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IN.PACT DEB TECHNOLOGY CLINICAL TRIAL OVERVIEW SFA RESULTS BTK RESULTS ORDER INFORMATION & ABBREVATIONS IN.PACT DEB Technology and Clinical Evidence IN.PACT DEB Technology Clinical Trial Overview SFA Results BtK Results Order information & Abbreviations

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Page 1: Medtronic In.Pact Clinical Evidence

IN.PACT DEB TECHNOLOGY

CLINICAL TRIAL OVERVIEW

SFA RESULTS

BTK RESULTS

ORDER INFORMATION

& ABBREVATIONS

IN.PACT DEB Technology andClinical Evidence

IN.P

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IN.P

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ORDER INFORMATION

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IN.PACT DEB Technology andClinical Evidence

BTK RESULTS

SFA RESULTS

CLINICAL TRIAL OVERVIEW

IN.PACT DEB TECHNOLOGY

4 DEB Components

FreePac Coating Technology

How to use a DEB

Page 3: Medtronic In.Pact Clinical Evidence

IN.PACT PACLITAXEL!ELUTING BALLOONS

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IN.PACT DEB TECHNOLOGY4 DEB components interweaving towards performance...

1. PLATFORMMEDTRONIC INVATEC

proven PTA full balloon line

PACLITAXELhydrophobic, lipophilic,

proven antiproliferative drug2. DRUG

UREAhydrophilic,

non toxic3. EXCIPIENT

MEDTRONIC INVATECuniformity + stability + release

controlled and scaleable4. COATING TECH

IN.PACT AmphirionPaclitaxel-Eluting PTA Balloon Catheter 0.014”

IN.PACT AdmiralPaclitaxel-Eluting PTA Balloon Catheter 0.035"

IN.PACT Paci!cPaclitaxel-Eluting PTA Balloon Catheter 0.018"

TECHNOLOGY

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BtK

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Global HeadquartersHungerbüelstrasse 128500 Frauenfeld – Switzerland

www.medtronic.comwww.invatec.com

IN.PACT PACLITAXEL!ELUTING BALLOONS

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FOLDS UNWRAPPINGThe balloon unwraps to

expose the FreePac coating

BALLOON INFLATED AND ELUTINGUrea molecules facilitate carriage of pacli taxel molecules across the

vessel wall

ELUTIONDrug elution takes place

within 30 - 60 seconds

DRUG UPTAKECOMPLETED

WRAPPED BALLOONThe IN.PACT DEB is

delivered to the target site

IN.PACT Paclitaxel elution timeline10 SECONDS 15 SECONDS 60 SECONDS

IN.PACT DEB TECHNOLOGY

TECHNOLOGY

IN.PACT™ DEB WITH FREEPAC™ COATING TECHNOLOGY

IN.PACT™Medtronic Invatec DEB balloon line

FREEPAC™Proprietary hydrophilic coating formulation– Urea separates Paclitaxel molecules– Increased drug solubility and optimal diffusion

into vessel wall– Urea facilitates Paclitaxel absorption into the vessel wall

PACLITAXEL - proven antiproliferative

UREA - natural and hydrophilic excipient

Page 5: Medtronic In.Pact Clinical Evidence

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Global HeadquartersHungerbüelstrasse 128500 Frauenfeld – Switzerland

www.medtronic.comwww.invatec.com

IN.PACT PACLITAXEL!ELUTING BALLOONS

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IN.PACT DEB TECHNOLOGY

FOLDED BALLOON

Handle with care

Lesion 2, DEB 2Lesion 1, DEB 1

2. Pre-dilatation

3. DEB

1. Lesion

Duration time 30 - 60 sec.

overlap overlap IF A STENT IS PRESENT AN OVERLAP WITH DEB IS RECOMMENDED

DRUG RELEASE WITHIN 30 ! 60 SECONDS• Longer inflation times are possible at

discre t ion of operator - to pursue optimal mechanical dilatation - but do not lead to further drug release

PRE!DILATATION RECOMMENDED IN CERTAIN CASES• For pre-dilatation in case of total occlusions

or sub-occlusive lesions use a standard balloon (approx. 0.5 mm smaller than RVD)

• Choose a DEB with a nominal size equal to reference diameter

ONE DRUG!ELUTING BALLOON FOR EACH LESION• For single use only, drug is released upon

the first inflation • In longer lesions DEB overlapping is indicated

HANDLE WITH CARE• DEB surface can be touched and handled gently• Do not rub the coated balloon• Do not use any protective / insertion sheath to

advance the DEB trough the introducer sheath and/or hemostatic valve

HOW TO USE DRUG ELUTING BALLOONS

TECHNOLOGY

Page 6: Medtronic In.Pact Clinical Evidence

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IN.PACT DEB TECHNOLOGY

IN.PACT DEB Technology andClinical Evidence

BTK RESULTS

SFA RESULTS

ORDER INFORMATION

& ABBREVATIONS

CLINICAL TRIAL OVERVIEW

IN.PACT Clinical Trial Program

Page 7: Medtronic In.Pact Clinical Evidence

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OVERVIEW

STATUS DATE: 01/2012

Indication Design # Sites ArmsPrimary Endpoint Pl(s) #Pts

SFAIN.PACT SFA I SFA de-novo RCT 10 DEB vs PTA +

prov Stent12m Prim. Patency

G. Tepe 150

IN.PACT SFA II SFA de-novo RCT 50 DEB vs PTA + prov Stent

12m Prim. Patency

P. Schneider, J. Laird

280

DEB SFA IT Registry* SFA de-novo Registry 6 DEB + prov Stent

6m Patency A. Micari 105

PACIFIER* SFA de-novo RCT 3 DEB vs PTA + prov Stent

6m LLL M. Werk 91

ISAR-STATH* SFA de-novo RCT 2 DEB + Stent vs Stent vs Ather.

