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DES: NEW GENERATION OF STENTS and NEW 

ERA OF AWARENESS 

Patrick W. Serruys MD PhD FACC FESC 

Thoraxcenter 

Erasmus Medical Center 

Rotterdam, The Netherlands 

No Disclosure 

CIT 2007 BEJING March 30 15.00-15.20 

15.20

ESC firestorm: Issue #1 death and MI 

“Our Black Tuesday”

1 st endpoint: Death, MI 

2 nd endpoint: stent thrombosis 

1 st endpoint: stent thrombosis 

2 nd endpoint: Death, MI 

6-12 mts 3 years 

RT 

“Revolution” 

“Trias HR” 

“Protect” 

Costar 

Genous 

Endeavor 

Durable polymer 

Taxus 

Cypher 

3 years 3 years 

RT 

ASA/Prasugrel 

ASA/Clopidogrel 

Late stent thrombosis 

Going to Pharma 

“Fight” between 1 st gen DES 

“Fight” between DES and non-DES 

New development 

New coating (absorbable coating, no coating) 

Absorbable metallic or polymeric platform 

New Biological target (thrombosis 

, inflammation) 

New drug (no cytostatic or cytotoxic) 

New technique of elution (dual elution) 

Pro Healing approach (EPC capture) 

Pro Healing approach +Sirolimus+ 

or Paclitaxel






RT 



“Protect” 

Costar 

Genous 

Endeavor 


Taxus 

Cypher 


RT 

ASA/Prasugrel 















or Paclitaxel






RT 



“Protect” 

Costar 

Genous 

Endeavor 


Taxus 

Cypher 


RT 

ASA/Prasugrel 















or Paclitaxel






RT 



“Protect” 

