5 Year Results from the IN.PACT SFA Randomized Trial

John R. Laird, MD

Adventist Heart and Vascular Institute

St. Helena, CA

DisclosuresJohn R. Laird

• Within the past 12 months, I or my spouse/partner have had a financial

interest/arrangement or affiliation with the organization(s) listed below.

• Affiliation/Financial Relationship Company

• Consulting Fees/Honoraria Boston Scientific, Medtronic, Abbott, Bard/Becton

Dicksenson Peripheral Intervention, Philips

• Scientific Advisory board/stock options Reflow Medical, Endoluminal Sciences,

Syntervention, PQ Bypass, Eximo Medical,

Shockwave Medical, NexGen

Board Member VIVA Physicians

Background• Numerous randomized trials with drug-coated balloons (DCBs) have shown

improved outcomes of DCB over PTA2-10

• Published results of the IN.PACT SFA Trial have demonstrated superiority of the IN.PACT™ Admiral™ DCB over percutaneous transluminal angioplasty (PTA)2,7,8

• Long-term data from randomized trials for DCBs available in the U.S. is limited

1. Medtronic IFU M052624T0001_rev1H.2. Schneider P et al. Circ-CI 2018;11:1-15.3. Rosenfield K et al. NEJM 2015;373:145-53.4. Laurich C. LEVANT 2 Two-Year Results. SVS 2015.

5. Krishnan P et al. Circulation 2017;136:1102-1113.6. Mathews SJ. ILLUMENATE US Two-Year Results.

NCVH 2018.7. Tepe G et al. Circ 2015;131:495-502.

8. Laird JR et al. JACC 2015;66:2329-2338.9. Schneider P. IN.PACT SFA Four-Year Results. VIVA

2017.10. Laird JR. IN.PACT SFA Five-Year Results. VIVA 2018.

Primary Patency

1-Year 2-Year 3-Year 4-Year 5-Year

IN.PACT SFA IN.PACT™ DCB

87.5%1 79.0%1 69.5%2 Not assessed after 3 years

Levant IILutonix™* DCB

73.5%3 58.6%4 Not Reported Not Reported Not Reported

ILLUMENATE USStellarex™* DCB

82.3%5 72.1%6 Not Reported Not Reported Not Reported

1-Year 2-Year 3-Year 4-Year 5-Year

CD-TLR

IN.PACT SFA IN.PACT™ DCB

2.4%7 9.1%8 15.2%2 23.4%9 25.5%10

Levant IILutonix™* DCB

12.3%3 18.0%4 Not Reported Not Reported Not Reported

ILLUMENATE USStellarex™* DCB

7.9%5 Not Reported Not Reported Not Reported Not Reported

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IN.PACT SFA Trial*Overview

1. VasCore DUS Core Laboratory, Boston, MA, US; 2. SynvaCor Angiographic Core Laboratory, Springfield, IL, US; 3. Clinical Events Committee and Data Safety Monitoring services provided by HCRI, Boston, MA, US* Sponsored by Medtronic plc

Robust Level 1 Evidence

• Prospective, multicenter EU and US, randomized (2:1), single-blinded trial

• 331 patients enrolled: • IN.PACT DCB (n = 220) vs. PTA (n = 111)

Rigorous and Unbiased

• Independent and blinded Duplex Ultrasound Core Lab,1 Angiographic Core Lab,2 and Clinical Events Committee3

