CORONARY STENTS yStent DR KRISHNA KUMAR. K MD DM FACC.

CORONARY STENTS

yStent

DR KRISHNA KUMAR. K MD DM FACC

BrachytherapyCutting BalloonDirectional AtherectomyExtraction AtherectomyLaser AtherectomyPerfusion BalloonRotational Atherectomy

19771977

20112011

Balloon Angioplasty ( March 1977)Balloon Angioplasty ( March 1977)

Bare Metal Stent (1986)Bare Metal Stent (1986)

Drug Eluting Stent (2002) Drug Eluting Stent (2002)

11stst Gen Gen

Drug Eluting Stent (2002) Drug Eluting Stent (2002)

11stst Gen GenAngioscopyDoppler Flow

Intravascular UltrasoundOptical Coherence

TomographyPalpography

Pressure MeasurementsThermography

Virtual Histology

Drug Eluting Stent (2005) Drug Eluting Stent (2005) 22ndnd gen gen

Drug Eluting Stent (2005) Drug Eluting Stent (2005) 22ndnd gen gen

Historical Overview

• 1967 - Coronary Artery Bypass Graft Surgery (CABG)• 1977 - Percutaneous Transluminal Coronary Angioplasty (PTCA)• 1978 - Idea of stent conceived• 1987 - First balloon expandable stent (Palmaz-Schatz™) implant in

human coronary artery• 1992 - Julio Palmaz and Richard Schatz: If you could only

coat this stent with a drug…..• 1993 - Introduction of Coronary Stents (BiodivYsio PC polymer

coated stent)• 2002 - Cypher Drug-eluting Stent• 2003 - Taxus Drug-eluting Stent• 2005 - Endeavor Drug-eluting Stent• 2006 - Xience V Drug-eluting Stent• 2007 - Endeavor Sprint, • 2008- Endeavor Resolute and Promus Drug-eluting Stents• 2009- Biodegradable polymer stents• 2010- Bioabsorbable stents• Future – Integrity- Newer generations of Bare-metal Stents and Drug-eluting Stents

1977

• Gruntzig – Plain balloon angioplasty.

• Dissection and acute vessel closure

• Recoil

• Restenosis

• In 1986, working in Toulouse, France, Jacques Puel and Ulrich Sigwart implanted the first stent into a human coronary artery

In 1986, working in Toulouse, France, Jacques Puel and Ulrich Sigwart implanted the first stent into a human coronary artery

TLR – 28%

TVR – 38%

2% ST

BVS Needs a drug to prevent restenosis

Type of Drug

Type of Polymer

Stent DeliverySystem

Stent Platform

The Four Key Components of STENT DesignScientific Design & Integration

Approach to Stent Material-ALLOY

• A new stent material had to meet all of the following requirements:

• L-605 cobalt chromium and 316L stainless steel have a protective chromium oxide layer and similar biocompatibility.

• Because of the different element mix, cobalt chromium is stronger and more radiopaque than stainless steel.

Cobalt Chromium Compared to Stainless Steel

Cobalt Chromium Strength• Cobalt chromium is 76% stronger than stainless

steel.• Strength of cobalt chromium allows cc stent to

have thin struts while maintaining better radial strength.

New alloy• Properties of Platinum Chromium:

• Over 2 times more dense than Iron or Cobalt, providing superior radiopacity

• Increases strength when alloyed with 316L Stainless Steel

• Vascular compatibility

• Platinum Chromium takes strength, flexibility & radiopacity a generation beyond Cobalt Chromium.

Advantages• Radial strength,

• Exceptional deliverability • Hgh visibility.

• The thin-strut stent is designed for improved conformability, minimal recoil and uniform lesion coverage and drug distribution.

• The advanced low-profile delivery system, coupled with the

radiopacity, facilitates precise delivery of the stent across challenging lesions.

