Bifurcation Disease: Simulation Training Curriculum Sidebranch Occlusion, Restenosis, And Angiographic Challenges Simulation Training Curriculum

Unresolved Bifurcation Issues For Evaluation of New Strategies “True” Bifurcation Disease Sidebranch occlusion with DES bifurcation and its impact on MACE Restenosis Rates: Main Vessel Sidebranch Regional Angiographic Analysis to Evaluate Dedicated Stents

Multiple Classification System

IVUS Predictors of Side Branch Occlusion in Bifurcation Lesions After PCI Ostial lesion location Plaque distribution Furukawa et al . Circ J. 2005; 69(3):325-30.

Unresolved Bifurcation Issues For Evaluation of New Strategies “True” Bifurcation Disease Sidebranch occlusion with DES bifurcation and its impact on MACE Restenosis Rates: Main Vessel Sidebranch Regional Angiographic Analysis to Evaluate Dedicated Stents

Multiple Overlap Stenting in TAXUS V All Patients (n=1156) Received no stents (n=8) Single Stents (n=769) Planned Procedures (n=281) Multiple Stents in Target Vessel (n=379) Emergent Procedures (n=98) No overlap (n=53) What happened to those other 53 patients? - There are 326 patients in the database with overlap. Of these 326 patients, 324 do not have gap, and 2 have gap. - There are 53 patients in the database without overlap. Of these 53 patients, 45 do not have gap, and 8 have gap. - There are 10 patients (2+8) that have gap, and 369 patients (324+45) that do not have gap. TAXUS V 9 Month Report 2005-02-14: Multiple (N=379): Exhibit 93 Single (N=769): Exhibit 101 Overlap (N=326): Exhibit 96 Planned Overlap (N=248): Exhibit 97 Unplanned Overlap (N=78): Exhibit 98 Planned Multiple: Exhibit 94 Unplanned Multiple: Exhibit 95 Planned Procedures (n=248) QCA-confirmed Overlapping Stents (n=326) Emergent Procedures (n=78)

Objective: Multiple Stent Analysis TAXUS V Multiple Stent Patients: 62.7% Lesions >26mm 86.0% QCA-confirmed overlapping stents 44.0% 2.25 and 2.5 mm stents 34.3% Patients with diabetes 73.1% Type C lesions Multiple Stent Report – EM – 2005-02-28, Exhibit 1-2 (N=379) QC02Mar05KLH

MACE in QCA Analysis Subgroup Control n=184 TAXUS n=188 P value 30-Day MACE 3.3% 8.6% 0.0457 Cardiac Death 0.0% MI TVR 0.5% 1.6% 0.62 9-Month MACE 32.0% 20.7% 0.0172 0.6% 1.00 3.9% 8.7% 0.08 29.8% 16.3% 0.0027 9 Month Report 2005-02-14, Clinical Procedural Success: Exhibit 1 PCI in non-targ. vessel: Exhibit 1, pg. 2 GP inhibitors during procedure: Exhibit 14 Maximum Inflation Pressure: Exhibit 6, line 2 (confirm that this is correct variable to report) Max. Balloon:Artery Ratio: Exhibit 6, line 4 IVUS: Exhibit 6, Pg. 1, line 6.

TAXUS V Multiple Stent Analysis Methodology Blinded core lab analysis of all multiple stent patients Main Vessel Analysis: Main vessel No Reflow, TIMI flow, Dissection, Distal Embolization, Abrupt Closure Side Branch Analysis (for branches >1 mm): Branch occlusion (total occlusion) Branch narrowing (Δ≥70%  100%) Branch TIMI flow

Side Branch Analysis in Multiple Stenting Control n=184 pts TAXUS n=188 pts P value Total Sidebranches (n) 268 289 % pts with Sidebranch 87.5 89.1 0.74 # Branches (per pt.) 1.60±1.01 1.66±0.99 0.55 Sidebranch RVD (mm) 1.40±0.36 1.42±0.37 0.45 Multiple Stent Report – EM – 2005-02-25, Exhibit 6

Side Branch Analysis in Multiple Stenting Sidebranch Occlusion Side Branch Narrowing (Δ ≥ 70%  100%) TIMI Flow Reduction

