1. Lutonix® Paclitaxel-Coated Balloon to Treat Obstructive Lesions in the Superficial Femoral and Popliteal Arteries Preliminary Six-Month Results from the SAFE-DCB Study
Nicolas W. Shammas, MD, MS and Edward Y. Woo, MD
for the SAFE-DCB Investigators

2. Nicolas W Shammas, MD, MS, FACC, FSCAI
Disclosures
Nicolas W Shammas, MD, MS, FACC, FSCAI
 Relevant Conflict of Interest
Research Support
Bard
Boston Scientific
 Consultant/Honoraria

3. Primary Patency (KM) at 365 Days
Background: LEVANT 2
Randomized, Controlled Trial Comparing the Lutonix® DCB to Standard Balloon Angioplasty in Femoropopliteal Arteries
LEVANT 2 resulted in:
Superior Primary Patency to PTA at 12 Months
Comparable Safety compared to PTA^
Numerically, but not statistically, lower TLR rate (12.3% Lutonix DCB vs. 16.8% PTA at 12 months)*
73.5%
56.8%
Primary Patency (KM) at 365 Days
P = 0.001
^Freedom from primary safety event at 365 days (86.7% Lutonix DCB vs. 81.5% PTA)
*TLR was a secondary endpoint. LEVANT 2 was not powered to detect TLR differences

4. There is a need for real-world data with the Lutonix Balloon
Background: LEVANT 2
LEVANT 2 included:
92.1% claudicants (Rutherford 2 & 3)
Mean lesion length: 62.8±41.0mm
97.8% TASC II A & B lesions
LEVANT 2 excluded:
Rutherford 5 & 6
Lesions > 15 cm in length
Patients that were likely to require provisional stent placement:
Patients with a major flow-limiting dissection and > 70% residual stenosis after pre-dilation were treated per standard of care
Note: The bail-out stent rate was low in LEVANT 2 (2.5% Lutonix DCB vs. 6.9% PTA)
Use of atherectomy, laser, cryoplasty, or scoring/focal-force balloons
There is a need for real-world data with the Lutonix Balloon

6. LEVANT 2 vs. LEVANT Global Registry

7. LEVANT Global Registry*
LEVANT 2 vs. LEVANT Global Registry
LEVANT Global Registry*
LEVANT 2#
(DCB Group)
12-Month TLR Rate^, % (n/N)
6.4 (41/639)
12.3 (35/285)
Freedom from TLR**, % [95% CI] (365 days)
94.2 [92.2, 95.8]
89.7 [85.7, 92.7]
12-Month Primary Patency Rate^, % (n/N)
82.5 (484/587)
65.2 (172/264)
Primary Patency**, % [95% CI] (365 days)
85.1 [82.0, 87.7]
73.5 [68.0, 78.2]
*Interim analysis of the Global Registry (May 2016)
#Rosenfield et al. N Engl J Med 2015;373:
^Proportional-based analysis
**Kaplan-Meier estimate of survival
Primary Patency is defined as the absence of target lesion restenosis and freedom from target lesion revascularization (TLR).

8. SAFE-DCB Registry
Objective: Assess the Lutonix Drug-Coated Balloon (DCB) to Treat Obstructive Lesions in the Superficial Femoral and Popliteal Arteries in a “Real World” US Patient Population
Prospective, single arm, multicenter registry
enrolled 1006 patients in 74 U.S. centers
First patient enrolled: April 2015
Last patient enrolled: September 2016
Co-Principal Investigators: Nicolas Shammas, Edward Woo
Oversight committee and medical monitor reviewed safety events
Preliminary 30-day and 6-month outcomes are being presented today.
Primary endpoint analysis at 12 months
Ongoing follow up through 3 years

9. SAFE-DCB Recommended Procedure Steps
Adequately prepare the vessel (determined by the treating physician)
Recommended Procedural Step:
Transit time < 30 seconds
Inflation time ≥ 120 seconds
Pressure > 7 atm
Final Residual Stenosis < 20%
Dual antiplatelet therapy:
Pre-Procedure: According to current medical standards
After Procedure: Minimum of 4 weeks
Prolonged antiplatelet therapy (at the discretion of the physician)

10. Patients
N = 1006
602 currently with 30-day follow up
200 currently with 6-month follow up (discrete cohort at 6 months)
Indication: Obstructive de novo or restenotic lesions up to 150 mm in length in the superficial femoral or popliteal arteries (reference vessel diameters of 4-7 mm)
Study requirements were broad to allow for a real-world, heterogeneous patient population
Inclusion:
The patient fits within the above indication for use, is willing to comply with follow-up procedures and visits, and provides written informed consent
Exclusion:
The patient is unwilling or unable to comply with the follow-up procedures or visits
The patient has another medical condition, or is in another clinical study, that may confound the SAFE-DCB data or may prevent the patient from complying with the study requirements

11. Baseline Demographics
30-Day Group
6-Month Group
Number of Patients
602
200
Age, years + SD
Male/Female, %
56.5/43.5
54.5/45.5
Rutherford Category, % (n/N)
Category 1
1.0 (6/602)
0.0 (0/200)
Category 2
13.1 (79/602)
9.0 (18/200)
Category 3
42.9 (258/602)
41.5 (83/200)
Category 4
15.5 (93/602)
17.0 (34/200)
Category 5
14.1 (85/602)
15.0 (30/200)
Category 6
3.5 (21/602)
2.5 (5/200)
Unknown*
10.0 (60/602)
Mean Lesion Length, mm + SD
*Not reported/not standard of care

