DRUGELUTINGBALLOON

ELUTAX

Dr.med.AlexanderRuebben

DRUGELUTINGBALLOON

WHY?

Dr.med.AlexanderRuebben

UNSOLVEDDESPROBLEMS

•  IN‐STENTRESTENOSIS•  BIFURCATIONS•  SMALLVESSELS

•  DIABETES•  ACUTEMI

NewEngJMed2006,355:2113‐24

ADVANTAGESOFTHENEWTECHNOLOGY

•  ONESHOTDRUGAPPLICATION•  NOTRIGGERTOFOREIGNBODYREACTIONDUETOSTENT

•  NODISTORTIONOFORIGINALVESSEL„BIF“•  NOINFLAMATIONDUETOPOLYMER

•  NOMULTIBLESTENTLAYERSINBIFURCATIONSORIN‐STENTRESTENOSIS

Hwang, Circulation 2001; 104: 600-5

Homogenous Drug transfer!

PaclitaxeldeliverythroughDESVERSUSDEB

SchellerPaccocath

Effects of Paclitaxel

After dilatation we have maximum drug dose at the

vessel wall, which can be measured for min. 2 days.

However the Drug action persist for at least 2 weeks

Axel, D. I. et al. Circulation 1997;96:636-645

Copyright ©1997 American Heart Association

Axel, D. I. et al. Circulation 1997;96:636-645

Immunofluorescence micrographs demonstrating the effect of 1.0 micromol/L paclitaxel on the distribution of the contractile filament smooth muscle {alpha}-actin and the intermediate filament vimentin in haSMCs

Axel, D. I. et al. Circulation 1997;96:636-645

Immunofluorescence micrographs showing the effect of 1.0micromol/L paclitaxel on cytoplasmic microtubule distribution

Disrub[onofmicrotubuli

LESSONSLEARNEDTILLTODAYPUREPACLITAXELWITHOUTANYMATRIXOR

ADDITIVEISNOTOPTIMAL!

CremersDGK2008

However‐Dior1genera[on:StellaPCR09

WHICHTECHNIQUEISUSEDTODAYtoFreePaclitaxelandtoensureUp‐take

• MixtureofPaclitaxelwithHydrophilicandLipophilicAddi[ve:

• SequentPlease‐BBraun•  In.PactAmphirion‐Invatec

• MixtureofPaclitaxelandShelacsolu[on• DIOR(2ndGen)‐Eurocor

• MatrixofpurePaclitaxel„Ice“and„Snow“• ELUTAX–AachenResonance

Whatdoesthismean?

•  Amixtureofdifferentcompoundswithpaclitaxelguaranteesadiffusionfromtheballoonandanuptakeintothevessel

DrawBack!!!!

•  Thereleasebeginnsoncethecatheterisincontactwithfluids!!!!!!!!

•  Theamountofdruguptakedependsonthedura[onoftheprocedure!

ELUTAX

•  Homogenouscoa8ng

•  EvenandConsistentcoa8ngofinflatedBalloons•  DrugMatrixofpurePaclitaxel(twolayersSNOWandICE)

•  Balloonwith360Degreecoa8ngcoverage•  MinimalDruglostduringpassageinthebody

•  MinimalDruglostfromtheballoonsurfaceduringmaneuverorinfla8on

•  Reliablequan8ta8veDrugdeposi8onintothevesselwall•  SafeDrugTransfer•  Noaddi8onalsubstances•  NoCracks

WhichDrugdose?2or3microgramm/mm2

WhatmaSersisnotthedrugdoseontheballoonbuttheDrugwhicharrivestothevesselwall!!!!

12h 0,19 9,80 7.79 8,08 0,74

proximalreference

proximaldilatedsequence

distalreference

middledilatedsequence

distaldilatedsequence

1 2 3 4 5

1 2 3 4 5µmol/l

Arterial[ssuepaclitaxelconcentra[onamerELUTAXballoondilata[on

1h 6.9 58,7 66,2 79,2 7.0.

proximalreference

proximaldilatedsequence

distalreference

middledilatedsequence

distaldilatedsequence

1 2 3 4 5

1 2 3 4 5 µmol/l

ELUTAX

Gyöngyösi

Pharmacokinetics of ELUTAX

1min60min12hours

Dior1gen.

Elutax2ndgen.

0

50

100

150

200

250

1 2 3 4 5

Foratleast12hourswehaveatherapeu[cdoseinthevesselwall!

Gyöngyösi

([ssueconcentra[onofpaclitaxeleffec[vefrom56nMto50µM,toxiceffectover100µMincellculture,Axeletal.Circula.on1997)

Gyöngyösi

StellaPCR09

Productswithtoxic[ssuePaclitaxelconcentra[onlongerthanonehour

SequentPlease

Diorcurrentcoa[ng

([ssueconcentra[onofpaclitaxeleffec[vefrom56nMto50µM,toxiceffectover100µMincellculture,Axeletal.Circula.on1997)

SequentPlease

EurocorDIORnewcoa[ng

WhichProblemscanoccur,iftootoxicDrug‐levelsareapplied:?

Differentaspects:Coa[ngtechnique

•  EUROCOR,INVATECandBBraun,arecoa[ngafoldedBalloon!

•  AACHENRESONANCEcoatstheinflatedballoon

Seethedifference

Exampleforunevencoa[ng:NewDIORBALLOON

Totallyunevenwithbigcrystals,nearlynoPaclitaxelinFolds

OpeningBehaviorofDifferentBalloons:

ELUTAX

Mul[pleDrugDebrisarefallingoftheBalloonduringInfla[on!

Mul[pleDrugDebrisarefallingoftheBalloonduringInfla[on!

ELUTAX

NODrugDebrisarefallingoftheBalloonduringInfla[on!

Results

Mul8pleDrugdebrisarelostduring

Infla8on

Mul8pleDrugdebrisarelostduring

Infla8onNODruglost!

MinimalDrugcontentoninflatedBalloon

Onlypar[aldrugloadremainsonthe

Balloon

Fullyloadedballoonreachesthevessel

wall

Drugdebrismaybedangerouscausingdistalembolism

Drugdebrismaybedangerouscausingdistalembolism

SAFE!

UNIVERSITÄTSKLINIKUM DES SAARLANDES

NewFron[ers:renalarteryTreatmentofIn‐stentRestenosiswithELUTAX

Prof.Reul,BetaKlinik,Bonn

NewIndica[ons

5MonthAngioandMRFollow‐up

NosignofRestenosis!

Dialysis Patient

42 years

UNIVERSITÄTSKLINIKUM DES SAARLANDES

NewIndica[ons

IasisCE‐trial(Bulgaria)In‐Stentrestenosis,withangiographicfollow‐up

amer6months:

performedbyDr.IvanManukov,HeadofDepartmentIntervenDonalCardiology,UMBALSveDGeorgiHospital,Plovdiv,

Bulgaria

43pa[entstreatedwithElutax0%restenosis