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Drug Eluting Angioplasty Balloons andStents
Dheeraj K. Rajan MD,FSIR
Division of Vascular and InterventionalRadiology
University of Toronto – University HealthNetwork
Interruption of the Cell Cycle:Interruption of the Cell Cycle:
Paclitaxel
Limus DrugsmTOR
pathway
POBA Day 7
Drug-balloon Day 7
JACC Vol. 35, No. 7, June 2000:1969–76J Am Coll Cardiol 2003;42:1415–1420.
Transfer and maintenance of drug in vessel wall:an order of magnitude
Microtubule staining confirmssustained presence of paclitaxel
at 1 week
Microtubule staining confirmssustained presence of paclitaxel
at 1 week
• Following 60-sec dilatation approximately 10%-15% ofthe drug is in the vessel wall 40–60 min later.
• 24 hours later ~10% of drug delivered still resides in vesselwall (1/100 of original dose)
• Following 60-sec dilatation approximately 10%-15% ofthe drug is in the vessel wall 40–60 min later.
• 24 hours later ~10% of drug delivered still resides in vesselwall (1/100 of original dose)
Options Available (within the U.S)
• Drug eluding stents
– Self expanding
• Cook Zilver PTX 6,7,8mm
• Drug eluding balloons
– Bard Lutonix (4-6mm)
– Medtronic InPact Admiral (4-7mm)
• CE approval for avf’s
• Bioabsorbable DES ?
Drug Coated Balloons (DCB):Current Clinical Trials on ClinicalTrials.gov
• 27 studies related to use of DCB technology in the peripheral vasculature in progress :Studies withplanned enrollment ≥100 patients:
NCT Number Study Name Interventions NNCT01587482 PLAISIR PacLitaxel Eluting Balloon Application 100NCT01947478 MDT-2113 SFA MDT-2113 Drug-Eluting Balloon|Standard angioplasty balloon 100NCT02013193 RANGER-SFA Ranger DCB | uncoated PTA balloon 105
NCT01594684
Cotavance Paclitaxel-Coated Balloon VersusUncoated Balloon Angioplasty for Treatment ofIn-stent Restenosis in SFA and Popliteal Arteries
Balloon angioplasty - drug coated balloon (Cotavance, MedradInc.)|drug coated balloon inflation (Cotavance, MedradInc.)|uncoated balloon 112
NCT01305070 FAIR Admiral Xtreme | In.Pact Admiral 118
NCT01366482 DEFINITIVE ARCotavance Drug-Eluting Balloon | TurboHawk/SilverHawk Devicefollowed by a Cotavance Drug-Eluting Balloon 125
NCT02129634 SINGA-PACLI CB-PTA | DEB-PTA 136NCT01175850 INPACT SFA I Drug eluting balloon | standard PTA balloon 150
NCT00986752 ISAR-STATHStenting (Smart Stent) | Stenting after PEB (Smart Stent, Invatec) |Atherectomy (SilverHawk device) 150
NCT01970579 ConSeQuent Paclitaxel coated balloon | uncoated PTA catheter 150
NCT01969630
Paclitaxel-eluting Balloon Angioplasty WithProvisional Use of Nitinol Stent VersusSystematic Implantation of Paclitaxel-elutingStent for the Treatment of Femoropopliteal deNovo Lesions PEB | PES 250
NCT01960647 FREERIDE STUDY PTA with uncoated balloon | PTA with Paclitaxel balloon 280
NCT01858363CVI Drug Coated Balloon European RandomizedClinical Trial
CVI Paclitaxel-coated PTA Balloon Catheter | Bare PTA BalloonCatheter 360
NCT01858428 ILLUMENATE PivotalCardiovascular Ingenuity (CVI) Paclitaxel-coated PTA BalloonCatheter | EverCross Balloon Catheter 360
NCT01566461 INPACT SFA IIIN.PACT Admiral Drug-Eluting Balloon | Standard angioplastyballoon 450
Global Study of a Drug-coated Balloon to Treat Source: ClinicalTrials.Gov. June 2014.
Summary
• DEB – efficacy
– Improved late lumen loss up to 12 months
– Better binary restenosis rates to 5 years
• DEB – clinical outcomes
– No advantage for amputation
– Rutherford score
– mortality
Disease process
• Atherosclerotic plaque
– Contains lipids, dead cell debris
– Macrophages, t cells and mast cells
• Intimal hyperplasia
– Smooth muscle cells
– Extracellular matrix
Disease Process
• Veins are different than arteries
• Also
– Thinner internal elastic lamina (sm cell migration)
– Higher fibroblast growth factors
– Shear stress
– uremia
1
3
5
7
9
1
1
53
7 9
ePTFE Graft
Vein
JVIR 2014; 535
• Randomized
• Paclitaxil balloons 4 mm size
• Avf’s juxta-anastomotic tandem stenoses
• 10 patients acted as their own controls– 20 lesions
• TLR freedom 251 vs 103 days
• Patency 70% vs 0% 6 months (p>0.01)
• No difference at 12 months
• (sample size-pilot)
JVIR 2015;348
• Single center randomized – one year f/u
• Medtronic 4-7mm paclitaxel
• 40 AVF patients – sample size calculated
• Device success
– 100% poba; 35% deb – needed f/u POBA
• TLR 308 d vs 161 d (p=0.03)
• Primary access patency
– 270d vs 161d (p=0.04)
• (visual estimation, F/u)
JVA 2015;388
• Retrospective; 37 lesions treated w paclitaxelDEB (medtronic 4-7mm)
• all in-stent stenosis (3 were immature fistulas)
• Looked at patency pre deb intervention to postdeb intervention
• 69% versus 19% at one year (? P val, lesion)
• (F/u, measurements 30/50%)
JVA 2014; 338
• 26 patients – prospective
• Radiocephalic juxta-anastomotic lesions
• PTA then DEB
• Assessed w echo and venography
• lesion primary patency
– 96% 6 months; 91% at 12 months
• (who evaluated)
Current Trials
Food for thought
• Ideal dose has not been determined
• Ideal excipient has not been ascertained
• Ideal location for delivery of drug has not beenascertained
• Ideal dwell time has not been ascertained