12. Endpoint Definitions
Primary Effectiveness: Freedom from target lesion revascularization (TLR) at 12 months defined as the first revascularization procedure (e.g., PTA, stent) after the initial study procedure
Primary Composite Safety: Freedom from device- or procedure-related perioperative death (< 30 days), target limb major amputation (above the ankle), and target vessel revascularization
Secondary Endpoints:
Acute Device & Procedure Success: < 30% residual stenosis of the target lesion after the index procedure and no peri-procedural complications (e.g., death, stroke, MI) prior to hospital discharge
Major Flow-Limiting Dissection
TLR & Target Vessel Revascularization (TVR)
Device- and procedure-related serious adverse events (SAEs)
12-Month Primary Patency: Freedom from restenosis (> 50%) determined by DUS (PSVR < 2.4) and/or no TLR (DUS & angiographic core lab)
Presented Today

13. Results 30-Day Group 6-Month Group
Acute Device & Procedural Success, % (n/N)
91.9 (552/601*)
91.5 (183/200)
Major Flow-Limiting Dissection^, % (n/N)
4.3 (26/602)
5.0 (10/200)
TLR, % (n/N)
0.5 (3/595)
4.3 (8/188)
TVR, % (n/N)
0.7 (4/595)
5.9 (11/188)
Device-Related SAE#, % (n/N)
2.4 (14/597)
1.6 (3/190)
Procedure-Related SAE, % (n/N)
5.7 (34/597)
6.8 (13/190)
Periprocedural (< 30 Days) Death, (n/N)
1.2 (7/602) --
All Cause Death, (n/N)
3.3 (20/602)
6.5 (13/200)
*Denominator based on evaluable patients-did not discontinue before 30 Days or have an event before discontinuation
^ Dissection Types D-F per the National Heart, Lung, and Blood Institute (NHLBI)
# Serious Adverse Events

14. Subset Analysis: Vessel Prep (30 Days)
Vessel Preparation
POBA only
Atherectomy
Specialty#
Number of Patients
195
280 77
Lesion Length, mm + SD
Acute Device & Procedural Success, %
91.8
93.2
84.4
Major Flow-Limiting Dissection^, % (n/N)
1.0 (2/195)
4.6 (13/280)
0.0 (0/77)
TLR, % (n/N)
0.5 (1/192)
0.7 (2/277)
1.3 (1/77)
TVR, % (n/N)
1.1 (3/277)
2.6 (2/77)
Device-Related SAE, % (n/N)
0.0 (0/192)
2.2 (6/278)
Procedure-Related SAE, % (n/N)
3.7 (7/192)
4.7 (13/278)
Periprocedural (< 30 Days) Death, (n/N)
1.5 (3/195)
1.1 (3/280)
#Cutting, scoring, and focal-force balloons
*Denominator based on evaluable patients-did not discontinue before 30 Days or have event before discontinuation
^ Dissection Types D-F per the National Heart, Lung, and Blood Institute (NHLBI)

15. Subset Analysis: Diabetic (30 Days)
Non-Diabetic
Number of Patients
314
288
Lesion Length, mm + SD
Acute Device & Procedural Success, %
92.0
91.7
Major Flow-Limiting Dissection^, % (n/N)
3.8 (12/314)
4.9 (14/288)
TLR, % (n/N)
0.7 (2/314)
0.4 (1/288)
TVR, % (n/N)
1.0 (3/314)
Device-Related SAE, % (n/N)
1.9 (6/314)
2.8 (8/288)
Procedure-Related SAE, % (n/N)
5.2 (16/314)
6.3 (18/288)
Periprocedural (< 30 Days) Death, (n/N)
*Denominator based on evaluable patients-did not discontinue before 30 Days or have event before discontinuation
^ Dissection Types D-F per the National Heart, Lung, and Blood Institute (NHLBI)

16. Case Study
This is the Kaplan-Meier survival analysis of primary patency.
At 6 months the lines separate at the time of follow up ultrasound. This time to event analysis shows superior patency in the Lutonix DCB group and the difference is sustained through 12 months.
The difference between arms at 12 months was significant, with a log rank p-value of less than

17. Summary
Preliminary data from the SAFE-DCB US registry demonstrate high procedural and device success with low TLR and TVR and low device-related SAE
30-Day Results (602 patients):
Acute Device & Procedural Success: 91.9%
TLR: 0.5%
TVR: 0.7%
Device-Related SAE: 2.4%
6-Month Results (200 patients):
With a limited amount of data available at 6 months, acute device & procedural success remains high while TLR (4.3%), TVR (5.9%), and device-related SAEs (1.6%) remain low
Confirmation of these early results await long-term, more complete data and analyses. Additional follow up is ongoing.
This is the Kaplan-Meier survival analysis of primary patency.
At 6 months the lines separate at the time of follow up ultrasound. This time to event analysis shows superior patency in the Lutonix DCB group and the difference is sustained through 12 months.
The difference between arms at 12 months was significant, with a log rank p-value of less than

18. THANK YOU