Will we ever see a dedicated bifurcated DES
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 AV Kaplan MD 1 Stent for Bifurcation Lesions in our Future?
Aaron V. Kaplan, M. D. Conflict-of -Interests • Founder & Director: Tryton Medical • Research Support: – Abbot Vascular – Medtronic – Boston Scientific – Edwards Lifesciences • Practicing Interventional Cardiologist AV Kaplan MD 2 Stent for Bifurcation Lesions in our Future?
Dedicated Bifurcation Stent? Need to answer the following Questions 1. What is the unmet clinical need? 2. Is the clinical need being addressed? 3. Does this makes sense from a business perspective? AV Kaplan MD 3 Stent for Bifurcation Lesions in our Future?
Dedicated Bifurcation Stent? Need to answer the following Questions 1. What is the unmet clinical need? 2. Is the clinical need being addressed? 3. Does this makes sense from a business perspective? AV Kaplan MD 4 Stent for Bifurcation Lesions in our Future?
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 & BBC 1 Population – Smaller side branches – Only treated ~1/3 of time AV Kaplan MD 5 Stent for Bifurcation Lesions in our Future?
Provisional Stenting Small side branch without apparent disease AV Kaplan MD 6 Stent for Bifurcation Lesions in our Future?
Provisional Stenting? Disease in BOTH main vessel & side branch large AV Kaplan MD 7 Stent for Bifurcation Lesions in our Future?
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 & BBC 1 – Smaller side branches – Only treated ~1/3 of time AV Kaplan MD 8 Stent for Bifurcation Lesions in our Future?
Nordic I 1 Stent is all you need? AV Kaplan MD 9 Stent for Bifurcation Lesions in our Future?
Nordic 1 MV (Provisional) MV + SB • Treatment Strategy – POBA if <TIMI 3 – Stent if TIMI 0 after POBA – SB treatment 32% of pts AV Kaplan MD – Culotte, ‘T’ or Crush – Final Kissing Inflations – Final Kiss in 74% of pts 10 Stent for Bifurcation Lesions in our Future?
Nordic 1 MV (Provisional) MV + SB • Treatment Strategy – POBA if <TIMI 3 – Stent if TIMI 0 after POBA – SB treatment 32% of pts – Culotte, ‘T’ or Crush – Final Kissing Inflations – Final Kiss in 74% of pts • Results – Procedural CPK: 8%+ – MACE* @ 6 mos: 2. 9% – Procedural CPK: 18%+ – MACE @ 6 mos = 3. 4% *Mace definition excludes procedural MI +p = 0. 01 AV Kaplan MD 11 Stent for Bifurcation Lesions in our Future?
Nordic 1 Implies SB with small territories Interventionist comfortable NOT treating Clinically Silent AV Kaplan MD 12 Stent for Bifurcation Lesions in our Future?
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 AV Kaplan MD 13 Stent for Bifurcation Lesions in our Future?
Dedicated DES in our Future: Need to answer the following Questions 1. What is the unmet clinical need? – ‘True’ Bifurcation Lesion – SB perfusing large myocardial territories – Physician is committed to treatment 2. What are the regulatory barriers? 3. What are the business realities? AV Kaplan MD 14 Stent for Bifurcation Lesions in our Future?
Dedicated Bifurcation Stent? Need to answer the following Questions 1. What is the unmet clinical need? 2. Is the clinical need being addressed? 3. Does this makes sense from a business perspective? AV Kaplan MD 15 Stent for Bifurcation Lesions in our Future?
Dedicated Bifurcation Stent? Need to answer the following Questions 1. What is the unmet clinical need? 2. Is the clinical need being addressed? – What are Clinicians looking for? – What are Regulators (FDA) looking for? 3. Does this makes sense* from a business perspective? AV Kaplan MD 16 Stent for Bifurcation Lesions in our Future?
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 AV Kaplan MD 17 Stent for Bifurcation Lesions in our Future?
What are operators looking for? The ability to easily/reliably stent the lesion Baseline Post Procedure 6 Month F/U • High Grade Lesion Procedural Success No Restenosis - Mid LAD-Diag - Medina (1, 1, 1) AV Kaplan MD - Diag Stent: Tryton - LAD Stent: Cypher 18 Stent for Bifurcation Lesions in our Future?
Dedicated Bifurcation Stent? Need to answer the following Questions 1. What is the unmet clinical need? 2. Is the clinical need being addressed? – What are Clinicians looking for? – What are Regulators (FDA) looking for? 3. Does this makes sense* from a business perspective? AV Kaplan MD 19 Stent for Bifurcation Lesions in our Future?