6m %DS I. Ott, M. Fusaro

150

IN.PACT CALCIUM* SFA de-novo Ca++

Registry 1 Atherectomy + DEB

12m RR (DUS) A. Cioppa 20

SFA-ISRPHOTOPAC* SFA ISR RCT 3 Laser + DEB vs

DEB alone12m %DS T. Zeller 50

FAIR* SFA ISR RCT 3 DEB vs PTA 6m DUS re-restenosis

H. Kranken-berg

118

ISAR PEBIS* SFA ISR RCT 1 DEB vs PTA 6m %DS I. Ott, M. Fusaro

70

FRENCH SFA Registry* SFA ISR Registry 13 DEB 12m TLR Y. Gouë!c 100

SFA & BTKDEBELLUM* SFA BTK RCT 1 DEB vs PTA 6m LLL F. Fanelli 50

BTKDEB BTK IT Registry* BTK de-novo Registry 6 DEB + prov

Stent6m RR (Angio) G. Biamino 100

IN.PACT BTK Abano* BTK de-novo Registry 1 DEB + prov Stent

6m RR (Angio) M. Manzi 122

IN.PACT BTK DEB Leipzig Registry*

BTK de-novo Registry 1 DEB + prov Stent

3m RR (Angio) D. Scheinert 107

IN.PACT DEEP BTK / CLI de-novo

RCT 11 DEB vs PTA + prov Stent

12m LLL + TLR + 6m Events

I. Baumgart-ner, T. Zeller, D. Scheinert

357

DEBATE* BTK/CLI/ Diabetics

RCT 1 DEB vs PTA + prov Stent

12m Angio RR F. Liistro 150

16 Clinical Trials / 10 RCT / 113 Clinical Sites / 2.020 patients

IN.PACT CLINICAL TRIAL PROGRAM

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* Physician sponsored

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IN.PACT DEB TECHNOLOGY

ORDER INFORMATION

& ABBREVATIONS

IN.PACT DEB Technology andClinical Evidence

BTK RESULTS

CLINICAL TRIAL OVERVIEW

SFA RESULTS

Italian SFA Registry

SFA Trial PACIFIER

SFA Trial DEBELLUM

Page 9: Medtronic In.Pact Clinical Evidence

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IN.PACT AdmiralPACLITAXEL!ELUTING PTA BALLOON CATHETER 0.035"

IN.PACT drug-eluting balloon demonstrates high primary patency with low stent rateData presented at PCR 2011 by Dr. Micari

REGISTRY PURPOSETo assess the benefit of DEB usage within standard practice for the treatment of femoro-popliteal arterial disease in patients with claudication and rest pain

PRIMARY ENDPOINT The primary endpoint was primary patency at 12 months

STUDY METHODS- Investigator sponsored multi-center observational registry- Predilatation with conventional undersized PTA balloon, DEB dilatation for 180 sec- Provisional stenting in case of flow limiting dissections and persistent residual

stenosis > 50%

PATIENT DEMOGRAPHICS

DEB SFA ITALIAN REGISTRY

* Micari et al., EuroIntervention Volume 7, Supplement K, May 2011, A new paclitaxel-eluting balloon for angioplasty of femoro-popliteal obstructions: acute and midterm results

HypertensionHyperlipidaemia

DiabetesInsul. dependant

Renal insufficiencySmoking

Coronary Artery Dis.Carotid Artery Dis.

!105 PATIENTS, AGE 68 ± 9"

Average Lesion Length: 76mm. Total Occlusions: 29.8%. ABI 0.56 ± 0.15Rutherford Class II 26,7%, Rutherford Class III 64,8%, Rutherford Class IV 7.6%

DEB SFA ITALIAN REGISTRY*

DRUG#ELUTING BALLOONS FOR LOWER LIMB ARTERIAL DISEASE

10 20 30 40 50 60 70 80 90 100

90 (85.7%)78 (74.3%)

51 (48.6%)23 (45.1%)

2 (1.9%)66 (62,8%)

45 (42.9%)15 (14.3%)

STATUS DATE: 02/2012

SFADE!NOVO

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IN.PACT AdmiralPACLITAXEL!ELUTING PTA BALLOON CATHETER 0.035”

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Global HeadquartersHungerbüelstrasse 128500 Frauenfeld – Switzerland

www.medtronic.comwww.invatec.com

REGISTRY CONCLUSION & DISCUSSION

12 MONTHS RESULTS

– High primary patency rate and low TLR rate despite conservative usage of stents– Clinical benefit is consistently shown across multiple endpoints Patency rates are in line with previously reported results of Drug Eluting Balloons (Thunder, Fempac)**

– Primary Patency 83.7%– TLR rate 8.7%– ABI, Quality of Live,

Walking capacity, Rutherford class improvements

DEB SFA ITALIAN REGISTRY IN.PACT drug-eluting balloon demonstrates high primary patency with low stent rate

ACUTE OUTCOME

Device Success · · · · · · · · · · · · · · · · · · · · · · 135 (100%)

Stenting · · · · · · · · · · · · · · · · · · · · · · 14 (12.3%)

Tech. Success · · · · · · · · · · · · · · · · · · · · · · 121 (89.6%)

Pre-dilatation · · · · · · · · · · · · · · · · · · · · · · 113 (99.1%)

DEB inflation time · · · · · · · · · · · · · · · · · · · · · · 181 ± 20.4 sec

No DEB p/lesion · · · · · · · · · · · · · · · · · · · · · · 135/114 = 1.18

** Tepe et al., N Engl J Med 2008; 358:2406-2407 / Werk et al., Circulation. 2008; 118: 1358-1365

0 180 360

100%90%80%70%60%50%40%30%20%10%

12M Survival from TLR, Occlusion, >50% Restenosis Primary Patency 83.7%

days after procedure

PSVR <2.5

STATUS DATE: 02/2012

SFADE!NOVO

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IN.PACT PacificPACLITAXEL!ELUTING PTA BALLOON CATHETER 0.018"

IN.PACT drug eluting balloon superior to PTA with regards to 6 months Late Lumen LossData presented at LINC 2012 by Dr. Werk

STUDY PURPOSETo demonstrate efficacy of the paclitaxel eluting balloon to inhibit restenosis of femoropopliteal stenosis and occlusions vs. standard PTA

PRIMARY AND SECONDARY ENDPOINTS - The primary endpoint was Late Lumen Loss (LLL) at 6 months- Secondary endpoints: 6-m binary restenosis rate, 6-m TLR, 6-m RC change,

6-m event free survival

STUDY METHODS- Investigator sponsored multi-center randomized (1:1) trial- Independent, blinded Angiographic Corelab- Provisional stenting in case of flow limiting dissection or persistent residual stenosis

PATIENT DEMOGRAPHICS AND LESION CHARACTERISTICS

THE PACIFIER TRIAL

* A Randomized Multicenter Trial Evaluating Prevention of Restenosis with Paclitaxel-Coated PTA Balloon Catheters in Stenosis or Occlusion of Femoropopliteal Arteries

M. Werk, T. Albrecht, D.-R. Meyer, H. Stiepani, B. Schnorr, U. Dietz, E. Lopez Hänninen

Departments of Radiology of the Martin-Luther-Hospital, Hubertus-Hospital, Vivantes Klinikum Neukölln, Berlin, Germany

presented at LINC 2012

SFA TRIAL " PACIFIERDRUG!ELUTING BALLOONS FOR LOWER LIMB ARTERIAL DISEASE

DEB Control

No. of Patients n 44 47Mean Age y ± SD 71 ± 7 71 ± 9

Diabetes n (%) 19 (43%) 13 (28%)Hypertension n (%) 29 (66%) 31 (66%)

Hypercholesterolemia n (%) 22 (50%) 22 (47%)ABI mean ± SD 0.73 ± 0.30 0.65 ± 0.26

95% of patients were in Rutherford classes 2 or 3 at baseline.