Costar 

Genous 

Endeavor 


Taxus 

Cypher 


RT 

ASA/Prasugrel 














Pro Healing approach +Sirolimus or Paclitaxel

Survey of the next generation of 

drug-eluting stents: meaningful 

advances or more of the same 

1 New coating (absorbable coating, no coating) 

2 Absorbable metallic or polymeric platform 

3 New Biological target (thrombosis , inflammation) 

4 New drug (less cytostatic or cytotoxic) 

5 New technique of elution (reservoir, dual elution) 

6 Pro Healing approach (EPC capture) 

7 Pro Healing approach +Sirolimus+ 

or Paclitaxel





Problems with the polymer 

•Inflammatory response 

•Increased thrombogenicity 

•Non-homogenous drug distribution 

•Flaking, peeling, webbing, bonding

NEW COATING, NO COATING, ABSORABLE COATING 

From durable to absorbable polymer ,to EPC capture , 

to bioabsorbable platform 

Manufacturer Name Drug Stent material Polymer Status 

Cordis Cypher Sirolimus Stainless steel Durable CE Mark 

Boston Scientific Taxus Paclitaxel Stainless steel Durable CE Mark 

Medtronic Endeavor Zotarolimus Cobalt chromium Durable CE Mark 

Medtronic Resolute Zotarolimus Cobalt chromium Durable CE Filed 

Abbott ZoMaxx Zotarolimus Tantalum/stainless steel Durable Not Filed 

Abbott Xience V Everolimus Cobalt chromium Durable CE Mark 

Braun Coroflex Paclitaxel Cobalt chromium Durable CE Mark 

Biosensors BioMatrix Biolimus-A9 Stainless steel Bioabsorbable CE Filed 

Conor CoStar Paclitaxel Cobalt chromium Bioabsorbable CE Mark 

Sahajanand Supralimus Sirolimus Stainless steel Bioabsorbable CE Mark 

Sahajanand Infinnium Paclitaxel Stainless steel Bioabsorbable CE Mark 

Terumo Nobori Biolimus-A9 Stainless steel Bioabsorbable trial 

Kaneka Mahoroba Tacrolimus Cobalt chromium Biodegradable FIM 

Biotronick Progenic Pimecrolimus Cobalt chromium Bioabsorbable FIM 

Sorin Janus Tacrolimus Stainless steel None CE Mark 

Sorin Carbostent Tacrolimus Cobalt chromium Excipients FIM

NEW COATING, NO COATING, ABSORABLE COATING 

From durable to absorbable polymer ,to EPC capture , 

to bioabsorbable platform 

Manufacturer Name Drug Stent material Polymer Status 

Orbus Neich Genous EPC capture Stainless steel Durable CE Mark 

Orbus Neich Genous EPC capture Cobalt chromium Durable R & D 

Orbus Neich Fully absorbable combination drug-eluting and EPC capturing R & D 

Orbus Neich Combo EPC capture 

+ sirolimus 

or paclitaxel 

Biotronik AMS2 New design and new alloy 

Biotronik Dreams AMS2 with drug containing matrix 

Stainless steel Durable R & D 

Biotronik AMS Absorbable metal (Mg) trial 

Abbott BVS Everolimus Biodegradable trial 

Abbott BVS 1.1 Everolimus Biodegradable Trial 

MIVT Smart Midastaurin 

or sirolimus 

or zoledronic 

acid 

Stainless steel Hap R & D 

Sahajanand Isoflavone Cobalt chromium Bioabsorbable R & D

# 1 The # New “high durable tech “ of polymer the new from generation Medtronic of polymer 

• C10 Polymer 

Based primarily on hydrophobic butyl 

methacrylate to provide adequate 

hydrophobicity for zotarolimus 

CH 2 

C 

CH 2 CH 

CH 3 

a 

C O 

O 

O 

C10 

C 

O 

b 

C 4 H 9 

CH 3 

• C19 polymer 

Manufactured from a mixture of 

hydrophobic hexyl methacrylate and 

hydrophilic vinyl pyrrolidinone and vinyl 

acetate monomers to provide enhanced 

biocompatibility 

CH 2 

C19 

CH 3 

C 

CH 2 CH 

CH 2 CH 

x y z 

C O 

N 

O 

O 

O 

C O 

C 6 H 13 

CH 3 

• Polyvinyl pyrrolidinone (PVP) 

Hydrophilic polymer increases initial 

drug burst and enhances 

biocompatibility 

PVP 

CH 2 CH 

N 

a 

O 

The BioLinx Polymer System 

Caution: ENDEAVOR RESOLUTE is an investigational device with an investigational drug, not approved for sale or commercial use.

ENDEAVOR RESOLUTE Polymer System 

Hydrophilic 

zotarolimus 

Hydrophobic 


This new coating decreases the usual Monocyte Adhesion 

to the classic hydrophobic DES Polymers 

120 

100 

Relative % Adhesion 

80 

60 

40 

20 

0 

Negative 

Control 

Positive 

Control 

Resolute PBMA S-IB-S 

BioLinx 

Activated monocytes (U937,LPS+PMA) 

PBMA: Polybutyl methacrylate [Cypher cap coat] 

SIBS: Styrene-Isobutylene-Styrene Triblock Copolymer [Taxus] 


Counteract the Up-Regulation of 

Prothrombotic Genes by PBMA and SIBS 

BioLinx PBMA 

SIBS 

BioLinx 

PBMA 

SIBS 

Tissue Factor -Tissue factor is a potent 

initiator of the coagulation cascade shown 

to be important in the pathogenesis of 

thrombosis and restenosis after balloon 

angioplasty 4 . 

