Zilver PTX Trial

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Zilver PTX Trial

• Bhagat K. Reddy, MD, FACC
• Director of Vascular Medicine Endovascular
  Interventions
• Piedmont Heart Institute
• Atlanta, GA

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Zilver PTX Clinical Trials

• Global Sponsor Cook Incorporated
• Physician Steering Committees
• Michael Dake, M.D. (Global Principal
  Investigator)

• Registry Study
• Gunnar Tepe, M.D.
• Fabrizio Fanelli, M.D.
• Dierk Scheinert, M.D.
• Jöerg Tessarak, M.D.

• Randomized Study
• Gary Ansel, M.D. (co-PI)
• Michael Jaff, D.O.
• Lindsay Machan, M.D.
• Takao Ohki, M.D., Ph.D.
• Richard Saxon, M.D.
• H. Bob Smouse, M.D.

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Registry Study Site Enrolled Registry Study Site Enrolled
Herz-Zentrum (Bad Krozingen, Germany) 153 Seoul National University Hospital (Seoul, Korea) 12
Heart Center Leipzig, Angiology (Leipzig, Germany) 110 Hospital Universitario La Fe (Valencia, Spain) 12
Gemeinschaftspraxis (Leipzig, Germany) 69 Samodzielny Publicczny (Lublin, Poland) 11
St. Blasius Hospital, Dendermonde (Dendermonde, Belgium) 50 St. Francois (Quebec, Canada) 10
Imelda Hospital, Bonheiden (Bonheiden, Belgium) 47 Samsung Medical Center (Seoul, Korea) 10
Endosurgery and Lithotripsy Center (Moscow, Russian Federation) 45 Hospital Europeen Georges Pompidou (Paris, France) 10
Universitat Klinik Tubingen (Tubingen, Germany) 42 Centrum Medyczne (Katowice, Poland) 10
St. Franziskus Hospital Münster (Münster, Germany) 34 Malmo Univeritetssjukhus (Malmo, Sweden) 9
University Hospital Ostrava-Poruba (Ostrava-Poruba, Czech Republic) 27 University Hospital Antwerp (Edegem, Belgium) 7
Center for Cardiology Vascular Intervention Praxis (Hamburg, Germany) 24 Zurich University Hospital (Zurich, Switzerland) 5
Careggi Hospital (Florence, Italy) 20 Catharina Hospital (Eindhoven, The Netherlands) 5
University of Roma La Sapienza (Rome, Italy) 15 Policlinico G. B. Rossi (Verona, Italy) 4
Amphia Hospital (Breda, The Netherlands) 15 Hospital Clinic of Barcelona (Barcelona, Spain) 4
Centre Hospitalier Universitaire de Sherbrooke (Sherbrooke, Canada) 13 Hospital Jean Minjoz (Besancon Cedex, France) 3
Asan Medical Center (Seoul, Korea) 13 Hospital Clinico Universitario (Valencia, Spain) 3
Total Enrollment 792 patients at 30
investigative sites
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Zilver PTX

• Paclitaxel only
• No polymer or binder
• 3 µg/mm2 dose density
• Zilver, self-expanding nitinol stent
• Flexible, durable platform

Uncoated
PTX Coated
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Zilver PTXIndication

• Treatment of symptomatic disease of the
  above-the-knee femoropopliteal artery
• Proximal 1 cm below bifurcation
• Distal medial femoral epicondyle
• Reference vessel diameter of 4 - 9 mm

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Clinical Trial Status

• Randomized Study (480 patients)
• United States, Japan and Germany
• Enrollment complete
• Registry Study (792 patients)
• Europe, Russia, Canada and Korea
• Patients treated with Zilver PTX stents
• Enrollment complete

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Registry Study

• Patients assigned to Zilver PTX only
  
• Includes complex SFA lesions (nearly all
  comers)
• Rutherford category 2 or greater
• No lesion length limitation
• Up to 4 DES per patient - longest stent 8 cm
• Multiple lesions per leg
• Stenosis ( 50 DS), occlusion, re-stenosis,
  in-stent restenosis
• Follow-up through 2 years
• Currently available data
• 12-month follow-up for 592 patients (673 lesions)
• 24-month follow-up for 177 patients (221 lesions)

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Demographics
12 Months 24 Months
Overall Patients (n) 592 177
Age (years) 67 9 66 9
Male 73 76
Height (cm) 170 9 170 8
Weight (kg) 79 15 77 15
Diabetes 35 36
High Cholesterol 59 63
Hypertension 82 83
Past/Current Smoker 80 83
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Baseline Angiographic Data
12 Months 24 Months
Overall Lesions (n) 673 221
Lesion Length (cm) 9.4 7.8 9.3 8.0
Proximal RVD (mm) 5.4 0.8 5.4 0.8
Distal RVD (mm) 5.3 0.8 5.3 0.8
MLD in Lesion (mm) 0.84 0.88 0.76 0.73
Diameter Stenosis 84 17 86 14
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Lesion Characteristics
    12 Months 24 Months
Patients Patients 592 177
Lesions Lesions 673 221
Lesion Characteristics TASC class A 28 22
Lesion Characteristics B 30 36
Lesion Characteristics C 25 27
Lesion Characteristics D 13 13
Lesion Characteristics gt 7 cm 46 46
Lesion Characteristics Total Occlusion 36 33
Lesion Characteristics Restenosis (all) 25 37
Lesion Characteristics In-stent Restenosis 16 24
TASC 2000
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Results

