current status of drug eluting balloons for sfa/pop intervention

CURRENT STATUS OF

DRUG ELUTING

BALLOONS FOR

SFA/POP INTERVENTI

ONBY

M. AKRAM KHAN MD FACC FSCAI

FINANCIAL DISCLOSURE

None

WHY DRUG ELUTING BALLOON FOR SFA/POP DISEASE

PTA High rate of restenosis (40 – 60%)

DEBULKING DEVICE

High rate of restenosis / high rate of stent deployment

BMS ISR – 30-50% (RESILIENT TRIAL)

COVERED STENTS

Same Issue, 1 year patency 40 -80%

DES Same Issue, not like coronary DES (SIROCCO II TRIAL), (ZIVER PTX), (Everolimus)

ISSUES WITH SFA/POP RESTENOSIS

Long lesions, complex morphology, frequent multi levelLow flow ratesCalcificationUneven delivery of local drug Stent fracturePolymer induced inflammationConstant bio-mechanical pressure due to body movement

HISTORY OF DEBINVENTORS

1979 – Professor Speck invented contrast agent Ultravist (iopromide)2001 – Both Prof. Speck and Prof. Scheller introduced Ultravist / Paclitaxel Paccocath balloon

Paclitaxel with Spacer which was

iopromide

Paccocath Balloon B. Braun

Cotavance BalloonMEDRAD

Dr. Bruno Scheller

(Interventional Cardiologist)

Professor Ulrich Speck

(scientist)

PACLITAXEL IN DEBHow does it work

Local Dose: 300 – 600 µg (100 – 200 µg in DES) which is 300 times less compare to systemic administration.

Immediate Release

Short acting exposure

No Polymers

Cytotoxic which inhibits G2 phase of Mitosis

Spacer / Excipient which facilitates local delivery

PACCOCATH TECHNOLOGY DESCRIPTION

Paclitaxel+Hydrophilic Spacer (iopromid

e)

FIRST GENERATI

ON BALLOON

Current Drug Coated Balloons on the Market

Peripheral and coronary DCBs with CE MarkCompany Device Name Balloon

Drug LoadCarrier

Lutonix Moxy DCB 2 µg/mm² Non- plymericMedrad-Possis Coatavance 3 µg/mm² Lopromide

Medtronic/Invatec In.Pact 3.5 µg/mm² Urea

Biotronik Pantera Lux, Passeo 18

3 µg/mm² BTHC

B. Braun Sequent Please 3 µg/mm² Lopromide

Eurocor DIOR II, Freeway 3 µg/mm² Shellac

Aachen Resonance

Elutax 3 µg/mm² Unknown

Blue Medical Protege 3 µg/mm² Unknown

FIRST GENERATION LANDMARK TRIALS

THUNDER TRIAL

FEMPAC TRIAL

THUNDER & FEMPAC TRIAL 6 MONTHS RESULTS

No. of patients FEMPAC TRIAL THUNDER TRIAL

    Uncoated 42 54

    Coated 45 48

6-mo late lumen loss, mm

    Uncoated 1.0±1.1 1.7±1.8

    Coated 0.5±1.1 0.4±1.2

6-mo angiographic restenosis, %

    Uncoated 47 44

    Coated 19 17

6-mo % TLR

    Uncoated 33 37

    Coated 9 4

18–24 mo % TLR

    Uncoated 48 52

    Coated 20 15

6-mo major amputations

    Uncoated 2 0

    Coated 0 2

THUNDER FIVE YEAR OUTCOMEFreedom from TLR: Kaplan-Meier

FEMPAC 2 YEAR OUTCOMEPAC Balloon Vs. Control

Follow up 18 and / or 24 Months

NEXT GENERATION TRIALS

Lutonix Paclitaxel-Coated Balloon for the

Prevention of Femoro popliteal Restenosis Trial

for Femoro popliteal Revascularization

A Randomized Multicenter Trial Evaluating Prevention

of Restenosis with Paclitaxel-

Coated PTA Balloon Catheters in

Stenosis or Occlusion of Femoro popliteal Arteries

LEVANT-I PACIFIER

LEVANT-I 6 MONTHS RESULTS

PACIFIER – 6 MONTHS ANGIOGRAPHIC FOLLOW UP

DEB Control P value% Diameter Stenosis % 28.6% 40.4% 0.01Min. Lumen Diameter

mm3.6 mm 3.0 mm 0.03

Binary Restenosis n/N (%)