PAI-1 -Plasminogen activator inhibitor-1, 

plays a key role in fibrin homeostasis and 

is a central component in the pathogenesis 

of vascular diseases, such as 

atherosclerosis and restenosis 5 

4. R. Shebuski et al, J Pharmacol Exp Ther. 2002. 300: 729 

5. S. Nicholl et al, Curr Vasc Pharmacol. 2006. 4:101

Enhances the Expression of eNOS mRNA 

Endeavor implanted vessel expressed eNOS mRNA 

significantly higher than Both Cypher and Taxus 

28 day 

28 day 

1.2 

1 

0.8 

0.6 

0.4 

0.2 

0 

3.5 

3 

2.5 

2 

1.5 

1 

0.5 

0 

Stented region 

* * 

Endeavor Cypher Taxus Driver 

Proximal region 

* 

Endeavor Cypher Taxus Driver 

Cypher 

Immunohistochemistry 

Resolute 

Endeavor 

*P

Cypher and Taxus constrict in response to acetylcholine (ACH) 

suggesting EC dysfunction 

Endeavor show normal vasodilation in response to ACH suggesting 

normal EC function 

Cypher (n=9) 

Taxus (n=8) 

4.50 

4.50 

4.00 

4.00 

3.50 

3.50 

3.00 

3.00 

2.50 

2.50 

2.00 

2.00 

1.50 

1 2 

1.50 

1 2 

Baseline Ach (10 -6M ) 

Baseline Ach (10 -6M ) 

Endeavor (n=15) 

4.50 

4.00 

3.50 

3.00 

2.50 

2.00 

1.50 

1 2 

Baseline Ach (10 -6M )

# Porous and micro-porous 

Porous Stent Surface and Coating Device 

cartridge 

positionable ring 

with several jet units 

stent 

drug 

syringe 

Porous, PEARL Surface 

Rapamycin Coated Yukon

Hydroxyapatite 

Coating 


Closely resembling biological 

apatite (bone !) 

Biocompatible, bioactive and 

bioresorbable 

Substrate 

*Electro-Chemical Deposition 

Rajtar A, A et al. EuroInterv 2006; 2: 113-5


Nanocarbon coating: 

Adjustment of pore size 

Carbon-carbon composite 

Porous glassy/ pyrolytic carbon 

Pore size from 20nM to 2µM2 

Porosity from 50-70% 

Layer thickness 200 nM to 5 µM 

Extraordinary elasticity

EXPANDING THE SCAFFOLD AND 

THE INTERACTIVE SURFACE 

Composite 

R stent











or Paclitaxel

#2 BIOABSORBABLE METAL STENT in Magnesium 

Light Microscopy 

Scanning Electron Microscopy 

Continuous immersion test of stents 

in 0.9% NaCl; 37°C; pH 7.0

#2 BIOABSORBABLE METAL STENT in Magnesium 

PROGRESS-AMS trial 

angiographic result 

MLD pre 1.05 ± 0.38 mm 

MLD stent 2.47 ± 0.37 mm 

MLD follow-up 

1.38 ± 0.51 mm 

Acute Gain 1.41 ± 0.46 mm 

Late Loss 1.07 ± 0.50 mm 

Restenosis : 51 %

#2 BIOABSORBABLE METAL STENT WITH DRUG 

One technical solution to convert this non-eluting absorbable 

metallic stent in to an eluting stent was to ‘Conorize’ this structure 

“Conorized” AMS 

Elution of Pimecrolimus from 

CoCr Conor vs. ‘Conorized’ AMS

#2 BIOABSORBABLE METAL STENT WITH DRUG 

New alloys and new design

ML VISION ® SDS 

Polymeric Eluting (PLA) 

Everolimus 

PLA 

H 2 O 

↓ Molecular Weight 

Hydrolysis 

Lactic Acid 

Mass Loss 

Mass Transport 

Krebs 

Cycle 

CO 2 + H 2 O

Late Loss 

100 

80 

60 

40 

20 

EES ** : 0.10 ± 0.23mm (N=22) 

BVS: 0.44 ± 0.35mm (N=26) 

BMS*: 0.85 ± 0.36mm (N=27) 

0 

-0.4 0 0.4 0.8 1.2 1.6 2 

* BMS loss from SPIRIT FIRST ( n=27 ) 

Unmatched views 

** EES loss of pts with 3.0 x 18mm for single lesion 

from SPIRIT FIRST and II ( n=22 ) 

