Drug Coated Balloons

From Bench to Bedside

Service de Radiodiagnostic et Radiologie InterventionnelleUniversité de Lausanne

Salah D. Qanadli, MD, PhD, FCIRSECardio-Thoracic and Vascular Unit, QMI Lab

Department of RadiologyCHUV-University of Lausanne

Potential Conflict of Interest

• Educational grants– Cordis, Boston Scientific, Medtronic, Invatec, Bard

• Research grants– Abbott Vascular, Biotronik, Cordis, St Jude Medical

• Consultancy– Mediar Ltd.– University of Kingston London– Cook, Optimed, Cordis, Bard, Abbott, Terumo– Bioclinica

Dotter’s Predictions in World’s First PTA*

– Balloon angioplasty– Recanalization devices– Outpatient PTA– Cost saving relative to surgery– Endovascular “splints” (stents) that “reintimalize” (endothelialize)

Dotter et al., Circulation, 1964

PTA in 2013 for PAD

• Critical issues– Immediate technical results

- Immediate out-come- Flow limiting dissection- Elastic Recoil

- Immediate technical success- CTO recanalization

– Re-stenosis (mid and long-term patency)

DCB Technology

DCB Mechanism of Action

1.30-second minimum inflation transfers drug to endoluminal surface

2.PTX diffuses into the arterial wall from an endoluminal reservoir

3.Over time, therapeutic drug levels are sustained in deep cell layers after endothelial drug levels become sub-therapeutic

4.Drug continues to inhibit restenosis in arterial wall while allowing the lumen to restore and re-endothelialize

LUTONIX Pre-clinical data

Coating uniformity

• European Product, Data on file. • 6x60 mm Lutonix Drug Coated Balloon – N=5• 6x60 mm In.Pact Admiral-Paclitaxel-eluting PTA balloon catheter –

N=5

Defining Indications for DCB

• Clinical needs• Device availability• Proof of concept• Clinical evaluation• Strategy for use/Cost-effectiveness

Defining Indications for DCB

• Clinical needs– Clinically driven concept

- High risk of re-stenosis- Femoro-popliteal lesions

- up to 60 % at 12 mo*- Small vessels BTK

- up to 69%**- AV Dialysis access

- Re-stenosis/occlusion up 62 % at 12 mo***

*Muradin GS et al., Radiology, 2001.**Krokidis M et al., Cardiovasc Intervent Radiol, 2012.***Bittl JA, JACC Cardiovascular Interv, 2010.

Defining Indications for DCB

• Clinical needs- Clinically driven concept

- Limitations of existing alternatives (Stents, including DES) - BTK ?- BTA- AV shunts- FP- ISR- Complex anatomy (bifurcations, trans-collateral approaches,…)- Over dependence of double anti-agregants

Defining Indications for DCB

• Technology safety/efficacy– Proof of concept

- Paclitaxel coated balloon (PCB)- DCB in routine practice in 2013 is PCB !

• Clinical evaluation– Level of Evidence

• Cost-effectiveness– Strategy for use

De-Novo Femoro-popliteal Lesions

N=433 pts Uncoated B Paclitaxel CB p

TLR (n=350) 27.7 % 12.2 % <0.00001

RR (n=233) 45.5 % 18.7 % <0.0001

LLL (n=307) 0.61-1.7 mm -.05-.05 mm <0.00001

Mortality (n=358) 4.8 % 2.1 % 0.95

Adjunctive Stents (cross over)

14 to 34 % 4 to 21 %

THUNDERFemPac

LEVANT IPACIFIER

Control arm: UB !Median FU: 10.3 moExclusion: Severely impaired arterial out flow

BTK Lesions

BTK RCT Target segment Arms PE/FU Nb Pts Estimated completion

PICCOLO BTK PCB vs UB 6 mo-18 mo 114 April 2011

IN.PACT DEEPNCT00941733

BTK PCB vs (UB+pStent)

12 mo 357 December 2015

DEBATE BTK BTK PCB vs UB 12 mo 150

DEBELLUM SFA/BTK PCB vs UB 6 mo 50

EURO CANALNCT01260870

BTK PCB vs UB 6 mo 120 December 2017

AV Dialysis Access

6 mo Uncoated B Paclitaxel CB p

Primary patency rate 25 % 70 % <0.001

In-Stent Re-Stenosis

Ongoing ISR RCT Target segment

Arms FU Nb Pts Estimated completion

FAIRNCT01305070

SFA ISR PCB vs UB 6 mo (DUS) 118 June 2013

ISAR PEBISNCT01083394

SFA ISR PCB vs UB 6 mo 70 July 2013

PACUBA INCT01247402

SFA/PPA ISR PCB vs UB 12 mo (DUS, CTA) 60 December 2012

Who is the best candidate for PCB ?

Clinicallly driven concept

Dedicated material

Proof of conceptEvidence based Paractice

Srategy for use/Cost-Effectiveness

SFA de-novo

Clinically driven concept

Dedicated material

Proof of conceptEvidence based Paractice

Strategy for use/Cost-Effectiveness

Clinically driven concept

Dedicated material

Proof of conceptEvidence based Paractice

Strategy for use/Cost-Effectiveness

Clinically driven concept

Dedicated material

Proof of conceptEvidence based Paractice

Strategy for use/Cost-Effectiveness

AV Dialysis AccessISR

BTK/BTA

What doses the future hold ?

Clinicallly driven concept

Dedicated material

Proof of conceptEvidence based Paractice

Srategy for use/Cost-Effectiveness

SFA de-novo

Clinically driven concept

Dedicated material

Proof of conceptEvidence based Paractice

Strategy for use/Cost-Effectiveness

Clinically driven concept

Dedicated material

Proof of conceptEvidence based Paractice

Strategy for use/Cost-Effectiveness

Clinically driven concept

Dedicated material

Proof of conceptEvidence based Paractice

Strategy for use/Cost-Effectiveness

AV Dialysis AccessISR

BTK/BTA

“Good judgment is based on experience

Martin J. Lipton

andexperience is based on bad judgment”