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