Diabetic Patients Treated in the IMPERIAL Randomized Trial Comparing

Eluvia and Zilver PTX Stents Stefan Müller-Hülsbeck, MD

EBIR, FCIRSE, FICA, FSIRACADEMIC HOSPITALS Flensburg

Kiel University-Faculty of MedicineEv.-Luth. Diakonissenanstalt zu Flensburg

Tuesday, January 22, 2019

Disclosure

Speaker name: Stefan Müller-Hülsbeck

I have the following potential conflicts of interest to report:

Consulting

Employment in industry

Stockholder of a healthcare company

Owner of a healthcare company

Other(s)

Honoraria (Boston Scientific, Terumo, Eurocor Tech)

I do not have any potential conflict of interest

X

IMPERIAL Study Devices

Eluvia™ DES

Boston Scientific

Zilver® PTX®

Cook Medical

Stent Platform Innova Zilver Flex

Material Nitinol Nitinol

PolymerBiostable Fluorinated

Polymer Matrix (PROMUS polymer)

None

Drug

Dose DensityPaclitaxel

0.167 µg/mm2

Paclitaxel3 µg/mm2

Deployment Self-expanding Self-expanding

SizesDiameter Length Diameter Length

6-7 mm 40-150 mm 6-8 mm 40-120 mm

BSC Data on file. Cook Medical (2014). Zilver PTX Drug-Eluting Peripheral Stent Instructions for Use.

IMPERIAL Clinical Study Overview

• 180 patients had medically-treated diabetes (116 Eluvia & 64 Zilver PTX)

Primary Investigators

Global: William A. Gray, MD

European: Stefan Müller-Hülsbeck, MD

Study Design

RCT

(Eluvia DES vs Zilver PTX)

Long Lesion

Sub-study

(Eluvia)

Pharmacokinetic

Sub-study (Eluvia)

• 2:1 randomized

• Single-blind

• Non-inferiority trial

• Single arm

• Lesion length 140 mm-190 mm

• Single-arm

Patients

N=465

Eluvia N=309 vs

Zilver PTX N=156

N=50 N=13

InvestigationalCenters

65 study centers: US, Canada, New Zealand, Belgium, Germany, Austria, Japan

Key Eligibility Criteria

Inclusion

• Rutherford category 2, 3, or 4

• Lesions in the native

SFA and/or PPA

• Stenosis ≥70% by visual

angiographic assessment

• Vessel diameter 4-6 mm

• Total lesion length 30-140

mm

Exclusion

• Target lesion/vessel

previously treated with DCB

(<12 months prior) or

previously stented

• Prior surgery of the SFA/PPA

in the target limb

• Use of atherectomy, laser or

other debulking devices

• Dialysis

DCB, drug-coated balloon; SFA, superficial femoral artery; PPA, proximal popliteal artery

IMPERIAL Diabetic Cohort I Baseline CharacteristicsEluvia (N=116) Zilver PTX (N=64)

Patient CharacteristicsAge (y) 67.4±9.6 66.8±9.2Male 71.6% 73.4%Smoking History 89.7% 75.0%Hypertension 82.8% 90.6%Coronary Artery Disease 59.1% 57.8%Rutherford Classification

2 34.5% 26.6%3 62.1% 67.2%4 3.4% 6.3%

Lesion CharacteristicsLesion Length (mm) 87.0±38.1 84.5±38.3Reference Vessel Diameter (mm) 5.1±0.8 5.2±0.8

Calcification

None/Mild 32.2% 28.6%

Moderate 20.9% 30.2%

Severe 46.1% 39.7%

Unknown 0.9% 1.6%

% Diameter Stenosis 79.4±16.6 80.1±15.9

<50% 2.6% 0.0%

50%-99% 72.4% 73.0%

100% (Occlusion) 25.0% 27.0%

IMPERIAL Diabetic Cohort I Primary Patency at 12 Months

Primary patency defined as duplex ultrasound PSVR ≤2.4, in the absence of clinically-driven target lesion revascularization or bypass of the target lesion, as assessed by the DUS core lab.