ACC 2007

What is Contributing to Late Loss 

SPIRIT-First 

ML Vision Stent 

SPIRIT-First 

Xience V Stent 

ABSORB 

BVS Stent 

Late Loss = 0.87mm Late Loss = 0.10mm Late Loss = 0.44mm 

Δ Vessel Area = -1.9% 

Δ Stent Area = -2.0% 

Δ Lumen Area = -29.4% 

NIH Area (mm 2 ) = 1.98 

% VO = 28.1% 

Δ Vessel Area = +1.2% 



NIH Area (mm 2 ) = 0.50 

% VO = 8.0% 

Δ Vessel Area = -0.4% 



NIH Area (mm 2 ) = 0.30 

% VO = 5.5% 

ACC 2007

ACC 2007 

Clinical Results 

Hierarchical 

30 Days 

30 Patients 

6 Months 

30 Patients 

Cardiac Death (%) 0.0% (0) 0.0% (0) 

MI (%) 0.0% (0) 3.3% (1)* 

Q-Wave MI 0.0% (0) 0.0% (0) 

Non Q-Wave Q 

MI 0.0% (0) 3.3% (1)* 

Ischemia Driven TLR (%) 0.0% (0) 0.0% (0) 

by PCI 0.0% (0) 0.0% (0) 

Ischemia Driven MACE (%) 0.0% (0) 3.3% (1) * 

This patient also underwent a TLR , not qualified as ID –TLR , since the DS was 42 %











or Paclitaxel

The LIMUS Family of Drugs 

In-Stent Late Loss (mm) 

….more of the same 

4 months 

6-8 months 12 

months 

Sirolimus 0.09 REALITY* 

Sirolimus/heparin 0.27 

Everolimus 0.10 - 0.11-0.14 

0.14 0.24 

Biolimus-A9 

0.17- 0.15 

Zotarolimus 0.12 

Tacrolimus 0.67 

Harmony* 

SPIRIT-I/ / II/III* 

STEALTH / NOBORI 

RESOLUTE 

JUPITER-II II * 

*QCA analysis (1st or 2nd reading) by Cardialysis in Rotterdam

The LIMUS Family of Drugs – more of the same 

NO 

Courtesy of R Virmani



The LIMUS Family of Drugs – more of the same



NEW DRUGS-BiolimusA9 

incorporated with new stent technology (DEVAX,XStent) 


4 months 

6-8 months 12 

months 

Sirolimus 0.09 REALITY* 


Everolimus 0.10 - 0.11 0.24 

Biolimus-A9 

0.17- 0.15 

Zotarolimus 0.12 


Harmony* 

SPIRIT-I/ / II* 

STEALTH / NOBORI 

RESOLUTE 

JUPITER-II II * 


NEW DRUGS-BiolimusA9 

incorporated with the Xtent technology 

Delivery 

System 

Sheath protected 

Adjustable balloon length 

Multiple deployments 

Stent 

Interdigitated 

6mmCoCrsegments 

Lengths: 60mm & 36mm 

Diameters: 2.5, 3.0 & 3.5mm 

Drug Coating 

Biolimus A9 ® 

Biodegradable Drug 

Carrier (PLA)

NEW BIOLOGICAL TARGET NEW DRUGS-BiolimusA9 

incorporated with the Xtent technology











or Paclitaxel

The limus drugs: mechanisms of action 

#3 NEW BIOLOGICAL TARGET- NEW DRUG : 

TACROLIMUS,PIMECROLIMUS,ISOFLAVONE 

PDGF 

FGF 

IL-2 

Tacrolimus 

Pimecrolimus 

cytosol 

Protein 

Kinases 

mTOR 

FKBP 506 

Protein Synthesis 

Cdk2, elF-4F, 70-kD S6 kinase 

Cell Growth 

G0 

G1 

Downregulation 

p27 

S 

Calcineurin 

Tacrolimus 

Pimecrolimus 

Blocks T- 

cell 

activation 

Tacrolimus 

NFAT 

Cytokines 

Pimecrolimus 

M 

G2 

NFAT

NEW BIOLOGICAL TARGET NEW DRUGS-TACROLIMUS 

Superiority of Tacrolimus 

Sirolimus, but not Tacrolimus, inhibits 

endothelial cells proliferation 

Steffel, J. et al. Circulation 2005;112:2002-2011


Sustained Release of Tacrolimus (KANEKA) 

