo stent

• Biolimus A9 based

– Biomatrix stent

– Nobori stent

– Axxess stent

– Xtent custom NX stent

• Myolimus based– Myolimus-eluting stent

• Palitaxel based

– Infinnium stent

– Jactax stent

– Synergy stent

Supralimus stent

• stainless steel SES with a biodegradable polymer mix

of poly-L-lactide (PLA), poly vinyl pyrrolidone, poly

lactide-co-caprolactone, and poly lactideco-glycolide

(PLGA).

• 1/2 of the sirolimus eluted by day 9, with elution being

complete within 48 days.

• the polymer, on the other hand, completely

biodegrades within 7 months.

Supralimus stent

• 100 pts SERIES I (Study of the Supralimus Sirolimus Eluting Stent in the Treatment

of Patients With Real World Coronary Artery Lesions) FIM study

– in-stent angiographic restenosis of 0.0%

– late loss of 0.09 ± 0.37 mm at 6 M.

– At 30 M, the rate of TVR 4%, with no definite ST

• eSERIES multicenter registry (6M f/up)

– over 1.100 pts, similar clinical effectiveness & safety at 6M

• Supralimus stent vs Infinnium PES vs BMS in the random-

ized, multicenter PAINT (Percutaneous Intervention With Biodegradable-

Polymer Based Paclitaxel- Eluting, Sirolimus-Eluting, or Bare Stents for the Treat-

ment Of De Novo Coronary Lesions) study of 274 low-risk patients.

Angiographic Findings at Baseline, Post-Procedure and 9 Months

PAINT

Clinical Outcomes After 12 Months of Follow-Up

No differences in the risk of death, infarction, or stent thrombosis among the study groups.

PAINT

SERIES III (ongoing)

• noninferiority trial

• randomize 400 pts to either Xience V or Supralimus

• the primary end point of 9-month in-stent late loss.

Nevo stent

• open-cell, cobalt chromium with a PLGA biodegrad-

able polymer and sirolimus elution

• polymer and sirolimus are contained within

reservoirs :

– eliminates need for a surface polymer coating, thereby re-

ducing tissue–polymer contact by over 75%

– cf. Costar stent

Nevo stent design

NEVO stent

• NEVO-RES I (NEVO RES-ELUTION) study

– randomized, multicenter, noninferiority study

– NEVO vs TAXUS Liberté PES stent in 394 patients with sin-gle de novo coronary artery lesions.

– At 6M angiographic f/up, the primary end point of in-stent late lumen loss significantly lower in NEVO stent (0.13 mm vs. 0.36 mm, p<0.0001)

– a superiority preserved irrespective of DM, lesion length, or vessel diameter

– Clinical end points at both 6 & 12 M numerically lower in the NEVO-treated group,

– The rate of ST was 0.0% (NEVO) and 1.1% (p = 0.24)

• NEVO II and NEVO III in future trials

NEVO-RES I (NEVO RES-ELUTION) study

Biolimus A9 based stent

• highly lipophilic sirolimus analogue

• combined with an abluminal PLA biodegradable

polymer on a number of different stent platforms.

• polymer biodegrades within 6 to 9 M

• abluminal location of polymer

– more targeted tissue release

– reduced systemic exposure.

• encouraging clinical results

The elution pattern of Biolimus A9 & corre-sponding biodegradation pattern of the poly-lactic acid (PLA) polymer.

Biomatrix stent

Biomatrix stent

• all-comers LEADERS (Limus Eluted from A Durable versus

Erodable Stent coating) trial

– Biomatrix vs Cypher in 1.707 pts in randomization

– noninferior for MACE, a composite of cardiac death, MI, and

ischemia driven TVR at 12 M f/up (Biomatrix 10.6% vs.