Observed Rate: 84.6% (88/104) Eluvia vs 79.3% (46/58) Zilver PTX

Kaplan-Meier Estimate

log rank p=0.4413

Month

At risk: 6 9 12 13Eluvia 56 54 42 24.5Zilver PTX 28 24.5 17 8.5

Months Since Procedure

Pri

mar

y P

ate

ncy

Rat

e (

%)

0 1 2 3 4 5 6 7 8 9 10 11 12 13

0%

20%

40%

60%

80%

100%

80.2%

87.4%

Log-rank p= 0.2905

• 95.4% MAE-free at 12 months for patients treated with Eluvia

IMPERIAL Diabetic Cohort I Safety through 12 Months

Clinical Events Committee-adjudicated adverse events included all deaths, target limb major amputation, TLR, and stent thrombosis. Potential stent fractures were identified by radiography and verified by the angiographic core lab.

MAE, major adverse events; TLR, target lesion revascularization.

Eluvia (N=116)

Zilver PTX (N=64)

Difference[95% CI]

P-value

MAE 4.6% 13.6%-8.9%

[-18.5%, 0.7%]0.0658

All causes of death at 1 month 0.0% 0.0% 0.0% --

Target limb major amputation 0.9% 0.0%0.9%

[-0.9%, 2.7%]1.0000

Clinically-driven TLR 3.7% 13.6%-9.9%

[-19.3%, -0.4%]0.0269

Stent thrombosis 0.9% 8.1%-7.2%

[-14.2%, -0.1%]0.0235

0%

20%

40%

60%

80%

100%

Eluvia(N=115)

ZilverPTX

(N=63)

Eluvia(N=115)

ZilverPTX

(N=62)

Eluvia(N=110)

ZilverPTX

(N=58)

Eluvia(N=103)

ZilverPTX

(N=57)

Pe

rce

nta

ge o

f P

atie

nts

6

5

4

3

2

1

0

Best

Worst

IMPERIAL Diabetic Cohort I Clinical Outcomes through 12 Months

Eluvia Zilver PTX

Primary sustained clinical improvement

86.5% (90/104) 78.9% (45/57)

No or minimal symptoms (Rutherford Category 0-1)

83.7% (87/104) 82.5% (47/57)

Primary sustained clinical improvement: Improvement in Rutherford classification by one or more categories compared with baseline, without target lesion revascularization.

Baseline 1 Month 6 Months 12 Months

Rutherford Class Distribution

0%

20%

40%

60%

80%

100%

Baseline 1 Month 6 Months 12 Months

WIQ

Sco

re

Eluvia Distance Zilver PTX Distance

Eluvia Speed Zilver PTX Speed

Eluvia Stairs Zilver PTX Stairs

Eluvia Walking Impairment Zilver PTX Walking Impairment

Conclusions

• Excellent vessel patency and safety profile observed at 1 year in patients with diabetes treated with Eluvia

• Clinically-driven TLR and stent thrombosis occurred significantly more frequently among patients treated with Zilver PTX

• Data from this RCT subgroup as well as the IMPERIAL Long Lesion cohort suggest that the efficacy and safety profiles of Eluvia are not affected by challenging conditions

Status of dual layer stents for CAS:Is acute occlusion an issue?

No, neither in acute nor in elective cases...

... since you start an immeditate preparation with antiplateletmedication!

• Pre-procedural (elective treatment)

• Peri-procedural (stroke treatment) combinedwith bridging

500mg ASA i.v.

300mg Clopidogrel after control (conebeam-) CT, usually @ day 1

• Post-procedural

Diabetic Patients Treated in the IMPERIAL Randomized Trial Comparing

Eluvia and Zilver PTX Stents Stefan Müller-Hülsbeck, MD

EBIR, FCIRSE, FICA, FSIRACADEMIC HOSPITALS Flensburg

Kiel University-Faculty of MedicineEv.-Luth. Diakonissenanstalt zu Flensburg

Tuesday, January 22, 2019