Will we ever see a dedicated bifurcated DES in clinical practice? Aaron V. Kaplan, M.D., F.A.C.C., F.S.C.A.I  Professor of Medicine (Cardiology) Director of Research Dartmouth Medical School Cardiac Catheterization Laboratories Dartmouth-Hitchcock Medical Center

Aaron V. Kaplan, M.D. Conflict-of -Interests Founder & Director: Tryton Medical Research Support: Abbot Vascular Medtronic Boston Scientific Edwards Lifesciences Practicing Interventional Cardiologist

Dedicated Bifurcation Stent? Need to answer the following Questions What is the unmet clinical need? Is the clinical need being addressed? Does this makes sense from a business perspective?

Dedicated Bifurcation Stent? Need to answer the following Questions What is the unmet clinical need? Is the clinical need being addressed? Does this makes sense from a business perspective?

Defining the Clinical Need ‘True’ Bifurcation Lesions involving large side branches Medina (1.1.1, 0.1.1, 1.0.1) Large Side Branch Large Myocardium at risk What about Provisional Stenting? Nordic 1 & BBC1 Population Smaller side branches Only treated ~1/3 of time

Provisional Stenting Small side branch without apparent disease

Provisional Stenting? Disease in BOTH main vessel & side branch large

Defining the Clinical Need ‘True’ Bifurcation Lesions involving large side branches Medina (1.1.1, 0.1.1, 1.0.1) Large Side Branch Large Myocardium at risk Nordic I & BBC1 Smaller side branches Only treated ~1/3 of time

Nordic I 1 Stent is all you need?

Nordic 1 MV (Provisional) MV + SB Treatment Strategy POBA if <TIMI 3 Stent if TIMI 0 after POBA SB treatment 32% of pts Treatment Strategy Culotte, ‘T’ or Crush Final Kissing Inflations Final Kiss in 74% of pts

Nordic 1 MV (Provisional) MV + SB Treatment Strategy Results POBA if <TIMI 3 Stent if TIMI 0 after POBA SB treatment 32% of pts Results Procedural CPK: 8%+ MACE* @ 6 mos: 2.9% *Mace definition excludes procedural MI +p = 0.01 Treatment Strategy Culotte, ‘T’ or Crush Final Kissing Inflations Final Kiss in 74% of pts Results Procedural CPK: 18%+ MACE @ 6 mos = 3.4%

Nordic 1 Implies SB with small territories Interventionist comfortable NOT treating Clinically Silent

Defining the Clinical Need ‘True’ Bifurcation Lesions involving large side branches Medina (1.1.1, 0.1.1, 1.0.1) Large Side Branch Large Myocardium at risk

Dedicated DES in our Future: Need to answer the following Questions What is the unmet clinical need? ‘True’ Bifurcation Lesion SB perfusing large myocardial territories Physician is committed to treatment What are the regulatory barriers? What are the business realities?

Dedicated Bifurcation Stent? Need to answer the following Questions What is the unmet clinical need? Is the clinical need being addressed? Does this makes sense from a business perspective?

Dedicated Bifurcation Stent? Need to answer the following Questions What is the unmet clinical need? Is the clinical need being addressed? What are Clinicians looking for? What are Regulators (FDA) looking for? Does this makes sense* from a business perspective?

What are operators looking for What are operators looking for? The ability to easily/reliably stent the lesion Durable Stent Solution Moving beyond POBA Procedure Ease-of-Use 6 Fr Guide Single Wire Reduce transient closure Reproducible results Long Term Results DES Defined/reduced restenosis

What are operators looking for What are operators looking for? The ability to easily/reliably stent the lesion Baseline Post Procedure Procedural Success Diag Stent: Tryton LAD Stent: Cypher 6 Month F/U No Restenosis High Grade Lesion Mid LAD-Diag Medina (1,1,1) 18

Dedicated Bifurcation Stent? Need to answer the following Questions What is the unmet clinical need? Is the clinical need being addressed? What are Clinicians looking for? What are Regulators (FDA) looking for? Does this makes sense* from a business perspective?