Avg lesion length cm ± SD 7.0 ± 5.3 6.6 ± 5.5Ref. Vessel Diameter mm 4.92 4.90 % Diameter Stenosis (%) 73% 80%

Total Occlusions n (%) 10 (23%) 18 (38%)

68% (DEB arm) were de-novo lesions, but also restenotic and ISR was included in the protocol.

SFADE!NOVO

STATUS DATE: 02/2012

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IN.PACT PacificPACLITAXEL!ELUTING PTA BALLOON CATHETER 0.018”

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Global HeadquartersHungerbüelstrasse 128500 Frauenfeld – Switzerland

www.medtronic.comwww.invatec.com

CONCLUSION

6 MONTHS RESULTS !ANGIOGRAPHIC AND CLINICAL"

IN.PACT PACIFIC™ confirms to effectively reduce neointima hyperplasia in SFA with a significant decrease in LLL at 6 months vs standard PTA Clinical Events (Secondary Endpoints) trend / are in favor of DEBNo coating related adverse events noted

SFA TRIAL " PACIFIER IN.PACT drug eluting balloon superior to PTA with regards to 6 months Late Lumen Loss

ACUTE OUTCOME

DEB Control P valuePre-Dilatation n (%) 6 (13.6%) 3 (6.4%) 0.30

Balloon inflation time mean ± SD 76 ± 33 sec 76 ± 25 sec 0.89Dissections n (%) 18 (41%) 25 (53%) 0.48

Provisional Stent Rate n (%) 9 (21%) 16 (34%) 0.17Residual Stenosis mean±SD 12±12% 11±12% 0.5

DEB Control P value% Diameter Stenosis % 29.7% 39.4% 0.05

Min. Lumen Diameter mm 3.61 2.94 0.0014Binary Restenosis n/N (%) 3/35 (8.6%) 11/34 (32.4%) 0.01

Late Lumen Loss mm -0.01 0.65 0.0014

30% –

25% –

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0% –

TLR Amputation Death Composite

6M MAJOR ADVERSE EVENTS

DEB

Control

SFADE!NOVO

7.1% 7.1%

21.4%

p=0.12

p=0.04

26.2%

0.0% 0.0% 0.0%

4.8%

STATUS DATE: 02/2012

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IN.PACT drug eluting balloon superior to PTA with regards to 6 months Late Lumen LossData presented at MEET 2011 by Dr. F. Fanelli

STUDY PURPOSETo assess the effect of DEB for multilevel lower limb revascularization compared to PTA

PRIMARY AND SECONDARY ENDPOINTS - The primary endpoint was Late Lumen Loss (LLL) at 6 months (US evaluation)- Secondary endpoints: Target Lesion Revascularization, Thrombosis and Amputation

STUDY METHODS– Investigator sponsored single-center randomized (1:1) trial– Provisional Stenting in case of flow limiting dissection or persistent residual stenosis– Study devices: IN.PACT Amphirion (BtK) and IN.PACT Admiral (SFA)

STUDY DESIGN

PATIENT DEMOGRAPHICS AND LESION CHARACTERISTICS

DEBELLUM

* Dr. Fabrizio Fanelli Vascular and Interventional Radiology Unit Department of Radiological Sciences “Sapienza” - University of Rome

presented at MEET 2011

DEBELLUM: Drug Eluting Balloon Evaluation for Lower Limb mUltilevel treatMent*

DRUG!ELUTING BALLOONS FOR LOWER LIMB ARTERIAL DISEASE

Patient Demographics

Patients n 50Age y 67 ± 21

Diabetes 22 (45%)High Cholesterol 29 (59%)

Hypertension 34 (68%)ABI 0.53 ± 0.18

Fontaine Stage 2b 31 (62%)Fontaine Stage 3 14 (28%)Fontaine Stage 4 5 (10%)

Lesion Characteristics

Overall Lesions 122Femoro-Popliteal Lesions 92 (76%)

BtK Lesions 30 (24%)Mean Lesion Length (cm) 7.5 ± 3.5

% Stenosis Diameter 85 ± 6.4

Total Occlusion 26 (22%)

N= 50 PTS. PRIMARY ENDPOINT: LATE LUMEN LOSS AT 6 MONTHS

N= 25 pts | 57 lesions

Native Stenosis (26 lesions)

Stenting (31 lesions)

Native Stenosis (30 lesions)

Stenting (35 lesions)

N= 25 PTS | 65 LESIONSDEB

Uncoated balloons

STATUS DATE: 02/2012

SFA/BTK

IN.PACT AdmiralPACLITAXEL!ELUTING PTA BALLOON CATHETER 0.035"

IN.PACT AmphirionPACLITAXEL!ELUTING PTA BALLOON CATHETER 0.014"

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Global HeadquartersHungerbüelstrasse 128500 Frauenfeld – Switzerland

www.medtronic.comwww.invatec.com

CONCLUSION

6 MONTHS SUBANALYSIS

Drug eluting balloons are safe and effective for the inhibition of neointimal hyperplasiaNo significative different results between native stenosis and post-stents dilatationSix-months follow-up showed lower neointimal hyperplasia, lower TLR rates and better clinical outcomes in the DEB group compared with the non-coated balloon group.*

DEBELLUM: Drug Eluting Balloon

Evaluation for Lower Limb mUltilevel treatMent

IN.PACT drug eluting balloon superior to PTA with regards to 6 months Late Lumen Loss

6 MONTHS RESULTS !ANGIOGRAPHIC AND CLINICAL"

SECONDARY ENDPOINTSTLR clinically and diagnostic (USCD or DSA) driven

Overall analysis: 0.5±1.4mm (DEB) vs 1.6±1.7mm (PTA). P<0.01Native stenosis analysis: 0.5mm (DEB) vs 1.5mm (PTA. P<0.01Stent analysis: 0.51mm (DEB) vs 1.7mm (PTA). P<0.01

DEB

PTA

STATUS DATE: 02/2012

* the study was not powered against secondary endpoints.