Cypher 12.0%, p = 0.37)

– preservation of this noninferiority at 2-year follow-up

– stent’s PLA polymer completely biodegraded by 9 M

– fewer very late ST events (1 year) with the Biomatrix stent

(0.2% vs. 0.5%)

LEADERS: Primary EndpointCardiac Death, MI, or TVR @ 9 months

00

55

1010

1515

850850 791791 786786 784784 781781 777777 771771 758758 751751 746746857857 806806 798798 796796 792792 784784 779779 777777 771771 761761

No. at riskNo. at risk

00 11 22 33 44 55 66 77 88 99Months of Follow-upMonths of Follow-up

SESSESBESBES

Cum

ula

tive Inci

dence

(%

)C

um

ula

tive Inci

dence

(%

)

Sirolimus Stent 10.5%

Biolimus Stent 9.2%

Risk Difference -1.3%, Upper Limit 95% CI 1.1%Pnon-inferiority = 0.003

Rate Ratio = 0.88, 95% CI 0.64 - 1.19

Biolimus A9 based stent

• OCT substudy

– higher rate of near

complete (95%) strut

coverage with the

Biomatrix stent (vs

Cypher SES at 9M

follow-up (89.3% vs.

63.3%, p 0.03)

Nobori stent

Nobori stent

• NOBORI CORE study

– late loss at 9 M f/up in 99 patients randomized to Nobori vs Cypher SES

: 0.10 mm vs 0.12 mm, (p= 0.66)

– significantly better recovery of endothelial function with the Nobori

• Nobori I study

– Randomized 243 patients to Nobori stent (n=153) vs TAXUS stent (n= 90)

– at 9 M, noninferiority, and subsequent superiority, of the Nobori stent with

respect to late loss (0.11 mm vs. 0.32 mm, pnoninferiority <0.001, psuperiority <

0.001)

– ST at 9M lower with the Nobori stent (0.0% vs. 2.2%)

NOBORI CORE

Nobori stent

• NOBORI CORE study

– late loss at 9 M f/up in 99 patients randomized to Nobori vs Cypher SES

: 0.10 mm vs 0.12 mm, (p= 0.66)

– significantly better recovery of endothelial function with the Nobori

• Nobori I study

– Randomized 243 patients to Nobori stent (n=153) vs TAXUS stent (n= 90)

– at 9 M, noninferiority, and subsequent superiority, of the Nobori stent with

respect to late loss (0.11 mm vs. 0.32 mm, pnoninferiority <0.001, psuperiority <

0.001)

– ST at 9M lower with the Nobori stent (0.0% vs. 2.2%)

• Overall, the evaluation of the Nobori stent has so far been

performed in over 3,000 patients

– no episodes of very late ST have been reported.

• Randomized comparisons in “real-life” populations with

the Xience V in the COMPARE 2 (n 2,700) and BASKET

PROVE 2 (n 2,400) studies; and the Cypher Select in

SORT-OUT IV study (n 2,400)

JACTAX Liberte PES stent

• stainless steel PES• Novel ultrathin abluminal PLA polymer : Juxtaposed Abluminal

Coating technology (JAC)• This polymer has a microdrop structure– 16-mm JACTAX stent : 2,700 microdots, – each containing 3.4 ng of polymer (total 9.2 ug)

• The polymer only applied to the outer surface of the stent, : min-imal polymer, with little strut-to-strut or balloon-to-strut polymer interaction

• The thickness of the polymer (<1 um) 18 x less than TAXUS Lib-erté stent, (polymer mass is 100 x less)

• Paclitaxel combined with the polymer in a 1:1 ratio and subse-quently released in a controlled manner over 90 days, whereas the polymer is fully resorbed within 6 to 9 M

JACTAX Liberte PES stent

• coating of LD vs HD paclitaxel

– HD preparation still only contains 1/10 of dose of paclitaxel as

found on the TAXUS Liberté stent.

