Drug Coated Balloons From Bench to Bedside
description
Transcript of Drug Coated Balloons From Bench to Bedside
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”