• Independent Safety Monitoring Board

• External monitoring with 100% source data verification

Durability of Outcomes

• Subjects followed up to 5 years

IN.PACT SFA I150 subjects enrolled at 13 EU

sites Sep 2010-Apr 2011

IN.PACT SFA II181 subjects enrolled at 44 US

sites Apr 2012-Jan 2013

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IN.PACT SFA Trial

IN.PACT SFA I150 subjects enrolled at 13 EU sites

Sep 2010-Apr 2011

IN.PACT SFA II181 subjects enrolled at 44 US sites Apr

2012-Jan 2013

M. Brodmann, Graz, Austria G. Sorropago, Mercogliano, Italy

G. Tepe, Rosenheim, Germany P. Peeters, Bonheiden, Belgium

T. Zeller, Bad Krozingen, Germany F. Vermassen, Gent, Belgium

D. Scheinert, Leipzig, Germany C. Trani, Rome, Italy

A. Micari, Palermo, Italy M. Bosiers, Dendermonde, Belgium

I. Baumgartner, Bern, Switzerland J. Van den Berg, Lugano, Switzerland

S. Sixt, Hamburg, Germany

P. Krishnan, New York, NY, USA C. Walker, Houma, LA, USA

C. Metzger, Kingsport, TN, USA N. Strickman, Houston, TX, USA

A. Jain, Fremont, CA, USA R. Fairman, Philadelphia, PA, USA

R. Sachar, Raleigh, NC, USA S. Laster, Kansas City, MO, USA

N. Farhat, Elyria, OH, USA W. Gray, New York, NY, USA

L. Garcia, Boston, MA, USA V. Ramaiah, Phoenix, AZ, USA

R. Malhotra, Glendale, AZ, USA P. Alden, Minneapolis, MN, USA

S. Germanwala, Longview, TX, USA C. Stinis, La Jolla, CA, USA

A. Pershad, Phoenix, AZ, USA R. Dave, Camp Hill, PA, USA

B. Bigelow, Indianapolis, IN, USA R. Gallino, Washington, DC, USA

J. Zidar, Raleigh, NC, USA G. Ansel, Columbus, OH, USA

S. Ahanchi, Norfolk, VA, USA M. Schermerhorn, Boston, MA, USA

R. Feldman, Ocala, FL, USA M. Hunter, Cincinnati, OH, USA

R. Kovach, Brown Mills, NJ, USA M. Dake, Stanford, CA, USA

M. Goodwin, Naperville, IL, USA J. Benenati, Miami, FL, USA

L. Marone, Pittsburgh, PA, USA P. Schneider, Honolulu, HI, USA

M. Shishehbor, Cleveland, OH, USA R. Serry, Poway, CA, USA

D. Chew, Des Moines, IA, USA J. Angle, Charlottesville, VA, USA

P. Soukas, Providence, RI, USA K. Gupta, Kansas City, KS, USA

M. Garcia, Newark, DE, USA P. Jones, Chicago, IL, USA

M. Mewissen, Milwaukee, WI, USA G. Petrossian, Roslyn, NY, USA

R. Brown, Waco, TX, USA A. Patel, Morristown, NJ, USA

1. Tepe G. et al. Circ 2015;131:495-5022. Laird J.R. et al. JACC 2015;66:2329-23383. Schneider P. et al. Circ-CI 2018;11:1-8 5

• MAEs (including all individual components of the primary endpoints and key secondary endpoints) are adjudicated by the blinded CEC through 5 years

• Restenosis is assessed by the blinded Duplex and Angiographic Core Labs through the 3-year follow-up visits

† Conducted via Telephone Interview

5 Year Follow-up Assessment†

• Clinically-driven TLR: CD-TLR was adjudicated by an independent Clinical Event Committee, blinded to the assigned treatment based on any re-intervention at the target lesion due to symptoms or drop of ABI of ≥20% or >0.15 when compared to post-procedure baseline ABI

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IN.PACT SFA TrialBlinded, Independently Assessed Outcomes

IN.PACT SFA TrialBaseline Characteristics

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IN.PACTn = 220 subjects

PTAn = 111 subjects

P-value

Age, Y ± SD 67.5 ± 9.5 68.0 ± 9.2 0.612

Male, % (n) 65.0% (143/220) 67.6% (75/111) 0.713

Diabetes, % (n) 40.5% (89/220) 48.6% (54/111) 0.161

Current Smoker, % (n) 38.6% (85/220) 36.0% (40/111) 0.719

Rutherford Class, % (n) 2345

37.7% (83/220)57.3% (126/220)

5.0% (11/220)0.0% (0/220)

37.8% (42/111)55.9% (62/111)

5.4% (6/111)0.9% (1/111)

0.898

Lesion Length (cm± SD) 8.94 ± 4.89 8.81 ± 5.12 0.815

Total Occlusions, % (n) 25.8% (57/221) 19.5% (22/113) 0.222

Calcification, % (n) 59.3% (131/221) 58.4% (66/113) 0.907

Severe Calcification, % (n) 8.1% (18/221) 6.2% (7/113) 0.662

Provisional Stenting, % (n) 7.3% (16/220) 12.6% (14/111) 0.110

IN.PACT SFA TrialFreedom from CD-TLR through 5 Years

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IN.PACT SFA TrialEffectiveness Outcomes through 5 Years

1. Clinically-driven TLR adjudicated by an independent Clinical Event Committee, blinded to the assigned treatment based on any re-intervention at the target lesion due to symptoms or drop of ABI of ≥20% or >0.15 when compared to post-procedure baseline ABI

2. Any TLR includes clinically-driven and incidental or duplex driven TLR

† Unless otherwise indicated, all tests were for superiority using the Fisher’s exact test for binary variables and t-test for continuous variables.