– Preliminary analysis of OCT data from the OCTDESI study

• suggests that the use of a lower dose of paclitaxel has no significant ad-

verse effect on the stent’s overall performance

• OCTDESI (Optical Coherence Tomography Drug Eluting Stent Investigation)

– Randomized 60 patients to treatment with the JACTAX LD, JACTAX HD,

and TAXUS Liberté stents,

– Comparative proportion of uncovered stent struts, and neointimal volume

among all 3 stents at 6 M f/up

• JACTAX (Juxtaposed Abluminal Coating TAXUS) HD FIM

– 103 pts who received a JACTAX HD stent

– angiographic results compared with 217 historical matched

controls treated with the TAXUS Liberté stent from the AT-

LAS study

– lower rates of in-stent late loss (0.33 mm in JACTAX HD vs.

0.39 mm, p = 0.36) & binary restenosis (5.2% vs. 9.2%, p=

0.22) at 9 M f/up

– the rate of the primary end point of MACE : 7.8% (meeting

the criteria for noninferiority);

– there were no deaths, Q-wave MIs, or ST during follow-up

• JACTAX LD DES trial coming

JACTAX HD Results vs. ATLAS Matched (9 months)

TaxusLiberté(n=223)

TaxusLiberté(n=223)

LabcoatLiberté(n=96)

LabcoatLiberté(n=96)

Late

Loss

(m

m)

In-Stent In-Segment

p=0.23 p=0.17

• Nonpolymeric DES

Nonpolymeric DES

• avoiding the adverse effects of a polymer’s presence

long term

• Improved healing

• improvement to the integrity of the stent’s surface

• possibility of a shorter duration of DAPT

Nonpolymeric DES

• How to elute drug in controlled manner ?

– Dissolving the antiproliferative agent into a nonpolymeric

biodegradable carrier on the stent’s surface.

– Impregnating the antiproliferative agent in pure form onto

the porous surface of the stent.

– Attaching the antiproliferative agent directly to the stent sur-

face using either covalent bonding or crystallization/ chemi-

cal precipitation

Nonpolymeric DES

• YUKON DES

• BioFreedom

• VESTAsyn sirolimus-eluting stent

• Amazonia Pax

Translumina Porous Surface Stent

PureSirolimus

• Selectively micro-structured sur-face holds drug in abluminal sur-face structures

BioMatrix Freedom Stent

Micro-structured Surface

Abluminal coating – 5µ thickness applied on crimped stent.

Consistent coating ensuring 98% of the drug delivered to the site.

Polymer free Paclitaxel.

2.5µg/mm² dose.

Boost-release (60% in 2 days)

Profile release established in 30 days (98% of

the drug)

Back to regular Chromium Cobalt after 45 days.

Abluminal coating – 5µ thickness applied on crimped stent.

Consistent coating ensuring 98% of the drug delivered to the site.

Polymer free Paclitaxel.

2.5µg/mm² dose.

Boost-release (60% in 2 days)

Profile release established in 30 days (98% of

the drug)

Back to regular Chromium Cobalt after 45 days.

Polymer Free PaclitaxelPolymer Free Paclitaxel

Nonpolymeric DES

Nonpolymeric DES

ISAR–TEST-3

• Long-term data from angiographic obser-

vational

study of 1,331 pts

• significantly lower change in late loss be-

tween

6 to 8 months and 2 years for the YUKON

stent

vs SES and PES

• YUKON 0.01 ± 0.42 mm

• SES 0.17 ± 0.50 mm

PES 0.13 ± 0.50 mm, p<0.001

Not prone to late catch up phenomenon

• Biodegradable Stents

Biodegradable Stents

• potential reductions in adverse events (ST)

– no triggers for ST, such as nonendothelialized stent struts, or

drug polymers are present long term

• reduce the requirements for long-term DAPT, reducing

the risk of associated bleeding complications.

• Physiologically, facilitate the return of vessel vasomo-

tion, adaptive shear stress, late luminal enlargement,

and late expansive remodeling.