• Stent Integrity
• Safety
• Effectiveness

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Stent Integrity
Time Period Potential Fractures
6 Months 1.4 (21/1486)
12 Months 1.8 (21/1198)
Pending core lab confirmation (rates may
decrease) Zilver PTX Registry did not include
stent X-rays at 24-month follow-up
Integrity data for the Zilver stent platform are
also available for 96 stents implanted in the
femoropopliteal arteries (above, behind and below
the knee) of 34 patients, with a mean follow-up
of 2.4 years, showing a 1 fracture rate (1/96,
stents). Ferriera, et al., Eur J Vasc Endovasc
Surg 34, 707-708, 2007
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Safety Event-free Survival

• Event-free survival defined as freedom from
• Death, amputation (toe, foot, or leg)
• Revascularization
• Clinically driven re-intervention for gt 50 DS
  within treated segment (including 5 mm)
• Surgical bypass of target vessel
• Worsening of Rutherford Classification
• (by two classes or to a Class 5 or 6)

12 Months 24 Months
Patients 596 181
Event-free Survival 87 78
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EffectivenessFreedom from TLR

• TLR defined as
• Clinically driven re-intervention for gt 50 DS
  within treated segment (including 5 mm)

12 Months 24 Months
Patients 593 177
Lesions 675 221
Freedom from TLR 89 82
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Freedom from TLR
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Clinical Outcomes
Clinical Measure Pre-procedure 12 Months 24 Months
ABI 0.65 0.26 (n 686) 0.90 0.24 (n 582) 0.88 0.21 (n 161)
Most Common Rutherford Score 3 (n 433/763) 0 (n 290/563) 0 (n 77/171)
Walking Distance Score 31 26 (n 659) 71 32 (n 565) 68 33 (n 158)
Walking Speed Score 35 28 (n 643) 66 31 (n 553) 67 31 (n 156)
p lt 0.01 compared to pre-procedure
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Freedom from TLR
Subgroup 12 Months 24 Months
Overall 89 (n 674) 82 (n 221)
TASC C and D 86 (n 225) 75 (n 87)

De novo 92 (n 501) 88 (n 139)
Restenosis (all) 81 (n 170) 72 (n 81)
Restenosis (not ISR) 86 (n 64) 69 (n 29)
In-stent Restenosis (ISR) 76 (n 106) 73 (n 52)

lt 7cm Lesions 94 (n 355) 91 (n 116)
gt 7 to 14 cm Lesions 89 (n 158) 72 (n 53)
gt 14 cm Lesions 77 (n 154) 73 (n 49)

Occlusions 86 (n 429) 78 (n 72)
Stenosis 90 (n 243) 85 (n 149)
TASC 2000
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Literature ComparisonsTLR at 12 Months
Literature Literature Literature Matching Registry Subset
Study Inclusion Criteria TLR 12 Months TLR 12 Months
Resilient (Katzen ISET 2008) No in-stent restenosis Lesion length lt 15 cm Rutherford 1-3 LifeStent 13 (n 153) Zilver PTX 5 (n 402) Excluded ISR, lesions gt 15 cm and Rutherford gt 3
FAST (Krankenberg 2007) De novo lesions Length 1 - 10 cm Multiple lesions lt 10 cm total 70 DS Luminexx Stent 15 (n 127) Zilver PTX 5 (n 237) Excluded RS lesions and lesions lt 1 cm or gt 10 cm
Durability (Scheinert TCT 2008) No in-stent restenosis Lesion length 14 Rutherford 2-4 Protégé EverFlex Stent 21 (n 134) Zilver PTX 6 (n 133) Excluded ISR, lesions gt14, lt 7 cm and Rutherford lt 2 or gt 4
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Literature ComparisonsTLR at 24 Months
Literature Literature Literature Matching Registry Subset
Study Inclusion Criteria TLR 24 Months TLR 24 Months
Resilient (Katzen VEITH 2008) No in-stent restenosis Lesion length lt 15 cm Rutherford 1-3 LifeStent 20 (n 153) Zilver PTX 8 (n 115) Excluded ISR, lesions gt 15 cm and Rutherford gt 3
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Conclusions

• The Zilver stent platform appears to have
  excellent durability (i.e., fracture resistance)
  in the SFA
• Results through 2 years with the Zilver PTX
  stent show
• No safety concerns apparent
• Favorable effectiveness (TLR rates, clinical
  outcomes, comparison to literature)