Need for DES Drives Regulatory Pathway Self-Expanding Tryton Cappella • Balloon Delivery System • ‘Hybrid’ BMS Tryton + DES Main Vessel Stent DES Required Main Vessel Side Branch Balloon Expandable • Nitinol stent • Sheathed Balloon Delivery System • ‘Hybrid’ BMS Cappella + DES Main Vessel Stent Devax • Abbott • BSC • Medtronic, Cordis • Tri. Reme • Minvasys (EU Only) • IDE Approved Stentys • Self expanding stent in STEMI • Developing Paclitaxel DES • Launching Paciltaxel DES AV Kaplan MD 20 Stent for Bifurcation Lesions in our Future?
Abbott Vascular/GDT ML Frontier. TM Demonstrates DES required for dedicated Main Vessel-Bifurcation Stents • Stent Characteristics: • Frontier Stent Registry – BMS (18 mm) • Delivery System (7 Fr) – Single Tip Delivery to avoid wire wrap – Simultaneous inflation – Provisional Dynamic – 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 AV Kaplan MD 21 Stent for Bifurcation Lesions in our Future?
Tryton. First-In-Man Results Support Hybrid (BMS Tryton + DES) Strategy • Superb procedural results, ease-of-use validated - 6 F 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 Tryton Side Branch (BMS) • 9 -month clinical results - Low Target Lesion Revascularization (3%) - No (0%) side branch failures Onuma et al, Eurointerv 2008; 3: 546 -552 Main Vessel Stent (DES) AV Kaplan MD 22 Stent for Bifurcation Lesions in our Future?
Tryton. First-In-Man Results Support Hybrid (BMS Tryton + DES) Strategy 100 90 80 70 60 ulative incidence 50 (%) Prox main 0. 25 ± 0. 43 40 Distal main 0. 00 ± 0. 31 30 Side 0. 17 ± 0. 35 20 10 0 (1. 0) (0. 5) Onuma et al, Eurointerv 2008; 3: 546 -552 AV Kaplan MD 0. 0 0. 5 1. 0 1. 5 2. 0 LLL (mm) 23 Stent for Bifurcation Lesions in our Future?
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 AV Kaplan MD 24 Stent for Bifurcation Lesions in our Future?
Dedicated Bifurcation Stent? Need to answer the following Questions 1. What is the unmet clinical need? 2. Is the clinical need being addressed? – What are the operators looking for? – What are the regulators (FDA) looking for? 3. Does this makes sense* from a business perspective? *Makes sense = Makes $ for investors AV Kaplan MD 25 Stent for Bifurcation Lesions in our Future?
Dedicated Bifurcation Stent? Need to answer the following Questions 1. What is the unmet clinical need? 2. Is the clinical need being addressed? – What are the operators looking for? – What are the regulators (FDA) looking for? 3. Does this makes sense* from a business perspective? – Is the need (market) large enough? – Investment (time & $) is required? *Makes sense = Makes $ for investors AV Kaplan MD 26 Stent for Bifurcation Lesions in our Future?
Is the need (market) large enough? ~20% of all PCI’s Bifurcations Treated as % of PCI's Rotterdam (c. Search, t. Search & x. Search) Series 25% 22% 20% 16% 15% 10% 8% 5% “All Comers” Studies 0% BMS (2002) Cypher (2002) Taxus (2003) Xience (2007) Kukreja N, Onuma Y, van Domburg R, Serruys P. ACC ‘ 08 % Patients % Lesions Leaders Trial 1, 2 29. 1% 21. 6% Nobori 23 17. 5% 16. 9% x. Search 4 22. 2% N/A Average 22. 9% 19. 3% 1. Windecker et al. Lancet 2008; 372: 1163– 73 2. Wykrzykowska, Euro. PCR ’ 09 3. Danzi, Euro. PCR ‘ 09 4. Serruys, ACC ‘ 08 AV Kaplan MD 27 Stent for Bifurcation Lesions in our Future?
Investment (Time/$) is required? Study Size Drives the equation • Main Vessel DES – Large Company ABT, BSC, Cordis/Jn. J, MDT • Canabalizes ‘Workhorse’ DES Sales – ‘Start-up’ Company • 1 st in class + unapporved Drug/Polymer • Side Branch BMS + Approved DES – More ‘Doable’ AV Kaplan MD 28 Stent for Bifurcation Lesions in our Future?
Are Large RCT Feasible? BBC-1 Resources & Time N=500 Centers = 21 Recruitment = 3 years Hilldick-Smith TCT ‘ 08 AV Kaplan MD 29 Stent for Bifurcation Lesions in our Future?
Conclusions: 1. What is the unmet clinical need? – ‘True’ Bifurcations involving large side branches 2. Is the clinical need being addressed? – – Early data promising RCT Trials required to address safety & efficacy 3. 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! AV Kaplan MD 30 Stent for Bifurcation Lesions in our Future?
Thank you aaron. v. kaplan@hitchcock. org AV Kaplan MD 31 Stent for Bifurcation Lesions in our Future?
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