DRUG!ELUTING BALLOONS FOR LOWER LIMB ARTERIAL DISEASE

SFA/BTK

2.0 mm –

1.5 mm –

1.0 mm –

0.5 mm –

0 mm –Overall values Native Stenosis

AnalysisStent Analysis

0.5 0.5 0.51

1.6 1.51.7

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IN.PACT AdmiralPACLITAXEL!ELUTING PTA BALLOON CATHETER 0.035"

IN.PACT AmphirionPACLITAXEL!ELUTING PTA BALLOON CATHETER 0.014"

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IN.PACT DEB Technology andClinical Evidence

ORDER INFORMATION

& ABBREVATIONS

IN.PACT DEB TECHNOLOGY

SFA RESULTS

CLINICAL TRIAL OVERVIEW

BTK RESULTS

BtK DEB Leipzig Registry

DEBATE-BtK

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IN.PACT AmphirionPACLITAXEL!ELUTING PTA BALLOON CATHETER 0.014"

BTK DEB LEIPZIG REGISTRYIN.PACT drug eluting balloon reduces early restenosis and TLR Rate of long BtK lesions

REGISTRY PURPOSEThe purpose of this study was to investigate the efficacy of drug-eluting balloons (DEBs) in the treatment of long infrapopliteal lesions with regard to the short-term restenosis rate and midterm clinical result.

PRIMARY ENDPOINT The primary endpoint was the angiographic binary restenosis.

STUDY METHODSInfrapopliteal angioplasty was performed with an IN.PACT AMPHIRION paclitaxel-eluting balloon clinical and angiographic follow-up was performed at 3 months to detect bina-ry restenosis, and further clinical assessment was performed over a 12-month period.

BTK REGISTRY

* Schmidt et al. J Am Coll Cardiol.2011; 58: 1105-1109

** Schmidt et al. Catheterization and Cardiovas-cular Interventions, 76:!1047–1054

A. Schmidt, MD Center of Vascular Medicine Angiolo-gy, Cardiology and Vascular Surgery Park Hospital Leipzig, Germany

10 20 30 40 50 60 70 80 90 100

PATIENT DEMOGRAPHICS (104 Patients, Age 73.6 ± 6.7, Male 69 =66.3%)

Arterial hypertensionDiabetes mellitus

Smoking habitHypercholesterolemia

Obesity Coronary artery disease

NYHA functional classes III and IV Renal insufficiency (GFR 60 ml/min/1.73 m2)

Cerebrovascular disease

95 (91.3%)74 (71.1%)

32 (30.8%)68 (65.4%)

33 (31.7%)47 (45.9%)

23 (22.1%)48 (46.2%)

19 (18.3%)

STATUS DATE: 01/2012

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Global HeadquartersHungerbüelstrasse 128500 Frauenfeld – Switzerland

www.medtronic.comwww.invatec.com

IN.PACT AmphirionPACLITAXEL!ELUTING PTA BALLOON CATHETER 0.014”

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REGISTRY CONCLUSION & DISCUSSIONThe early restenosis rate of long-segment infrapopliteal disease is significantly lower after treatment with DEBs compared with historical data using uncoated balloons.

A historical control group** with similar patients showed 69% binary restenosis rate at 3 months, 56% restenosis of the whole segment and a TLR rate of 50% at 15 months. DEB resulted in better restenosis rate at 3 months, lower rate of totally occluded arte-ries and lower TLR rates.

BTK DEB LEIPZIG REGISTRY IN.PACT drug eluting balloon reduces early restenosis and TLR Rate of long BtK lesions

CLINICAL RESULTS

RUTHERFORD SHIFT !12.5 MONTHS"

TLR at 12 months · · · · · · · · · · · · · · · · · · · · · · · · · 17.4%

Rate of completely occluded arteries · · · · · · · · · · · · · · · · · · · · · · · · · 9.5%

Binary restenosis rate at 3 months · · · · · · · · · · · · · · · · · · · · · · · · · 27.4%

Clinical improvement · · · · · · · · · · · · · · · · · · · · · · · · · 95.6%

Complete wound healing · · · · · · · · · · · · · · · · · · · · · · · · · 74.2%

Favourable clinical results and a limb salvage rate of 95.4%

70605040302010

0 0 1 2 3 4 5 6

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19 (1

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19 (1

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ANGIOGRAPHIC RESULTSMean infrapopliteal lesion length was 17.6mm. Angiography at 3 months found 72.6% of all arteries free of significant restenosis.

1 (9.1%)

5 (9.3%)9 (20.0%)

7 (18.9%)5 (38.5%)

15 (31.3%)3 (16.7%)

3 (16.7%)5 (31.3%)

Distal poplitealAnterior tibial arteryTibioperone al trunk

Posterior tibial arteryPeronal artery

Proximal segment of tibial arteriesMid segment of tibial arteries

Distal segment of tibial arteriesArteries distal to the malleolus

5 10 15 20 25 30 35 40

3 MONTHS ANGIOGRAPHIC RESTENOSIS RATE BY VESSEL DISTRICT !104 PATIENTS, AGE 73.6 ± 6.7"

STATUS DATE: 01/2012

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CLINICAL RESEARCH Interventional Cardiology

First Experience With Drug-Eluting Balloonsin Infrapopliteal ArteriesRestenosis Rate and Clinical Outcome

Andrej Schmidt, MD,* Michael Piorkowski, MD,* Martin Werner, MD,* Matthias Ulrich, MD,*Yvonne Bausback, MD,* Sven Bräunlich, MD,* Henrik Ick, MD,* Johannes Schuster, MD,*Spiridon Botsios, MD,* Hans-Joachim Kruse, MD,† Ramon L. Varcoe, MD,‡ Dierk Scheinert, MD*

Leipzig and Zschopau, Germany; and Sydney, Australia

Objectives The purpose of this study was to investigate the efficacy of drug-eluting balloons (DEBs) in the treatment of longinfrapopliteal lesions with regard to the short-term restenosis rate and midterm clinical result.

Background Restenosis rates of long-segment tibial artery disease are very high. Recently, a restenosis rate of 69% at3 months after standard balloon angioplasty was demonstrated.

Methods Infrapopliteal angioplasty was performed with a paclitaxel-eluting balloon (In.Pact Amphirion, Medtronic, Minne-apolis, Minnesota). Clinical and angiographic follow-up was performed at 3 months to detect binary restenosis,and further clinical assessment was performed over a 12-month period thereafter.