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IN.PACT DCB (N=220)

PTA(N=111)

P-value†

CD-TLR1 25.5% (47/184) 35.6% (37/104) 0.080

Any TLR2 26.6% (49/184) 37.5% (39/104) 0.063

Time to CD-TLR within 1800 Days (Min, Max days)

807.5 ± 433.9(1, 1701)

474.9 ± 484.3(1, 1705)

< 0.001

IN.PACT SFA TrialSafety Outcomes through 5 Years

1. Safety Composite Endpoint consists of: freedom from device/procedure related death to 30 days; freedom from target limb amputation within 60 months; and freedom from clinically-driven TVR within 60 months.

2. Composite of death, clinically-driven TVR, target limb major amputation, and thrombosis3. All deaths adjudicated by the CEC† P-values are based on Fisher’s exact test for superiority with significance level of 0.05

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IN.PACT DCB (N=220)

PTA(N=111)

P-value†

Primary Safety Composite1 70.7% (130/184) 59.6% (62/104) 0.068

Major Adverse Events2 42.9% (79/184) 48.1% (50/104) 0.459

All-cause Death 15.8% (29/184) 9.6% (10/104) 0.156

Device- or Procedure-related Death through 5 Years3

0 (0/184) 0 (0/104) --

CD-TVR 29.3% (54/184) 40.4% (42/104) 0.068

Major Target Limb Amputation

0.5% (1/184) 0.0% (0/104) 1.000

Thrombosis 2.2% (4/184) 4.8% (5/104) 0.292

IN.PACT SFA Trial: All-cause DeathNo Device or Procedure-related Deaths

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All-cause Death Through 5 Years CEC-Adjudicated

DCB(N=184)

PTA(N=104)

Device-related

Procedure-Related

Cardiac-related 3.3% (6) 1.0% (1) No No

Malignancy-related 2.7% (5) 3.9% (4) No No

Respiratory-related 1.6% (3) 0.0% (0) No No

Neurological-related 2.2% (4) 0.0% (0) No No

Hepatobiliary-related 0.5% (1) 0.0% (0) No No

Gastrointestinal-related

1.6% (3) 1.9% (2) No No

Renal-related 0.5% (1) 0.0% (0) No No

Infection-related 1.1% (2) 0.0% (0) No No

Other 0.5% (1) 1.9% (2) No No

Unknown 1.6% (3) 1.0% (1) No No

Categorized by system-class

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IN.PACT SFA Trial through 5 YearsNo Relationship between Paclitaxel Dose and

Mortality Rate

o = outlier ◊ = mean

IN.PACT SFA Trial Through the Years

1. Medtronic IFU M052624T001_Rev1H2. Schneider P. et al. Circ-CI 2018;11:1-8

14*p-value compares DCB to PTA

IN.PACT SFA Trial Through the Years

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1. Tepe G. et al. Circ 2015;131:495-5022. Laird J.R. et al. JACC 2015;66:2329-23383. Schneider P. et al. Circ-CI 2018;11:1-84. Schneider P. VIVA 2017 5. Laird J.R. VIVA 2018*p-value compares DCB to PTA

Summary• First independently adjudicated, blinded, randomized trial to demonstrate

superior effectiveness of a drug-coated balloon (DCB) through five years.

• This final report of the IN.PACT SFA Trial demonstrates long-term safety of

the IN.PACT™ Admiral™ DCB through 5 years

– No device- or procedure-related deaths through 5 years

– Low thrombosis rates through 5 years

– No relationship between paclitaxel dose among those who died versus

survived

• The IN.PACT SFA Trial demonstrates durable effectiveness of the IN.PACT™

Admiral™ DCB

• Results support DCB as a first line strategy for the treatment of

femoropopliteal disease

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Thank You

5 Year Results from the IN.PACT SFA Randomized Trial

John R. Laird, MD

Adventist Heart and Vascular Institute

St. Helena, CA