Bare Metal Stent Self Expandable Stent Balloon Expandable Stent

Balloon-Expandable Stents – Overview Formula Formula 414 RX Vascular Formula 418 Vascular Formula 535 Vascular

Balloon-Expandable Stents – Overview

Zilver Stent with history and development 2009: Launch of Zilver PTX 7 Fr 2004: Launch of Zilver 635 2009: Launch of Zilver Flex 2011: Launch of Zilver PTX 6 Fr 2003: Launch of Zilver 518 2008: Launch of Zilver 518RX 2015: Launch of New delivery system Zilver PTX 2011: Launch of Zilver Vena 2001: Launch of Zilver 735 Zilver 735 obsoleted Zilver PTX Thumbleweel 2015 2000 2015

Nitinol Nickel Titanium Naval Ordinance Laboratory Superelastic alloy Memory shape material Has lowest fatigue-crack growth resistance of metallic alloys used for implant Ni Ti N O L Nitinol is an alloy between Nickel and Titanium

BES vs. SES

Open Cell vs. Closed Cell Open Cell: - More flexible - Conforms to vessel wall better - Less metal in smaller vessels Closed Cell: - More radial force - Greater plaque coverage All Cooks zilver stents platform is with Open Cell design. Tanaka N, Martin JB, Tokunaga K, et al. Conformity of carotid stents with vascular anatomy: evaluation in carotid models. AJNR Am J Neuroradiol. 2004; 25(4):604-607. Silva M. Debate: open cell stents are superior! Presented at: ICCA V 5th International Course on Carotid Angioplasty and Other Cerebrovascular Interventions; October 28, 2005; Frankfurt, Germany.

Zilver® Flex™35 - Box

Zilver Flex 35 Linear connectors result in more uniform load distribution and more stable deployment characteristics (no twisting or elongation) Even though we designed more tie bars we did not compromissed with the flexibility

Zilver Flex 35 Tie-bar connectors alternate direction resulting in enhanced axial fatigue And still provids better result for enhancing the axial (compression) fatigue/fracture rate.

Physician Preferences Self-Expandable Stent When to use what? Physician Preferences Self-Expandable Stent Balloon-Expandable Stent SES and BES are perfect substitutes Explain that from a sales perceptive – it is always the physicians preferences this the most important. We do not mind if he use a SX or BX stent.

When to use what? BES: “The high radial strength of the balloon expandable stents and the lack of foreshortening make them suitable, in particular, for ostial or severely calcified lesions."   Source: Manual of peripheral vascular intervention, Casserly, I. P. et al., 2005 by Lippincott Williams & Wilkins, USA Common iliac

When to use what? SFA Se ”Papir”

Zilver PTX

The Only Drug Eluting Peripheral Stent for the SFA Backgound Launched in Europe in 2009 More than 250,000 patients treated Sold on 6 continents 5 year clinical data follow-up Late 1980s: Cook starts working on DES in the with coronary stents Mid 1990s: Cook begins working on paclitaxel-coated coronary DES Demonstrated effectiveness in two clinical studies (ASPECT and ELUTES) using a similar polymer-free paclitaxel coating as that on the Zilver PTX ASPECT: Randomized Clinical Study with approximately 60 patients each with bare metal and paclitaxel-coated Supra G stents. Effectiveness clearly demonstrated with 6-month restenosis rates of 27% and 4%, respectively ELUTES: Randomized Clinical Study with approximately 40 patients each with bare metal and paclitaxel-coated V-Flex Plus stents. Effectiveness clearly demonstrated with 6-month restenosis rates of 21% and 3%, respectively Obtained CE Mark and commercialized the V-Flex Plus PTX coronary stent in Europe 2000 Devt work ZPTX, Randomized 2005 2012: Japan(1)/USA(2) Proven Drug Effect

Mechanical Therapy: Established Technology Stent Platform Zilver® PTX® is based on the next-generation Zilver Flex stent platform The stent is known for its balance of flexibility, fracture resistance, and radial force The combination of drug-elution and a strong yet flexible scaffold is the standard of care for SFA lesions