Results In 104 patients, 109 limbs were treated for critical limb ischemia (82.6%) or severe claudication (17.4%). Meanlesion length of the arteries treated was 176 ! 88 mm. Angiography studied in 84 treated arteries at 3 monthsshowed a restenosis in 27.4% (19.1% had restenosis of more than 50%, and 8.3% were totally occluded) andusually occurred focally. Only in 9.5% of all angiographically followed up arteries was the entire treated segmentrestenosed or reoccluded. During a follow-up period of 378 ! 65 days, 1 patient was lost and 17 died. Of the91 limbs remaining in the analysis, clinical improvement was present in 83 (91.2%). Complete wound healingoccurred in 74.2%, whereas major amputation occurred in 4 patients, resulting in limb salvage of 95.6% for pa-tients with critical limb ischemia.

Conclusions The early restenosis rate of long-segment infrapopliteal disease is significantly lower after treatment with DEBscompared with historical data using uncoated balloons. Randomized trials are required to show whether thisdifference will lead to improvement in clinical outcomes. (J Am Coll Cardiol 2011;58:1105–9) © 2011 by theAmerican College of Cardiology Foundation

Percutaneous transluminal angioplasty (PTA) is increas-ingly used to treat infrapopliteal arterial disease. However,the high restenosis rate is problematic, and repeat interven-tions may be required in a significant proportion of patientsto achieve clinical goals (1,2). Drug-eluting stents have beendemonstrated to be effective in lowering the restenosis ratebelow the knee (BTK) (3). Their design for coronaryarteries makes them a practical option more suited toshorter tibial lesions. For long-segment BTK disease, drug-eluting balloons (DEBs) have been designed to reduce the

restenosis rate. Initially emerging as a new treatment optionfor coronary arteries (4), they also have been studied in thefemoropopliteal segment (5,6). In our registry, we aimed toinvestigate a recently approved DEB for its application ininfrapopliteal arteries.

See page 1110

Methods

Patient selection and interventional technique. Con-secutive patients with critical limb ischemia (CLI) or severeclaudication and BTK lesions (stenosis: !70% or occlu-sions) with a lesion length of 80 mm or more were treatedwith a paclitaxel-eluting balloon (In.Pact Amphirion,Medtronic, Minneapolis, Minnesota). The balloon is coatedwith FreePac, a proprietary formulation of 3.0 "g paclitaxel/mm2 and urea, which serves as a hydrophilic spacer to

From the *Center of Vascular Medicine, Angiology and Vascular Surgery, ParkHospital Leipzig, Leipzig, Germany; †Outpatient Facility for Vascular DiseasesZschopau, Zschopau, Germany; and the ‡Department of Surgery, Prince of WalesHospital and University of New South Wales, Sydney, Australia. Drs. Schmidt andScheinert are consultants for Medtronic. All other authors have reported that theyhave no relationships relevant to the contents of this paper to disclose.

Manuscript received February 14, 2011; revised manuscript received May 17, 2011,accepted May 24, 2011.

Journal of the American College of Cardiology Vol. 58, No. 11, 2011© 2011 by the American College of Cardiology Foundation ISSN 0735-1097/$36.00Published by Elsevier Inc. doi:10.1016/j.jacc.2011.05.034

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facilitate separation and releaseof paclitaxel into the vessel wall.Pre-dilation with an uncoatedballoon was performed to ensurean uncomplicated insertion ofthe DEB into the lesions. TheDEB diameter was 0.5 mmlarger than the uncoated balloonto guarantee contact of the DEBto the arterial wall. DEBs had adiameter of 2.0 to 4.0 mm and alength of 80 to 120 mm. If more

than 1 balloon was used per lesion, overlap of the DEBs was5 mm. Inflation time was at least 1 min. In case offlow-limiting dissection or residual stenosis of more than30%, a prolonged dilation of up to 5 min was performed.Stents were used as bailout for unsatisfactory results. Successwas defined as at least 1 infrapopliteal artery restoration incontinuity to the foot with a residual stenosis of less than30%. Inflow lesions were treated during the same session.Pharmacologic therapy. All patients were taking aspirin100 mg daily. After sheath insertion, 5,000 IU heparin wasadministered. After angioplasty, intra-arterial nitroglycerin200 to 300 !g was administered routinely to resolvevasospasm. Post-intervention dual antiplatelet therapy withaspirin 100 mg and clopidogrel 75 mg once daily was givenat least for 4 weeks and 100 mg aspirin was given dailythereafter.Endpoints. The primary endpoint was the angiographicbinary restenosis. Angiographic follow-up was scheduled 3months after the initial procedure according to our hospitalstandards. Selective angiographies in 2 different projectionswere evaluated by 2 investigators based on visual estimate.Binary restenosis was calculated using a 50% diameterreduction threshold. Clinical outcome was assessed at 3 and12 months after angioplasty. Clinical improvement wasdefined as marked ("50%) reduction of ulcer size or depthor increase of at least 1 Rutherford-Becker category. Am-putations and the necessity for target lesion revasculariza-tion (TLR) or bypass surgery were recorded. This study wasperformed without industry financial support. Data analysiswas performed retrospectively. The registry adhered to therequirements of the local ethics committee, and all patientsgave their written informed consent before the procedure.Statistical analysis. Continuous data are given as mean !SD. Categorical variables are expressed as numbers andpercentage.

Results

Baseline characteristics of patients and lesions. BetweenJanuary 2009 and February 2010, 104 consecutive patientsmeeting the inclusion criteria were studied. In these pa-tients, 109 limbs were treated either for CLI (82.6%) orsevere claudication (17.4%). Patient characteristics are givenin Table 1.

Before treatment, 77.1% of the patients had complete orfunctional occlusion of all 3 infrapopliteal arteries. Meaninfrapopliteal lesion length was 176 ! 88 mm. The numberof arteries treated was left to the discretion of the interven-tionalist; however, in only 5 limbs was more than 1 arterytreated.