Connecting Link

Terms

Element Length

Crests

Ring

Crests per Ring

1

23

54

1

2 3

5

4

6

6 Crests per Ring

5 Crests per Ring

Crests per Ring• Less Crests More Crests

• Less Scaffolding More Scaffolding

• Easier to reduce profiles

• Less Expansion Range

1

2

3

4 5

12

34

6

Connections per Ring• Less More• More Flexible Less Flexible• Less Scaffolding More Scaffolding

Element Length• Shorter

• Better scaffolding• Higher radial strength

• Wider• Poorer scaffolding

• Lower radial strength

Stent Struts

• Strut Thickness– Distance from the

inner stent surface to the outer stent surface

Width

Thickness

Thin Strut Advantage Reduce deep wall trauma

18%15%

31%26%

0%

5%

10%

15%

20%

25%

30%

35%

ISAR STEREO 1 ISAR STEREO 2

ThinMulti-link®

Thick

Strut thickness appears to have a significant impact on long-term restenosis after stent implantation.1,2

6-month binary restenosis

ThinMulti-link®

Thick

Strut Thickness TradeoffThinner

Less Visible

Less Metal in the Vessel

ThickerMore Visible

More Metal in the Vessel

Radial strength

is generally defined as the pressure which a stent exerts to the vessel or lumen into which it is implanted.

Longitudinal Foreshortening

Peak to peak

Peak to Valley connector

Offset peak-to-peak

Four Stent Design Families

Peak-to-valley

Peak-to-peak

Mid-strut connector

Element platform

Driver platform

Integrity platform

Juno platform

Nobori platform

Veriflexplatform

ProNova platform

Cypher Select platform

Coroflex Blue platform

PRO-Kinetic Energy

platform

MULTI-LINK VISION platform

MULTI-LINK 8 platform

Firebird2 platform

Express2platform

Images on file at Abbott Vascular.

Synergy platform

Promus Premier platform

Information contained herein is not intended for physicians from France or the United States.©2013 Abbott. All rights reserved. AP2938378-OUS Rev. B 04/13

1.3 1.4 1.62.6 2.5 2.9 3.2

4.65.3

1.82.7 2.8

3.6

13.2

0

2

4

6

8

10

12

14

XIENCEPRIME

0.0032 inCoCr

XIENCE V 0.0032 in

CoCr

TAXUSExpress 0.0052 in

SS

Firebird20.0034 in

CoCr

Endeavor(Driver)0.0036 in

CoNi

Nobori0.0054 in

SS

IntegrityResolute 0.0036 in

CoNi

BioMatrix Flex

0.0054 inSS

TAXUSLiberte 0.0038 in

SS

CypherSelect+0.0055 in

SS

PRO-KineticEnergy

0.0024 inCoCr

Coroflex Blue

0.0026 inCoCr

ProNOVA0.0024 in

CoCr

Element 0.0032 in

PtCr

Lo

ng

itu

din

al s

ten

t c

om

pre

ss

ion

(m

m)

81 mm81 mm

132 mm86 mm

91 mm137 mm

91 mm 137 mm 97 mm 140 mm

61 mm

66 mm61 mm 81 mm

Bench Testing: Longitudinal Stent Compression

Effect of Stent Design

Weaker

Stronger

Peak-to-valley designs Mid-strut connector designsOffset peak-to-

peak designPeak-to-peak designs

Amount of longitudinal compression under 50 gf

Tests performed by and data on file at Abbott Vascular.


What can result from LSD? The Spectrum of Adverse Events

Poor lesion coverage

Plaque prolapse

Post-dilatation of deformed stent

Difficulty re-entering stent for post dilatation

Additional stenting

Prolonged procedure as a result of additional intervention

Stent thrombosis

Restenosis

Increased vessel injury

Lack of tissue or lesion coverage

Dissection

Death

Cardiac surgery

Procedural Events Post-Procedural Events

1. Mamas, M. EuroIntervention, March 2012. 2. Williams, P. EuroIntervention, Oct. 2011. 3. Source: Bartorelli et al., Stent longitudinal distortion: strut separation (pseudo-fracture) and strut compression (“concertina” effect), EuroIntervention June 2012. 4.Stone, G. Everolimus-Eluting Stents 2011/2012 Stent Design Evolution and Clinical Trial Update, TCT 2011. 5. Leibundgut, G et al. Longitudinal Compression of the Platinum-Chromium Everolimus Eluting Stent During Coronary Implantation. Catheterization and Cardiovascular Interventions. Accepted Article. Doi 10.1002/ccd.24472.

Leibundgut, PCR 2012

OCT image showing stent crowding as a result of LSD5


Reported Clinical Events from Longitudinal Stent Deformation1,2,3,4:

Stent Platform Characteristics

• Struts thickness– Thinner struts result in:

• Lower profile stent• Improved flexibility of the stent

• Strut geometry– For DES, the greater the surface area, the higher the quantity of drug that can be

bound and delivered to target tissue.