Need for DES Drives Regulatory Pathway Balloon Expandable Self-Expanding Tryton Balloon Delivery System ‘Hybrid’ BMS Tryton + DES Main Vessel Stent Main Vessel Side Branch Cappella Nitinol stent Sheathed Balloon Delivery System ‘Hybrid’ BMS Cappella + DES Main Vessel Stent Abbott BSC Medtronic, Cordis TriReme Minvasys (EU Only) Launching Paciltaxel DES Devax IDE Approved Stentys Self expanding stent in STEMI Developing Paclitaxel DES DES Required

Abbott Vascular/GDT ML FrontierTM Demonstrates DES required for dedicated Main Vessel-Bifurcation Stents Stent Characteristics: BMS (18 mm) Delivery System (7Fr) Single Tip Delivery to avoid wire wrap Simultaneous inflation Provisional Dynamic Frontier Stent Registry N = 105 Angiographic Follow-up (80%) @ 180 days BAR (Combined) = 44.8% MB (in seg) = 29.9%, SB = 29.1% Lefèvre T, et al. J Am Coll Cardiol 2005;46:592–8

TrytonFirst-In-Man Results Support Hybrid (BMS Tryton + DES) Strategy Superb procedural results, ease-of-use validated 6F guide usage 100% simultaneous kiss Great angiographic results DES-like late loss results in both branches Main Vessel (Proximal): 0.25 ± 0.43 mm Main Vessel (Distal): 0.00 ± 0.31 mm Side Branch: 0.17 ± 0.35 mm 9-month clinical results Low Target Lesion Revascularization (3%) No (0%) side branch failures Tryton Side Branch (BMS) Main Vessel Stent (DES) Onuma et al, Eurointerv 2008;3:546-552 22

TrytonFirst-In-Man Results Support Hybrid (BMS Tryton + DES) Strategy Cumulative incidence (%) Prox main 0.25 ± 0.43 Distal main 0.00 ± 0.31 Side 0.17 ± 0.35 Onuma et al, Eurointerv 2008;3:546-552 LLL (mm) 23 23

Regulatory Perspective Reasonable Safety and Effectiveness Safety driven by clinical end point Main Vessel Stent DES: Increases regulatory concerns Drug:Drug Interactions Side Branch (BMS) + Main Vessel (DES) Stent:Stent Interactions

Dedicated Bifurcation Stent? Need to answer the following Questions What is the unmet clinical need? Is the clinical need being addressed? What are the operators looking for? What are the regulators (FDA) looking for? Does this makes sense* from a business perspective? *Makes sense = Makes $ for investors

Dedicated Bifurcation Stent? Need to answer the following Questions What is the unmet clinical need? Is the clinical need being addressed? What are the operators looking for? What are the regulators (FDA) looking for? Does this makes sense* from a business perspective? Is the need (market) large enough? Investment (time & $) is required? *Makes sense = Makes $ for investors

Is the need (market) large enough? ~20% of all PCI’s Kukreja N, Onuma Y,van Domburg R, Serruys P. ACC ‘08 Bifurcations Treated as % of PCI's Rotterdam (cSearch, tSearch & xSearch) Series “All Comers” Studies % Patients % Lesions Leaders Trial1,2 29.1% 21.6% Nobori 23 17.5% 16.9% xSearch4 22.2% N/A Average 22.9% 19.3% 1. Windecker et al. Lancet 2008; 372: 1163–73 2. Wykrzykowska, EuroPCR ’09 3. Danzi, EuroPCR ‘09 4. Serruys, ACC ‘08

Investment (Time/$) is required? Study Size Drives the equation Main Vessel DES Large Company ABT, BSC, Cordis/JnJ, MDT Canabalizes ‘Workhorse’ DES Sales ‘Start-up’ Company 1st in class + unapporved Drug/Polymer Side Branch BMS + Approved DES More ‘Doable’

Are Large RCT Feasible? Resources & Time BBC-1 N=500 Centers = 21 Recruitment = 3 years Hilldick-Smith TCT ‘08

Yes! A Stent based solution for bifurcation lesions is in our future! Conclusions: What is the unmet clinical need? ‘True’ Bifurcations involving large side branches Is the clinical need being addressed? Early data promising RCT Trials required to address safety & efficacy Does this makes from a business perspective? Large poorly addressed need (Large market opportunity) Accessible with manageable IDE Trial (RCT <750 patients) Yes! A Stent based solution for bifurcation lesions is in our future!

Thank you aaron.v.kaplan@hitchcock.org