The mean number of DEBs used per artery was 1.9(range: 1 to 5). In 28 limbs, a proximal angioplasty (allinfrainguinal) was performed additionally during the sameintervention using uncoated balloons.Peri-procedural outcomes. Interventional success wasachieved in all limbs, and stenting was necessary in 5 cases.Inevitable toe amputation was performed in 3 patients in theperi-interventional period. Complications before dischargeincluded 3 femoral pseudoaneurysms, only 1 requiringsurgical repair. One patient with an infected diabetic footwho was Rutherford-Becker category 6 died as a result of amajor amputation performed 21 days after PTA.3-month follow-up. During this period, 8 additional pa-tients died, 7 of cardiac disease and 1 of a bronchial cancerdiagnosed before PTA. One patient was lost for follow-up.Clinical improvement in the remaining 94 patients was seenin 75.8% of the treated limbs, 22.2% were unchanged, and2.0% were clinically worse. Three additional toe amputa-tions were performed. Complete wound healing was notedin 41.9% of the Rutherford-Becker category 5 limbs.Twenty patients declined to undergo repeat angiography.There was no difference in lesion characteristics or 3-monthclinical outcomes between the patients with or withoutrepeat angiography.Subgroup of angiographically examined patients at3 months. Angiography at 3 months was performed in 74patients with 79 treated limbs and 84 arteries treated withDEBs. Lesion characteristics are given in Table 2. BeforePTA, target arteries were stenosed in 38.1% and wereoccluded in 61.9%. Angioplasty was performed for 55 de

Demographic Patient DataTable 1 Demographic Patient Data

Age (yrs) 73.6 ! 6.7

Male 69 (66.3%)

Arterial hypertension 95 (91.3%)

Diabetes mellitus 74 (71.1%)

Smoking habit 32 (30.8%)

Hypercholesterolemia 68 (65.4%)

Obesity 33 (31.7%)

Coronary artery disease 47 (45.9%)

NYHA functional classes III and IV 23 (22.1%)

Renal insufficiency (GFR "60 ml/min/1.73 m2) 48 (46.2%)

Cerebrovascular disease 19 (18.3%)

Rutherford-Becker category 6 1 (0.9%)

Rutherford-Becker category 5 70 (64.2%)

Rutherford-Becker category 4 19 (17.45%)

Rutherford-Becker category 3 19 (17.45%)

Values are mean ! SD or n (%).GFR # glomerular filtration rate calculated by MDRD formula (Modification of Diet in Renal

Disease); NYHA # New York Heart Association.

Abbreviationsand Acronyms

BTK ! below the knee

CLI ! critical limbischemia

DEB ! drug-eluting balloon

PTA ! percutaneoustransluminal angioplasty

TLR ! target lesionrevascularization

1106 Schmidt et al. JACC Vol. 58, No. 11, 2011Drug-Eluting Balloons for Tibial Arteries September 6, 2011:1105–9

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novo lesions, 19 restenoses, and 10 in-stent restenoses.Mean lesion length was 173 ! 87 mm and mean DEBdiameter was 2.72 ! 0.41 mm. Bailout stenting wasperformed in 5 cases. Cypher stents (Cordis, Miami, Flor-ida) were used in 3 cases, and self-expanding nitinol stents(Maris Deep, Medtronic) were used in 2 cases. Full lesioncoverage was performed in 1 of the cases.

Angiography at 3 months (mean 98 ! 22 days) found 61(72.6%) of 84 arteries free of significant restenosis. In27.4%, a restenosis of more than 50% was found (19.1% hada restenosis and 8.3% were occluded). In most of thesecases (61%), restenosis developed only focally ("20% ofthe length of the initial target lesion) (Fig. 1). Restenosisor reocclusion of the entire target lesion occurred only in8 (9.5%) of the 84 treated arteries. Higher restenosis rateswere seen after treatment of distal segments, especiallywhen foot arteries were involved (Table 2). Two (2.4%)of the 84 treated arteries became ectatic within thetreated segment (less than double of the reference vesseldiameter), and 1 was associated with restenosis. Clinicalimprovement in limbs with restenosis was similar to thatof those without.Midterm clinical follow-up. After a mean follow-up of378 ! 65 days, 86 patients with 91 treated limbs wereevaluated clinically. Clinical improvement occurred in91.2% of these limbs. No bypass surgery was performedduring the entire study period. TLR was performed in17.3%. Limb salvage was achieved in 95.6% of the CLIpatients and complete wound healing occurred in 74.2% ofthe patients with Rutherford-Becker category 5 at baseline.Eight additional patients died, all for unrelated reasons,resulting in a mortality rate of 16.3% at 1 year. There were4 unplanned amputations during this period, 1 single toeamputation, 1 forefoot amputation, and 2 major BTKamputations. The Rutherford-Becker categories of all pa-tients before and after 1 year are shown in Figure 2.

Discussion

The restenosis rate after PTA of infrapopliteal arteries isvery high. In a series recently published treating infrapop-

Location of Angioplasty of Patients Who Underwent3-Month Angiography and Restenosis Rate inRelation to the Treated Artery and Site of theTreated Segment

Table 2

Location of Angioplasty of Patients Who Underwent3-Month Angiography and Restenosis Rate inRelation to the Treated Artery and Site of theTreated Segment

Artery or Site Involved in PTA n (%) Restenosis (%)

Distal popliteal artery 11 (13.1) 1 (9.1)

Anterior tibial artery 48 (57.1) 15 (31.3)

Tibioperoneal trunk 18 (21.4) 3 (16.7)

Posterior tibial artery 16 (19.0) 5 (31.3)

Peroneal artery 18 (21.4) 3 (16.7)

Proximal segment of tibial arteries 54 (64.3) 5 (9.3)

Mid segment of tibial arteries 45 (53.6) 9 (20.0)

Distal segment of tibial arteries 37 (44.0) 7 (18.9)

Arteries distal to the malleolus 13 (15.5) 5 (38.5)

PTA # percutaneous transluminal angioplasty.

Figure 1 Focal Restenosis at 3 Months

(A) Angiographic image showing total occlusion of the anterior tibial artery leftleg (dashed line and arrows). (B) Angiographic image obtained after angio-plasty of the anterior tibial artery with drug-eluting balloons. (C) Angiographicimage obtained after 3 months showing a focal restenosis (arrow).

1107JACC Vol. 58, No. 11, 2011 Schmidt et al.September 6, 2011:1105–9 Drug-Eluting Balloons for Tibial Arteries

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liteal arteries with a mean lesion length of 183 mm withuncoated low-profile balloons, we demonstrated an angio-graphic restenosis rate of 69% at 3 months (2). Because ofthis finding, we selected long BTK lesions for treatmentwith the recently approved infrapopliteal DEB (In.PactAmphirion). The mean lesion length of 173 mm in thisseries is comparable in length with that of our previous study(2). The 3-month restenosis rate of 27% after treatmentwith DEB represents a dramatic reduction for restenosis of61% from the 69% seen in the series using uncoatedballoons (2). In addition, we observed an altered pattern ofrecurrent disease that favored the DEB. Whereas restenosisusually involved the whole treated segment with uncoatedballoons (2), restenosis after DEB was found to be focal,involving !20% of the length of the target lesion in morethan 60% of the restenosed vessels. This pattern of shorterrestenosis may have less impact on flow compared with thediffuse type and also simplifies TLR.