• Material / composition– Common stent materials include stainless steel, cobalt alloy,

nitinol, tantalum.

• Cell area

• Cell design (Open versus Closed Cell)– Open cell design offers less coverage but more flexibility, side branch access and

conformity to the vessel wall.– Closed cell design offers more coverage for large plaque burden but less flexibility.

Stent Design Summary

Improve Scaffolding: More crests per ring• Shorter element length• More connections per

ring

Improve Flexibility:• Shorter element length• Less connections per

ring• Shaped or staggered

connections

Visibility:• Thicker struts

Profiles:• Thinner struts• Less crests per ring

• Expansion Range:• More crests per ring

Metal in Vessel:• Thicker struts• More crests• Shorter element length

Stent Delivery System

• Balloon-expandable – Factory mounted on a

balloon delivery system

• Self-expanding– Stent placed under a sheath– Sheath retraction allows

stent expansion

Balloon material - determines control of stent expansion and trackability.

Balloon Markers (visibility/location) - provide for ease and accuracy of stent placement.

Discrete Balloon length - minimum balloon overhang post deployment and aid in reducing potential risk of edge dissection.

Stent Security – describes the ability of the stent to stay on the delivery system, especially in tortuous trackability or during system withdrawal.

Additional Stent Design Considerations

An Ideal Stent Delivery System

Minimal Balloon Overhang

Stent Platform - Xience V and Promus DES

• Stent platform - Multi-link Vision• Slotted tube design• Cobalt Chromium – increases strength and visibility• Open-cell design enhance vessel conformability

Information available on company website and subject to change

Stent Platform – Endeavor/Sprint, Endeavor Resolute DES

• Stent platform – Driver• Modular design - thin, edgeless struts enable atraumatic delivery• Cobalt alloy composition increases strength and visibility• Open-cell design and short modular elements enhance vessel conformability

Earlier Generation Medtronic Stents

The Preferred Mechanism of Action (MOA)

The drug would ideally act early in the G1 phase, preventing entry into the S phase

G2

M

G0G1

S

CellCellcyclecycle

G0:G0: Resting (zero) stateResting (zero) state

G1:G1: Cell clears Cell clears ““checkpointscheckpoints”” in in readiness to greadiness to grow and prepare row and prepare chromosomes for replicationchromosomes for replication

S:S: DNA duplicatesDNA duplicates

G2:G2: Cell duplicates organelles, Cell duplicates organelles, prepares for Mprepares for M

M:M: Cell physically dividesCell physically divides

2 Drugs with 2 Different Targets: Pimecrolimus-Paclitaxel

Isoflavone-SirolimusDexamethazone-Zotarolimus

TacrolimusPimecrolim

us

Sirolimus, Biolimus A9 Everolimus, Zotarolimus

Isoflavone Inhibitor

Paclitaxel

Smooth Muscle Cell Mechanism of Action (MOA)

Some drugs are cytostatic and stop proliferation before the cell is committed to division

Ideal Drug for DES

All illustrations are artist renderings.

Proven Clinical Performance

– Efficacious

– Safe in systemic uses

Preferred Mechanism of Action (MOA)

– Cytostatic

– Non-inflammatory

Wide Therapeutic Window

– Excellent tissue compatibility

– Effective at multiple doses with minimal toxicity

Drug Stability

– Product yield (manufacturing)

– Shelf-life

Polymers

• Durable (permanent polymer)

• Bio-degradabale polymer

Polymer Coating Configurations

Stent

Stent

StentMatrix Only Design

Primer and Matrix Design

Primer, Matrix, and Topcoat

Design

Primer: May be applied to improve adhesion to stent

Matrix Coating: Mixture of drug and polymer

Topcoat: May be applied if needed to slow the release rate of the drug

High Drug Loading Capacity

A polymer with a high drug loading capacity, allows for a thin polymer coating

Polymer Thickness

on outer diameter (O.D.)7.8 µm

System Crossing Profile

.041"

7.8 µm

Directional Drug Delivery(abluminal preference)

• Selective coating on the

outside surface of the stent– Reduced drug/polymer– Luminal surface BMS– Drug only where needed

Properties of an Ideal DES Polymer

Hemocompatibility

– Non-thrombogenic and non-inflammatory

– Proven in other blood contacting applications

Controlled release of the drug

– Release throughout the restenosis cascade

– Complete release of drug over time

High drug loading capacity

– Thin coating thickness

– Minimizes crossing profile

Uniform Coating Integrity

– Toughness for coating integrity during delivery

– Elastic for coating integrity upon expansion

Adhere to the stent, but not the balloon

Can we do away with the polymer?