Impact of the Overlap Region (per side branch) Control TAXUS Any Sidebranch Occlusion Any Sidebranch Narrowing Any TIMI Flow Reduction p=0.74 p=0.23 p=1.00 p=0.10 p=0.025 37/203 34/207 8/48 15/55 56/203 58/207 21/48 24/55 51/203 68/207 12/48 26/55 Non-overlap region Overlap Non-overlap region Overlap Non-overlap region Overlap

SIRIUS. C-SIRIUS, E-SIRIUS, DIRECT N = 1735 Single Stent N = 1076 No Stent N = 3 Multiple Stents in Target Vessel N=656 Multiple Long Stents in ≥ 2 stents with each stent ≥ 18 mm in each target vessel (N=271) QCA Not Available (N=38) Multiple Long Stent QCA Analysis (N=233) BMS (N=94) SES (N=133)

Impact of the Overlap Region (per side branch) 11/189 16/145 0/19 1/8 27/189 28/145 2/19 2/8 17/173 18/140 4/15 2/7 Side Branch Occlusion Side Branch Narrowing TIMI Flow Reduction

Side Branch Analysis in Multiple Stenting Patients with and without CK-MB>3x ULN + Myonecrosis n=106 branches no Myonecrosis n=451 branches P Value Occlusion 35.6 % 9.9 % <0.0001 Narrowing 41.3 % 20.5 % ↓ Branch TIMI Flow 42.3 % 20.0 % Myonecrosis Multistent analysis 20050228 Multistent report Compare – EM- 2005-03-02 QC02Mar05KLH

Sidebranch Occlusions Sidebranch occurs more often in regions of stent overlap with both CYPHER and TAXUS Although the many sidebranches that occlude are small (1.4 mm), SBO is associated with periprocedural CK MB elevations Reduced TIMI flow is associated with myonecrosis Newer stent designs should minimize the degree of overlap in regions important sidebranch

Unresolved Bifurcation Issues For Evaluation of New Strategies “True” Bifurcation Disease Sidebranch occlusion with DES bifurcation and its impact on MACE Restenosis Rates with BMS and DES: Main Vessel Sidebranch Regional Angiographic Analysis to Evaluate Dedicated Stents

One Stent is Preferred With Bare Metal Stents Yamashita et al JACC 2000; 35:1145

One Stent is Preferred One Stent Two Stents Intracoronary Stent Implantation for True Bifurcation Lesion Suwaidi et al JACC 2000;35:929

DES Bifurcation Approaches Author n Stent Type RR (%) PB (%) SB (%) TLR MACE Colombo et al MV Only 22 Cypher 18.7 4.8 14.2 4.5 13.6 Circ 2004; 109:1244 Both 63 28 5.7 21.8 9.5 19 Ge et al 57 5.4 AJC 2005; 95:757 117 23 9.6 13.5 8.9 13.3 Hoye et al Crush 130 36.4 9.3 27.1 6.2 12.3 JACC 2006; 47:1949 101 Taxus 31.6 22.8 14.5 Moussa et al * 120 --- 11.3 13.0 AJC 2006; 97:1317 *Restenosis was focal in all patients and localized at the sidebranch ostium in 69% of patients

Importance of Final Kissing Ballon Post-Dilatation No Kiss Final Kiss Importance of Final Kissing Ballon Post-Dilatation Ge et al J Am Coll Cardiol. 2005 Aug 16;46(4):613-20.

Unresolved Bifurcation Issues For Evaluation of New Strategies “True” Bifurcation Disease Sidebranch occlusion with DES bifurcation and its impact on MACE Restenosis Rates: Main Vessel Sidebranch Regional Angiographic Analysis to Evaluate Dedicated Stents

Ostial – Follow-up branch vessel

QCA Challenges: Determining Precise Regional Changes for Bifurcated Stents Prox RVD Distal RVD Branch RVD 5 mm Ostium

Setting the Stage: Conclusions Current bifurcation stent strategies are insufficient to provide safe and predictable long term results – and they are a lot of work With the evaluation of new technologies: - Dedicated or sidebranch salvage techniques - Periprocedural MI  preservation of large and small branch flow - Regional restenosis rates and failure analysis – angiographic follow-up will be essential but may lead to oculostenotic TLR