Although our series is too small to perform a meaningfulsubanalysis of factors that may influence patency after PTAwith DEBs, the most distal lesions seem to perform worst. ForDEB angioplasty distal to the malleolus, we found a restenosisrate of 38.5% at 3 months. This is consistent with otherpublished series that recognize standard balloon angioplasty forpedal arteries to be a predictor of limb loss (1). The highrestenosis rate we observed in this region may be a contributingfactor.Safety of DEBs in BTK arteries. We found nothing toindicate the use of DEBs BTK to be unsafe. An amputationrate of 4.4% is very acceptable for CLI patients. During the3-month angiogram, 2 arteries became moderately ectaticwithin the treated segment, which resulted in no adverseclinical events. This has not been described previously forDEBs for other arteries. We do not believe that thisobservation raises concerns regarding the safety of DEBs inthe infrapopliteal circulation.

Clinical results. Multiple factors contribute to wound heal-ing and limb salvage, including local wound care and surveil-lance regimen, which may be equally as important as revascu-larization. It therefore may be difficult to prove the superiorityof the DEBs over uncoated balloons for these clinical end-points. In fact, similar favorable results for wound healing andlimb salvage have been described after plain old balloonangioplasty of long infrapopliteal disease (2,7). TLRs fre-quently are needed after endovascular treatment of BTKarteries (1,2) and therefore may be considered a more usefulclinical endpoint. Compared with the TLR rate of 50% in ourseries using uncoated balloons (2), the use of DEBs resulted ina TLR rate of 17.3%, a considerable reduction of 65.4%. It iswith regard to TLR that the use of DEBs has most potentialto improve clinical outcomes compared with standard balloons.Costs are likely to play an important role for the use of DEB;however, the potential reduction in number of reinterventionsalso must be considered in these calculations if we are tocompare DEBs with uncoated balloons.Study limitations. Quantitative angiography to determinedegree of restenosis in long BTK lesions is technically verychallenging. In practice, however, the visual assessment ofangiography was believed to be significantly more precisethan the alternatives of duplex ultrasound, magnetic reso-nance angiography, or computed tomography angiography.Only 1 DEB, the In.Pact Amphirion, was approved forperipheral artery application in Europe and therefore wasthe only one used during the study period. Other DEBs maylead to differing results in the future.

Conclusions

This first report of the use of DEBs BTK suggests that they aresafe and effective in this arterial region. When compared witha series using uncoated balloons, the data presented heredemonstrate a marked, more than 60% reduction in therestenosis rate at 3 months. In addition, if restenosis occurred,it was associated with a favorable, focal pattern. The 1-yearclinical results are promising and seem to confer a durablebenefit. Further evidence, in the form of randomized con-trolled trials, is required to confirm whether DEBs are superiorto the standard treatment of plain old balloon angioplasty inpatients with CLI from BTK disease.

Reprints requests and correspondence: Dr. Andrej Schmidt,Center of Vascular Medicine, Angiology and Vascular Surgery,Parkkrankenhaus Leipzig, Strümpellstrasse 41, 04289 Leipzig,Germany. E-mail: [email protected].

REFERENCES

1. Fernandez N, McEnaney R, Marone LK, et al. Predictors of failure and successof tibial interventions for critical limb ischemia. J Vasc Surg 2010;52:834–42.

2. Schmidt A, Ulrich M, Winkler B, et al. Angiographic patency andclinical outcome after balloon-angioplasty for extensive infrapoplitealarterial disease. Catheter Cardiovasc Interv 2010;76:1047–54.

Figure 2 Midterm Clinical Outcome

Bar graph showing Rutherford-Becker categories at baseline and12.5 months of follow-up (FU).

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3. Scheinert D, Ulrich M, Scheinert S, et al. Comparison of sirolimus-eluting vs. bare-metal stents for the treatment of infrapopliteal obstruc-tions. EuroIntervention 2006;2:169–74.

4. Scheller B, Hehrlein C, Bocksch W, et al. Treatment of coronaryin-stent restenosis with a paclitaxel-coated balloon catheter. N EnglJ Med 2006;355:2113–24.

5. Tepe G, Zeller T, Albrecht T, et al. Local delivery of paclitaxel toinhibit restenosis during angioplasty of the leg. N Engl J Med2008;358:689–99.

6. Werk M, Langer S, Reinkensmeier B, et al. Inhibition of restenosisin femoropopliteal arteries: paclitaxel-coated versus uncoated bal-

loon: femoral paclitaxel randomized pilot trial. Circulation 2008;118:1358 – 65.

7. Ferraresi R, Centola M, Ferlini M, et al. Long-term outcomes afterangioplasty of isolated, below-the-knee arteries in diabetic patientswith critical limb ischemia. Eur J Vasc Endovasc Surg 2009;37:336 – 42.

Key Words: critical limb ischemia y drug-eluting balloons y restenosisy tibial arteries.

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IN.PACT AmphirionPACLITAXEL!ELUTING PTA BALLOON CATHETER 0.014"

IN.PACT drug eluting balloon superior to PTA in CLI BtK patientsData presented at LINC 2012 by Dr. Liistro, Arezzo, Italy

STUDY PURPOSETo investigate whether DEB can reduce long-term restenosis rate compared to conventional balloon in diabetic patients with CLI undergoing peripheral intervention in tibial vessels.

PRIMARY AND SECONDARY ENDPOINTS - The primary endpoint was 12 months re-stenosis rate- Secondary endpoint: target lesion reocclusion

STUDY METHODS- Investigator sponsored single-center randomized (1:1) trial- Angiographic follow-up at 12 months

PATIENT DEMOGRAPHICS AND LESION CHARACTERISTICS

DEBATE BTK

* Randomized Data for the Treatment of Below the Knee Lesions with Drug Eluting Balloons!

Dr. Francesco Liistro Department of Cardiovascular Disease,

San Donato Hospital, 52100 Arezzo, Italy presented at LINC 2012

DEBATE BTK "PRELIMINARY RESULTS#*

DRUG!ELUTING BALLOONS FOR LOWER LIMB ARTERIAL DISEASE

DEB (n=60) POBA (n=60)

Age 74±10 76±10

Hypertension 79% 83%

Hypercholesterolemia 25% 25%

Reference Vessel Diameter 2.86mm 2.82mm

Occlusion 80% 82%

Mean Lesion Length 121mm 123mm

BTKCLI/DIABETICS

STATUS DATE: 02/2012

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IN.PACT AmphirionPACLITAXEL!ELUTING PTA BALLOON CATHETER 0.014”

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CONCLUSION

By preliminary study results, DEB seem to provide better results in terms of 12 months restenosis and reocclusion compared to POBA in the revascularization of tibial vessels in diabetic patients with CLI.