Concentration in the vessel wall 

Cumulative release

# 4 NEW BIOLOGICAL TARGET- NEW DRUG : 

TACROLIMUS,PIMECROLIMUS 

Immunocytochemistry of the endothelial layer shows a fully functional endothelium in the high dose 

group, as illustrated by the presence of E-NOS expression and the absence of vWF expression (the 

brown colored product on the endothelium (arrow)) 

neointimal area [mm2] 

5.00 

4.50 

4.00 

3.50 

3.00 

2.50 

2.00 

1.50 

1.00 

0.50 

0.00 

1.71 

2.43 

after 3 months 

0.70 

0.98 

bare polymer DL DH

MAHOROB 

A 

“MAHOROBA” 

The great place 

Tacrolimus 

Biodegradable 

Polymer PLGA 

kaneka original 

Stent Platform 

(CoCr alloy) 

FORTIS-based 

Stent Delivery 

System

CARBOSTENT SRT: The Platform Stent 

Co Cr structure derived by CHRONO, the new Non DES of Sorin 

• Thinner struts 

• Larger available 

volume for the drug 

• Wider total exposed 

area of the reservoirs

CARBOSTENT SRT: the excipients 

ASCORBYL PALMITATE: 

• Ester of two physiological molecules: vitamin C and the 

common fatty acid palmitic acid. 

• The ester is hydrolyzed and the two compounds enter normal 

physiological cycles. 

•POLY VINYL PYRROLIDONE: 

•Biosoluble hydrophylic component, known since 1939. 

•Mw = 7-11.000 (Mw inferior to 25K pass the glomerulus 

filter); T1/2 ≈ 72h











or Paclitaxel

#5 DUAL ELUTION HEPARIN AND SIROLIMUS 

Thrombosis 

Smooth Muscle Cell 

Migration/Proliferation 

(% Response) 

Inflammation 

Extracellular Matrix 

Production 


Reabsorption 

3 

14 90 

440 1000 

The combination of Heparin and Sirolimus prevents vascular 

smooth muscle cell proliferation and in-stent thrombosis 

simultaneously.

# ABSORBABLE COATING in Heparinized PLA polymer 

Heparin is coupled with Poly L-Lactide to create a heparinized 

polymer which will serve as a reservoir for another drug 

H 

O 

O 

O 

O 

OH 

* O 

COO- 

O 

OH 

O 

OSO 3 

- 

CH 2 

OSO 3 

- 

O 

OH 

O 

NHSO 3 

- 

* 

Monomer of PLA 

Heparin molecule 

O 

O 

O 

O 

O 

O 

DCC / DMAP 

OSO 3 

- 

OH 

O 

CO 

O 

CO 

O 

HO 

OSO 3 

- 

Formamide / DMF 

O 

OH 

COO- 

COO- 

O 

HO 

NHSO 3 

- 

O 

O 

NHSO 3 

- 

O 

O 

PLA conjugate Heparin


Elution Profile of Heparin – Sirolimus DES 

16mm Stent 

Cumulative Drug Release Profile for 

Heparin-Sirolimus eluting stent 

Cumulative Heparin Release 

Cumulative Sirolimus Release 

Amount Drug Released (mcg) 

120 

110 

100 

90 

80 

70 

60 

50 

40 

30 

20 

10 

0 

1 4 7 10 13 16 19 22 25 28 31 34 37 40 43 46 49 52 55 58 61 64 

Time (days) 

Both therapeutic agents elutes simultaneously. Heparin will 

give effect almost for 50 days and Sirolimus for 60 days. 

Sahajanand Medical Technologies Pvt. Ltd


Surface characterization by Scanning Electron Microscopy (SEM) 

of Heparin-Sirolimus stent in normal, crimped and expanded 

conditions. 