• improvement in future treatment options (PCI or sur-gical revascularization for areas of previous stenting without restriction)

• negation of the other problems associated with use of permanent metallic stents – covering of side branches

– overhang at ostial lesions

– “blooming effect” seen with noninvasive imaging techniques

• eliminate the concerns that a minority of patients have at the thought of having “an implant in their bodies for the rest of their lives


• Polymer or metal alloy

: Poly-L-lactic acid

: 12 to 18M


• 3 major hurdles to using polymer as backbone of stent

– lack of radio-opacity, which necessitates radio-opaque stent

markers

– the reduced radial force as compared with stainless steel, ne-

cessitating thicker stent struts

– Reduced ability of the stents to be deformed.

• At present, no BDS has either the C.E. mark or U.S.

FDA approval


• PLLA stents

– IGAKI-TAMAI stent

– Abbott vascular bioresorbable vascular scaffold (BVS)

– REVA stent : POLY (IODINATED DESAMINOTYROSYLTYROSINE ETHYL ES-

TER) CARBONATE STENT

– IDEAL POLY(ANHYDRIDE ESTER) SALICYLIC ACID

STENT

• Biodegradable metallic stent technology

– Absorbable metallic stent (AMS-1 BDS)

Igaki-Tamai stent

►Polymer: PLLA

►Metabolizes to: CO2 and Water

►Not a DES

►Design: Zig-Zag hoops with straight connector

►Stent measurements Strut thickness 170 microns, S/A 24%, pro-file?

►Deployment: Self expanding, sheathed

Balloon inflation with heated contrast

►In the FIM trial of 50 pts followed for 4 years there were no safety concerns- similar to BMS

►No coronary implants since FIM Tamai Circulation 2000:102:399 Tamai CCT 04

►Material: Poymer is PLLA for stent backbone and PDLLA for the coating

►Metabolizes to: CO2 and Water►►Radio-opacity: Platinum markers at each end►Deployment: Balloon expandable

►Stent measurements 150 microns + 6 microns coating S/A 25%, profile 1.4mm

►Radial strength Similar to MultiLink at implantation

►Drug Everolimus-eluting

Ormiston, ACC 08

BVS (Ab-bott)

REVA Bioabsorb-able Stent (REVA Medical)

REVA Bioabsorb-able Stent (REVA Medical)►Polymer: Tyrosine-derived Polycarbonate

►Breakdown: amino acids, ethanol, and CO2

►Drug-elution Nil in FIM

►Deployment: Balloon expandable- slide and lock design (ratchet)

►Stent properties Strut thickness 200 micron, crossing profile 1.7mm, S/A 55%

►Radio-opacity: Impregnated with iodine

►RESORB FIM 27 patients- “Interim analysis showed unfavourable results between 4 and 6 months” Grube, TCT 08,

Bioabsorbable Mg

Alloy Stent (Bio-tronik)►Material: Magnesium Alloy

►Not DES

►Design: Circumferential in-phase sinusoidal hoops and straight bridges

►Deployment; Balloon expandable

►Strut thickness: 165 microns

►Crossing profile <1.2mm

►Radioluceny/opacity: not visible on fluroscopy

Erbel, Lancet 2007;369: 1869

PROGRESS AMS FIM Trial with magnesium alloy stent implantation in 63 patients

High restenosis rate (47.5%) and TLR (45%) because

1.Stent absorbed too quickly to with-stand negative remodelling forces

2.No antiproliferative drug

Erbel, Lancet 2007;369: 1869

Bioabsorbable Mg

Alloy Stent (Bio-tronik)

• Stents with Novel Coatings

Stents with Novel Coatings

• Catania stent

• Titan-2 stent

• Genous Bio-engineered R-stent

Catania stent

• cobalt chromium, modified open-cell stent

• modified by a 40-nm-thick coating of the NanoThin

Polyzene-F polymer (standard DES polymer thick-

nesses are 5.3–16 μm).

