Jeffrey J. Popma, MD Director, Interventional Cardiology

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

2. 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

3. Multiple Overlap Stenting in TAXUS V All Patients (n=1156) Multiple Stents inTarget Vessel (n=379) Planned Procedures (n=248) Emergent Procedures (n=78) QCA-confirmed Overlapping Stents (n=326) Received no stents (n=8) Single Stents (n=769) Planned Procedures (n=281) Emergent Procedures (n=98) No overlap(n=53) 4. 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

5. MACE in QCA Analysis Subgroup 0.08 8.7% 3.9% MI 0.0027 16.3% 29.8% TVR 1.00 0.5% 0.6% Cardiac Death 0.0172 20.7% 32.0% 9-Month MACE 0.5% 3.3% 0.0% 3.3%Controln=184 0.62 1.6% TVR 0.0457 8.6% MI 0.0% Cardiac Death 0.0457 8.6% 30-Day MACE P value TAXUS n=188 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 ( 70%100%)

• • Branch TIMI flow

7. Side Branch Analysis in Multiple Stenting Sidebranch Occlusion TIMI Flow Reduction Side Branch Narrowing( 70%100%) 8. Main Vessel Analysis in Multiple Stenting Peri-procedural Ischemic Complicatons 0.50 3.2 1.6 Final (%) 1.00 7.4 7.6 Transient (%) No Reflow - 0.0 0.0 Final (%) 0.28 3.2 1.1 Transient (%) TIMI Flow - 0.0 0.0 Final (%) 0.62 1.6 0.5 Transient (%) Abrupt Closure Controln=184 pts P value TAXUS n=188 pts 9. Side Branch Analysis in Multiple Stenting 0.74 89.1 87.5 % pts with Sidebranch 289 268 Total Sidebranches (n) 0.45 1.42 0.371.40 0.36Sidebranch RVD (mm) 0.55 1.66 0.991.60 1.01# Branches (per pt.) Controln=184 pts P value TAXUS n=188 pts 10. Side Branch Analysis in Multiple Stenting TIMI Flow: Timing, Any Time Point Timeline 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 FirstStent 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 11. Impact of the Overlap Region (per side branch) Any Sidebranch Occlusion Any Sidebranch Narrowing Any TIMI Flow Reduction Control TAXUS 37/203 34/207 8/48 15/55 51/203 68/207 12/48 26/55 56/203 58/207 21/48 24/55 Non-overlap region Overlap region Non-overlap region Overlap region Non-overlap region Overlap region p=0.74 p=0.23 p=0.10 p=0.025 p=1.00 p=1.00 12. Non-Q-Wave MI in Multiple Stent Patients: Transient Side Branch Compromise 28.6% 41.9% (65/155) Side Branch (42/147) P=0.0164 MI 3.3% 8.3% 30 Days Taxus N=193 Control N=184 (6/184) (16/193) P=0.0472 1.1% (2/184) Main Branch (6/188) 3.2% P=0.284 3.9% (7/181) (16/191) 8.4% P=0.0858 MI 9 Months 17.7% (25/155) (26/147) 16.1% P=0.760 TIMI Flow Reduction Side Branch 62% decrease 38% decrease Peri-procedure TIMI Flow reduction 13. 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

14. Side Branch Analysis in Multiple Stenting Patients with and without CK-MB>3x ULN Myonecrosis