Sahajanand Medical Technologies Pvt. Ltd



4 months 

6-8 months 12 

months 

Sirolimus 0.09 REALITY * 


Everolimus 0.10 - 0.11 0.24 

Biolimus-A9 

0.17 

- 0.15 

Zotarolimus 0.33 0.61 


Harmony* 

SPIRIT-I* 

I*/ / II* 

STEALTH*NOBORI* 

ENDEAVOR-I 

JUPITER-II* 

II* 


# 5 NEW BIOLOGICAL TARGET- NEW DRUG : 

TACROLIMUS,PIMECROLIMUS 

Inflammation 

Smooth Muscle Cell 

Migration/Proliferation 

(% Response) 

Thrombosis 


Production 


Reabsorption 

3 

14 90 

440 1000

#5 DUAL ELUTION PACLITAXEL AND PIMECROLIMUS 

Conor Dual Drug Stent 

Paclitaxel 

Pimecrolimus


Pimecrolimus reduce peristrut inflammation 

BARE 

PIMECROLIMUS 

Pimecrolimus 

Dual elution paclitaxel/pimecrolimus 

pimecrolimus reduce neointima


QCA: Late Loss at 28 Days 

1.20 

1.00 

P











or Paclitaxel

#6 ENDOTHELIAL PROGENITOR CELL CAPTURE 

EPC Capture Coating Technology 

Intermediate Layer 

Stent Adhering 

Bottom Layer 

Human progenitor 

cell with CD34 Cell 

Surface Antigen 

Stent Surface 

Captured EPC on 

Surface using bond 

Antibodies 

CD34 Antibody Layer


Bare metal 

48 hr explant Balloon injured porcine arteries 

coated stents with monoclonal antibody against CD34 

capturing Endothelial Progenitor Cell to accelerate the 

Healing Process are in clinical trial !


Correlation in-stent late luminal loss and 

circulating EPC titer at 6 months FU 

late loss QCA (mm) 

1.70 

1.50 

1.30 

1.10 

0.90 

0.70 

0.50 

1.02 

HEALING II 

0.30 

0.10 

0.53 

-0.10 low EPC 

normal EPC 

0.0 10.0 20.0 30.0 40.0 

( < 6,5 /100 μl) 

( > 6,5 /100 μl) 

number EPC / 100 μl 

R = 0.727

late loss QCA (mm) 

ENDOTHELIAL PROGENITOR CELL CAPTURE 

Correlation late luminal loss and 

circulating EPC titer at 6 months FU 

1.70 

1.50 

1.30 

1.10 

0.90 

0.70 

0.50 

0.30 

0.10 

14/24 2/25 

Statin Tx 

-0.10 

0.0 10.0 20.0 30.0 40.0 

number EPC / 100 μl 

EPC/ 100 μl 

10 

8 

6 

4 

2 

0 

number of EPC/ 100 ul 

12 x 2.0 

5.40 

no statin 

(n=16) 

10.50 

statin therapy 

(n=36) 

HEALING II











or Paclitaxel


DES COMBO with EPC Technology 

EPC capture coating with 

Sirolimus Eluting Stent 

3 DAY – CV16276, 3544 LCX (AB) 


(Cypher 

Select) 

3-Day Porcine Implants 

Virmani/Leon unpublished data 2006





14 DAY – CV16376, 3550 RCA (AB) 


(Cypher 

Select) 



The ultimate dream is to produce a biodegradeable, 

abluminal focused drug eluting (RxTBD), Genous coated 

platform with an additional Rx component integrated 

throughout the polymer backbone 

Abluminal 

Biodegradeable 

Polymer / Rx Matrix 

Polymer Base 

Backbone 

GENOUS Ab 

Coating Matrix 

Rx Component of 

Biodegradeable 

Polymer Backbone 

Matrix

Cut as a metalic Stent 

66



Expansion



Drug Delivery at the 

Abluminal site



Invitro CD34 Cell Capture Activity at the 

endoluminal site

Conclusions 

• Following the 2 pioneers of DES (Cypher and TAXUS), 

various types of new designed coated stents will 

emerge and become available in a few years time. 