4/40 (10%) 12/39 (31%) 0.03

Late Lumen Loss mm -0.05 mm 0.61 mm 0.003

METANALYSIS OF DEB RANDOMIZED TRIALS

Conclusion: Consistent with statistically significant lower rate of restenosis in DEB Trials.

FIRST DEB VS PTA TRIAL IN USA(APRIL 2014)

IN.PACT SFA TRIAL- ONE YEAR DATA331 PATIENTS FROM EUROPE AND THE US RECEIVED A DRUG-ELUTING BALLOON (DEB;

N=220) OR ANGIOPLASTY (N=111)

Conclusion: The IN.PACT Admiral DEB achieves substantially better primary patency at 1 year

compared with angioplasty.

ITT Analysis at 1 Year

DEB (n=220)

Angioplasty (n=111)

P Value

Primary Patency 82.2% 52.4% <0.001

Clinically Driven TLR 2.4% 20.6% <0.001

Primary Sustained Clinical Improvement

 85.2%

 68.9%

Primary Safety Endpoint

95.7% 76.6%

MACE 6.3% 24.3%The primary safety composite (freedom from 30-day device-

and procedure-related death and from target limb major amputation and clinically driven TVR through 12 months) was

higher in the DEB arm.

CURRENTLY ONGOING USA TRIALS ON DEB

LEVANT-IIIN.PACT SFA IIDEFINITIVE - AR

(ENROLLMENTS EITHER COMPLETE OR NEAR COMPLETION)

DEB VS PTA FOLLOWED BY STENTING- DEBATE SFA TRIAL

12-month Restenosis and TLR (per lesion)

12-month Major Adverse Event

Restenosis per lesion length Restenosis per Revasc Technique

DEB VS DESINPACT VS ZILVER PTX

1. Single Center2. Retrospective with

Propensity Score analysis

3. IN.PACT DEB vs Zilver PTX

4. 228 Patients 5. Mean lesion length =

19 cm

DEB provisional Stent rate = 18.3%

Major Adverse Event

DEB DES p Adjusted p

N 131 97Any TLR 19.3% (21/109) 21.5% (21/79) 0.705 0.550

Clinical Driven TLR 15.6% (17/109) 19.0% (15/79) 0.543 0.572Loss of Patency 23.9% (26/109) 30.4% (24/79) 0.319 0.372

DEB IN COMPLEX SFA DISEASE

•FAIR TRIALDEB IN ISR

•DEBATE ISR TRIALDEB IN ISR (DIABETICS)

•DEFINITIVE-AR TRIALDEB FOLLOWING ATHERECTOMY

•PHOTOPAC TRIALDEB FOLLOWING LASER

ATHERECTOMY

•RIBS-VDEB VS. DES IN ISR

CONCLUSION:1. ROLE OF DEB IN SFA/POP INTERVENTION IS

PROMISING.2. DEB IS SUPEIOR TO PTA IN ALL CLINCAL

TRIALS.3. RESULTS OF DEB ANGIOPLASTY ARE

COMPARABLE OR BETTER THAN DES.4. DEB ARE EASIER TO USE. 5. IT IS COST EFFECTIVE MODALITY FOR DE-

NOVO AND RESTENOSIS LESIONS.6. COMPARE TO STENTS, NO ANATOMICAL

LIMITATION.7. DEB PRESERVE FUTURE PERCUTAEOUS AND

OPEN SURGERY OPTIONS.

THANK YOU!!!