– Polyzene F is a biocompatible, biostatic, proprietary formu-

lation of poly[bis(trifluoroethoxy)-phosphazene]: anti-in-

flammatory, bacteria resistant, & pro-healing qualities

– very low surface thrombogenicity : potentially reduce ST

Catania stent

• FIM ATLANTA (Assessment of The LAtest Non-Thrombogenic Angio-

plasty stent) study in 55 pts.– 6M late lumen loss of 0.6 mm

– 12M f/up, no deaths or MI, and a clinically driven TLR rate of 3.6%

– No ST despite DAPT given for only 30 days.

– OCT study in 15 patients : 99.5% of struts were fully covered at 6 M

• ATLANTA-II prospective registry– 300 patients (14% STEMI)

– At 1-year, the cumulative rate of MACE was 8.8% individual rates of

cardiac death, MI, & TLR of 2.5%, 0.7%, and 6.5%

– DAPT given for only 30 days

– rate of ST was 0.7% due to 2 cases of subacute ST

Genous Bio-engineered R stent

• bare-metal stainless steel stent

• immobile CD34 antibodies on its luminal surface

: endothelial progenitor cells (EPCs) capture stent

: rapidly formed, functional endothelial covering of the stent’s

struts to reduce ST and restenosis

• CD34 markers : nonspecific,– shared by other hematopoietic stem cells

– EPC capture stent to sequester other bone marrow cell lines

such as smooth muscle progenitor cells neointimal prolif-

eration



• low rates of ST despite only 1 month of DAPT

• however, late loss at 6 M f/up above 0.6 mm

• TRIAS (TRI-stent Adjudication Study) HR study

– only randomized trial published so far

– late loss as high as 1.14 ± 0.64 mm

– overall higher target vessel failure with the Genous stent compared with

the TAXUS PES

• preliminary data at 2-year f/up

– lower absolute increase in TLR between 1 and 2 years in those

treated with EPC stent compared to PES

– regression of late loss with the EPC stent (HEALING II) Ad-

ditional promising data

• e-HEALING registry

– 5000 pts

– rates of MACE, MI, and ST at 1-year f/up of 7.7%, 1.7%, and

1.0%, respectively

Combo stent

• DES (abluminal low-dose sirolimus and a biodegradable poly-

mer ) + EPC capture technology to enhance vessel healing

• histology and OCT at 28-day follow-up in the porcine model

– compared with the standard SES and Genous EPC stent

– Promotes endothelialization

– reducing neointimal formation and inflammation

• REMEDEE (Randomized Evaluation of an Abluminal sirolimus coated

Bio-Engineered Stent) FIM study

– Randomize 180 patients to either the Combo Stent or the TAXUS Lib-

erté PES with a primary end point of late loss at 9M f/up

• Dedicated Bifurcation Stents

conventional stenting techniques for bifurcation lesions

• the inability to completely scaffold the side-branch ostium

• distortion of the main-branch stent following side-branch dila-

tion

• the difficulty of maintaining access to the side branch through-

out the procedure

• Failure to wire the side branch through the main-branch stent

• side-branch jailing

Dedicated Bifurcation stents

• device success high,

• rates of additional stenting of up to 40

• the early devices were bare metal

– subsequent rates of restenosis were similar to those ob-

served with PCI of bifurcation lesions using BMS

– high rates of MACE and TLR

• Second generation devices (DES)

– The evaluation of these newer devices is ongoing

– randomized trials against conventional DES are still lacking

• Summary and Conclusions

• no single stent design and polymer type will be suitable for all patients and lesion types. • more individualized choice of stent, taking into account patient characteristics such as the ability to take long- term DAPT, and lesion characteristics such as presence or not of a bifurcation lesion will be important factors influencing stent selection.• Reassuringly, the new stent technology appears to allow interventional cardiologists to make these choices, and there is great anticipation that this will result in improved long-term clinical efficacy and safety.

Documents

New Drug-Eluting Stents Soo-Joong Kim M.D., PhD. Department of Cardiology, Internal Medicine, Kyung Hee University Medical Center