• Although these conventional DESs have produced 

promising outcomes, their remarkable effectiveness is 

not yet established for all anatomic subsets. 

• Besides, there are several caveats and concerns about 

conventional DESs (late thrombosis, hypersensitivity, 

abnormal vasomotion, etc). 

• Abolition of neointimal hyperplasia is no longer the 

ultimate goal. Development of more biocompatible 

and bioabsorbable stent facilitating adequate 

endothelialization, is expected in the near future.

Today, we can non-invasively diagnose stenosis with 

MSCT (64, ultrafast) and…Assess non-invasively the 

long-term result of non radio opaque absorbable stent 

Diagnostic 

MSCT 

LCX


Kaneka DES Development Scheme 

Animal Studies at the Thoraxcenter (Complete) 

*To assess safety and efficacy of Tacrolimus DES 

*To find optimum dose (4 arms) 

BMS, Polymer Only, Low Dose and High Dose 

30, 90, 180 days FU for QCA, histology & morphometry 

The results were presented at EuroPCR06 

FIM Trial (will be launched in January 2007) 

Pivotal Trial

BIOABSORBABLE DES 

Today, we can non-invasively diagnose stenosis with MSCT (64, ultrafast) and… 

VR 

VR 

LCX 

Before Stenting 

Apr.24, 2006 

cMIP 

VR 

After Stenting 

Apr.26, 2006 

cMIP 

LCX




Paclitaxel Eluting Stent 


(Taxus Liberté) 








(Taxus Liberté) 



1 Drug with 2 Different Target: Thyrosine Kinase Inhibitors 

2 Drugs with 2 Different Targets: Pimecrolimus-Paclitaxel 

Paclitaxel 

Isoflavone-Sirolimus 

Sirolimus, Biolimus A9 

Everolimus, Zotarolimus 

Cell cycle 

Paclitaxel

NEW BIOLOGICAL TARGET NEW DRUGS-BiolimusA9 

incorporated with the Xtent technology 

Cross lesion 

Begin exposing stents 

Separate at desired stent length 

Inflate 

Retract balloon (option to post-dil) 

Move to next lesion 

Sequence repeated

T-cell activation 

New Biological target New drugs 

PDGF 

FGF 

IL-2 

Sirolimus 

Biolimus A9 

Everolimus 

Zotarolimus 

cytosol 

Blocks T-cell 

prolifelation 

Protein 

Kinases 

- 

Protein Synthesis 

Cdk2, elF-4F, 70-kD S6 kinase 

mTOR 

- 

Inhibit 

p27 

downregulation 

Sirolimus 

upregulation p27 

FKBP 12 

Everolimus 

Biolimus A9 

Zotarolimus 

Calcineurin 

Cell Growth 

G0 

G1 

S 

NFAT 

Cytokines 

M 

G2 

NFAT

#2 DUAL ELUTION ZOTAROLIMUS AND DEXAMETHASONE 

Dexamethasone and zotarolimus 

provide complimentary activity at the 

cellular level 

Anti-proliferative mechanisms 

Anti-inflammatory inflammatory mechanisms 

PC Topcoat + Drugs 

Zotarolimus* + 

Dexamethasone* + PC 

PC basecoat 

*10 ug/mm each

2 Drugs with 2 Different Targets: Pimecrolimus-Paclitaxel 

Paclitaxel 

Isoflavone-Sirolimus 

Dexamethazone-Zotarolimus 

Sirolimus, Biolimus A9 

Everolimus, Zotarolimus 

Cell cycle 

Tacrolimus 

Pimecrolimus 

Paclitaxel 

Isoflavone 

Inhibitor

#2 BIOABSORBABLE DES 

Bioabsorbable DES system 

ML VISION ® SDS 

Polymeric Coating 

Eluting Everolimus

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