TAXUS – Myonecrosis and sidebranch patency concerns are short-term issues with no long-term consequences, and the benefits are undeniable Jeffrey J. Popma, MD Director, Interventional Cardiology Brigham and Women’s Hospital Associate Professor of Medicine Harvard Medical School Boston, MA

New Insights into Periprocedural MI, Multiple Stents and Sidebranches Distal platelet embolization was felt to be a major component of myonecrosis during PCI. GPIIb-IIIa inhibitors reduced this risk Differential cardiac enzyme elevation was noted in the Taxus 5 Trial in patients treated with multiple stents, leading to a re-examination of the root cause of this event

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

Main Vessel Analysis in Multiple Stenting Peri-procedural Ischemic Complicatons Control n=184 pts TAXUS n=188 pts P value No Reflow Transient (%) 7.6 7.4 1.00 Final (%) 1.6 3.2 0.50 TIMI Flow 1.1 0.28 0.0 - Abrupt Closure 0.5 0.62 Multiple Stent Report – EM – 2005-02-28, Exhibit 18 QC02Mar05KLH

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 TIMI Flow: Timing, Any Time Point Control (n=263) TAXUS (n=285) Baseline 1.5% 2.5% p=0.55 After Pre- Dilatation 3.8% 6.3% p=0.24 After First Stent 10.3% 15.1% p=0.10 After Additional Stent(s) 12.9% 20.7% p=0.02 After Post- Dilatation 12.9% 22.1% p=0.05 Timeline Multiple Stent Report – EM – 2005-02-25, Exhibit 9

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

TIMI Flow Reduction Side Branch Non-Q-Wave MI in Multiple Stent Patients: Transient Side Branch Compromise Peri-procedure TIMI Flow reduction Control N=184 MI TIMI Flow Reduction Side Branch MI Main Branch Side Branch 28.6% 38% decrease 17.7% 3.3% 3.9% 1.1% (6/184) (2/184) (42/147) (26/147) (7/181) P=0.0472 P=0.284 P=0.0164 P=0.760 P=0.0858 Taxus N=193 41.9% 62% decrease 16.1% 8.3% 8.4% 3.2% (16/193) (25/155) (16/191) (6/188) (65/155) 30 Days 9 Months

Possible Causes of Sidebranch Compromise Likely related to geometric narrowing from increased strut thickness Less likely related to Polymer webbing and/or clumping Platelet and/or thrombus deposition Paclitaxel-induced spasm

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

TLR benefit among Multiple Stent Groups Control TAXUS p=0.0005 p=0.0003 45% 55% 64% Patients (%) 9 Month Report 2005-02-14, Exhibit 1, Exhibit 93, 97 QC02Mar05KLH 34/123 89/567 51/181 12/121 48/560 24/191 Multiple Stents Multiple Overlapping stents All patients

What Are The Predictors of Late Mortality? Jeremias et al JACC 2004:44:1210-4

Mortality Risk Confined to Those with Procedural Failure Unsuccessful Procedure = > 50% residual stenosis, TIMI <3, Final Dissection > C; SAT, Urgent TVR < 24 hours Jeremias et al JACC 2004:44:1210-4

Multiple Stent Patients: Early Non-Q-Wave MI is not Associated with Long-Term Sequelae; Taxus Benefits Persist 8.3% (16/193) MI 3.3% 30 Days (6/184) P=0.0472 1.1% 0.6% 7.4% (2/189) (14/180) 12 Months 3.9% (7/180) MI Cardiac Death (1/180) P=0.0852 P=0.284 14.3% (27/189) 12 Months (57/180) 31.7% P=0.0001 TLR Control N=184 Taxus N=193

Freedom from Cardiac Death to 2-Years Multiple Stent Patients, TAXUS II, IV, V, VI 100% 95% 90% 85% 80% 75% 70% 65% 60% 99.1% (C) p=0.63 Freedom from Cardiac Death TAXUS N = 348 Control N = 336 100 200 300 400 500 600 700 Days Since Index Procedure

Conclusions There was slightly higher Non QWMI rate in patients treated with multiple TAXUS stents in the TAXUS 5 trial due to sidebranch reduction in flow in the region of stent overlap The sidebranch flow returned toward baseline at 9 month follow-up There was a 64% reduction in TLR in patients treated with multiple overlapping stents No late mortality differences up to 2 years in patients treat with multiple stents in a TAXUS meta analysis