Drug Therapy: Paclitaxel coating (PTX) Zilver PTX Drug-Eluting Peripheral Stent New generation SFA Stent Available in over 50 countries Approved in EU, Japan, and US Scaffold plus drug Mechanical scaffold: Zilver Flex® Stent Platform Drug therapy: Paclitaxel only No polymer or binder 3 µg/mm2 dose density Uncoated PTX Coated

Why Are Drugs Used? To reduce restenosis To inhibit smooth muscle cell proliferation Reduce inflammation

X Paclitaxel Natural substance from the bark of (Taxus Brevifolia) Western Yew tree Originally developed and used as a cancer drug to stop cell proliferation X

Mechanism of Action Normal cell cycle PTX effect on cell cycle A normal cell cycle is when a cell replicates into two new cells. PTX effect on cell cycle Paclitaxel stops the cell cycle in phase M (mitosis) and therefore prevents the cell from replicating into two new cells

Why we need drug-eluting devices? Paclitaxel (PTX) permanently prevents cell division Reduces restenosis Inhibits smooth muscle cell proliferation Reduces inflammation

Intended use The Zilver PTX Drug Eluting Peripheral Stent is intended for use in the treatment of… symptomatic vascular disease of the above-the-knee femoropopliteal arteries having reference… vessel diameter from 4 mm to 7 mm. To avoid involvement of the common femoral artery, the proximal end of the stent should be placed… at least 1 cm below the origin of the superficial femoral artery. To avoid involvement of the below-the-knee popliteal artery, the distal end of the stent should be placed… above the plane of the femoral epicondyles. The intended use for Zilver PTX is for the treatment of de novo or restenostic symptomatic lesions in the above the knee fempop arteries. The preliminary sizes available will be for lesions 4-6 mm in diameter and lengths up to 140 mm per limb and 280 mm per patient. (Vessel size 4-6 mm of SFA)

Stent sizing Sizing recommendations are similar to standard bare metal stents. Measure the diameter of the reference vessel (proximal and distal to the lesion) and use the largest reference diameter as your basis for choosing the appropriate stent size. The stent size should be selected so that the unconstrained stent diameter is at least 1 mm larger than the reference vessel diameter and no more than 2 mm larger than the reference vessel diameter. Stent sizing can be determined exactly as you would for BMS by measuring the RVD and upsizing the stent at least 1 mm larger and no more than 2 mm larger than it.

Available product configurations Stent diameters 5, 6, 7 and 8 mm Stent length 40, 60, 80, 100 and 120 mm Delivery system 6 Fr Delivery system length 80 cm and 125 cm Cook wants to make Zilver PTX available to as many patients as possible. Therefore, initially, only two sizes will be available to work with supplying the demand. That will be the 6 x 80 and the 7 x 80 on a 6 Fr, 125 cm delivery system. We will continue to expand the sizes as we move forward. (40, 60 mm lengths, 8 mm diameter, longer lengths)

Zilver PTX - Superior Results

Zilver PTX – two key trials RCT: 2005 SAT: 2006

5-year Freedom from TLR Zilver PTX vs. Standard Care 83.1% Zilver PTX p < 0.01 log-rank Optimal PTA + BMS 67.6% At 5 years, Zilver PTX demonstrates a 48% reduction in reintervention compared to standard care

5-year Primary Patency (PSVR < 2.0) Zilver PTX vs. Standard Care 66.4% Zilver PTX p < 0.01 log-rank Optimal PTA + BMS 43.4% At 5 years, Zilver PTX demonstrates a 41% reduction in restenosis compared to standard care

5-year Primary Patency (PSVR < 2.0) Zilver PTX vs. Standard Care 66.4% Zilver PTX Optimal PTA + BMS 43.4% From 1-5 years, the relative separation increases by 35%

5-year Freedom from TLR Provisional Zilver PTX vs. BMS 84.9% Provisional Zilver PTX p = 0.06 log-rank 71.6% Provisional BMS At 5 years, Zilver PTX demonstrates a 47% reduction in reintervention compared to BMS

5-year Primary Patency (PSVR < 2.0) Provisional Zilver PTX vs. BMS 72.4% p = 0.03 log-rank 53.0% Provisional BMS At 5 years, Zilver PTX demonstrates a 41% reduction in restenosis compared to BMS

Do it right the first time! Zilver PTX has a proven drug effect in the SFA. Cook Medical would like offer training to hospital staff to help get them onboard with drug elution in the periphery.