1. 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

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)
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 :
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)

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
Multiple Stent Report – EM – , Exhibit 1-2 (N=379)
QC02Mar05KLH

5. 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 ,
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.

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

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

8. 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 – , Exhibit 18
QC02Mar05KLH

9. 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 – , Exhibit 6

10. 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 – , Exhibit 9

11. 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

12. 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

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 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
Multistent report Compare – EM
QC02Mar05KLH

15. TLR benefit among Multiple Stent Groups
Control
TAXUS
p=0.0005
p=0.0003
45%
55%
64%
Patients (%)
9 Month Report , 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

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

17. 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

18. 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

19. 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

20. 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