Polymer free drug-delivery

Do we need a scaffold permanently?

Late Disease Progression

Accelerated by the Presence of a Stent?

1Guiteras-Val, P., et al. Am J Cardiol. 1999;83:868-874. / 2Hatrick, R., et al. EuroIntervention. 2009;5:121-126. / 3Kimura, T., et al. Circulation. 2002;105:2986-2991.

Disease Progression: PTCA versus BMS

The Clinical Need for a Bioresorbable Vascular Scaffold

RationaleVessel scaffolding is only needed transiently*Vessel scaffolding is only needed transiently*

Vision

Potential Benefits

Rationale

Vision

Potential Benefits

Improve Long Term Outcomes for Patientsby Leaving No Scaffold Behind1

Improve Long Term Outcomes for Patientsby Leaving No Scaffold Behind1

Restore the vessel to a more natural state, capable of natural vascular function

Eliminate chronic sources of vessel irritation and inflammation

Vessels remain free for future treatment options (i.e. CABG)

Reduce the need for long-term DAPT2

Allows for use of non-invasive imaging techniques (CCTA)

Improve patient quality of life

Restore the vessel to a more natural state, capable of natural vascular function

Eliminate chronic sources of vessel irritation and inflammation

Vessels remain free for future treatment options (i.e. CABG)

Reduce the need for long-term DAPT2

Allows for use of non-invasive imaging techniques (CCTA)

Improve patient quality of life

*Serruys PW, et al., Circulation 1988; 77: 361. Serial study suggesting vessels stabilize 3-4 months following PTCA.1 – Small platinum markers at scaffold edges remain for fluoroscopic landmarking. 2. The Absorb IFU recommends DAPT for a minimum of 6 months.

Lactate

KrebsCycle

H2O

CO2

Scaffold Strut

DIFFUSION

Lactic Acid Lactate

Intracellular Mitochondrion

Lactic acid is readily converted to lactate, a common fuel source for multiple

metabolic pathways1

Lactic Acid

Resorb: Absorb is Resorbed by a Natural Process

BioMime MorphTM - Sirolimus Eluting Coronary

Stent System

Device Description Unique tapered coronary stent. Tapering diameters (1/2 sized)

Distal to Proximal – 3.50→3.00 mm & 3.00→2.50 mm

Longest lengths – 50, 60 mm Mounted on a newly created extra support Rx balloon

catheter with tapered diameters 1.25 µg/mm2 of Sirolimus, 30-days release kinetics. Biodegradable polymer base

Ø 3.50Ø 3.00

Proximal l – 50, 60 mm Distal

Ø 3.00Ø 2.50

Ø 3.50Ø 3.00

Ø 3.00Ø 2.50

= D1

= D2

D1 > D2

Actual device photographs. Data on file Meril Life Sciences.

Unmet Clinical Need A stent that matches the diameter differentials from

distal to proximal in long diffused lesions. One & done.

NEW DESIGNS

• M –GUARD

• STENTYS

• DEDICATED BIFURCATION STENTS

• Endothelial progenitor cell capturing stent

Pro-Healing approach

• Endothelial progenitor cells have been identified as a key factor in the re-endothelialization process after stent implantation.

• Orbus

• HEALING – II Study

Surfaces to Encourage Cell GrowthBioactive surfaces to accelerate functional endothelialization

Orbus – EPC Capture cell

drugpeptide

protein

device surface

Peptide linkers

Cell specific peptide linkers (Affinergy)

Nanotextured Surfaces

Example of IrOx

What will be the future?DES

Thin strut Bio-absorbable radio-opaque scaffold.

Potent limus group of drug / multiple drugs.

Non-polymer drug delivery, nano particle based.

Focus will be on Prohealing and fast re-endothelialization

Dedicated stents for bifurcations and small vessels

Definitely we can expect more….

Thank You

CORONARY STENTS yStent DR KRISHNA KUMAR. K MD DM FACC.

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Transcript of CORONARY STENTS yStent DR KRISHNA KUMAR. K MD DM FACC.