DEBATE BTK "PRELIMINARY RESULTS#*

IN.PACT drug eluting balloon superior to PTA in CLI BtK patients

12 MONTHS RESULTS !ANGIOGRAPHIC AND CLINICAL"

DEB (n=60) POBA (n=60) P value

Death 6% 4% 0.2

Major Amputation 0 1

12 months restenosis 29% 72% 0.0004

12 months reocclusion 14% 50% 0.0006

70% –

60% –

50% –

40% –

30% –

20% –

10% –

0% –Re-stenosis Re-occlusion

DEB

POBA

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50.0%

14.0%

29.0%

p=0.0004

p=0.0006

STATUS DATE: 02/2012

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IN.PACT DEB TECHNOLOGY

CLINICAL TRIAL OVERVIEW

SFA RESULTS

BTK RESULTS

IN.PACT DEB Technology andClinical Evidence

ORDER INFORMATION

& ABBREVATIONS

Order Information

Abbreviations

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ORDERINFORMATION

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ORDER INFORMATION

Ref. N° 80 cm shaft length

Ref. N° 130 cm shaft length

Balloon diameter

(mm)

Balloon length (mm)

Recom. introducer sheath (F)

RBP (bar)

SBI 040 040 08P SBI 040 040 13P 4 40 5 18SBI 040 060 08P SBI 040 060 13P 4 60 5 18SBI 040 080 08P SBI 040 080 13P 4 80 5 18SBI 040 120 08P SBI 040 120 13P 4 120 5 18SBI 050 040 08P SBI 050 040 13P 5 40 6 17SBI 050 060 08P SBI 050 060 13P 5 60 6 17SBI 050 080 08P SBI 050 080 13P 5 80 6 15SBI 050 120 08P SBI 050 120 13P 5 120 6 15SBI 060 040 08P SBI 060 040 13P 6 40 6 17SBI 060 060 08P SBI 060 060 13P 6 60 6 17SBI 060 080 08P SBI 060 080 13P 6 80 6 15SBI 060 120 08P SBI 060 120 13P 6 120 6 15SBI 070 040 08P SBI 070 040 13P 7 40 6 16SBI 070 060 08P SBI 070 060 13P 7 60 6 14SBI 070 080 08P SBI 070 080 13P 7 80 6 14

Ref N°90 cm shaft length

Ref N° 130 cm shaft length

Balloon diameter

(mm)

Balloon length(mm)

Recom. Introducer sheath (F)

RBP (bar)

PCF 040 040 09P PCF 040 040 13P 4.00 40 5 20PCF 040 060 09P PCF 040 060 13P 4.00 60 5 14PCF 040 080 09P PCF 040 080 13P 4.00 80 5 14PCF 040 120 09P PCF 040 120 13P 4.00 120 5 14PCF 050 040 09P PCF 050 040 13P 5.00 40 5 20PCF 050 060 09P PCF 050 060 13P 5.00 60 5 14PCF 050 080 09P PCF 050 080 13P 5.00 80 5 14PCF 050 120 09P PCF 050 120 13P 5.00 120 5 14PCF 060 040 09P PCF 060 040 13P 6.00 40 5 16PCF 060 060 09P PCF 060 060 13P 6.00 60 5 14PCF 060 080 09P PCF 060 080 13P 6.00 80 5 14PCF 060 120 09P PCF 060 120 13P 6.00 120 5 14PCF 070 040 09P PCF 070 040 13P 7.00 40 6 12PCF 070 060 09P PCF 070 060 13P 7.00 60 6 12PCF 070 080 09P PCF 070 080 13P 7.00 80 6 12PCF 070 120 09P PCF 070 120 13P 7.00 120 6 12

Ref. N° 120 cm shaft length

Ref. N° 150 cm shaft length

Balloon diameter

(mm)

Balloon length (mm)

Recom. Introducer sheath (F)

RBP(bar)

AMD 020 040 00P AMD 020 040 15P 2.00 40 4 15AMD 020 080 00P AMD 020 080 15P 2.00 80 4 14AMD 020 120 00P AMD 020 120 15P 2.00 120 4 14AMD 025 040 00P AMD 025 040 15P 2.50 40 4 16AMD 025 080 00P AMD 025 080 15P 2.50 80 4 15AMD 025 120 00P AMD 025 120 15P 2.50 120 4 14AMD 030 040 00P AMD 030 040 15P 3.00 40 4 16AMD 030 080 00P AMD 030 080 15P 3.00 80 4 15AMD 030 120 00P AMD 030 120 15P 3.00 120 4 14AMD 035 040 00P AMD 035 040 15P 3.50 40 4 16AMD 035 080 00P AMD 035 080 15P 3.50 80 4 15AMD 035 120 00P AMD 035 120 15P 3.50 120 4 14AMD 040 040 00P AMD 040 040 15P 4.00 40 4 16AMD 040 080 00P AMD 040 080 15P 4.00 80 4 15AMD 040 120 00P AMD 040 120 15P 4.00 120 4 14

IN.PACT AdmiralPACLITAXEL!ELUTING PTA BALLOON CATHETER OTW 0.035"

IN.PACT PacificPACLITAXEL!ELUTING PTA BALLOON CATHETER OTW 0.018"

IN.PACT AmphirionPACLITAXEL!ELUTING PTA BALLOON CATHETER OTW 0.014"

Global HeadquartersHungerbüelstrasse 128500 Frauenfeld – Switzerland

www.medtronic.comwww.invatec.com

Page 27: Medtronic In.Pact Clinical Evidence

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ABBREVIATIONS

ABI Ankle Brachial Index

BTK Below The Knee

DEB Drug Eluting Balloon

DS Diameter stenosis

GFR Glomerular Filtration Rate

ITT Intention To Treat

LLL Late Lumen Loss = MLD (at follow up) - MLD (post-procedure)

MACE Major Adverse Clinical Effects

MLD Minimum Luminal Diameter

PP Per Protocol

PSVR Peak Systolic Velocity Ratio

PTA Percutanous Transluminal Angioplasty

RC Rutherford Classification

RR Restenosis Rate Binary Restenosis= DS > 50% of treated lesion at follow-up

RVD Reference Vessel Diameter

SFA Superficial Femoral Artery

TLR Target Lesion Revascularization

TVR Target Vessel Revascularization

US Ultrasound

USCD Ultrasound Color Doppler

Global HeadquartersHungerbüelstrasse 128500 Frauenfeld – Switzerland

www.medtronic.comwww.invatec.com