New Clinical Trial Data

from the TAXUS Program

Gregg W. Stone, MD
Columbia University Medical Center
Cardiovascular Research Foundation
 Potential Conflict of interest

• Gregg W. Stone
ƒ Consultancy/research support from
Boston Scientific Corp.
 TAXUS Trial Designs

TAXUS II TAXUS IV TAXUS V TAXUS VI

N = 3,445 (n=529) (n=1314) (n=1156) (n=446)
Formulation SR, MR SR SR MR
Stent Platform NIRx Express Express2 Express
Geography Europe US US Europe
Primary
6 month 9 month 9 month 9 month
Endpoint
Long-term F/U 2 years 2 years 9 months 1 year
Angio Core Lab Cardialysis B&WH B&WH B&WH
Angio F/U (%) 97.0 42.5 85.6 93.5
 Baseline Characteristics

TAXUS II TAXUS IV TAXUS V TAXUS VI

N = 3,445 (n=529) (n=1314) (n=1156) (n=446)

Diabetes (%) 14.3 24.2 30.9 19.9

RVD (mm) 2.75±0.46 2.75±0.48 2.69±0.57 2.79±0.48

Lesion Length (mm) 10.5±4.2 13.3±6.3 17.2±9.2 20.6±7.6

Study Stent Length 15.4±3.62 21.62±7.90 28.4±13.1 33.1±10.1

Stent:Lesion Ratio 1.71±0.74 1.84±0.93 1.83±0.78 1.72±0.59

Type C Lesions (%) NE 21.1 37.2 55.6

Multiple Stents (%) 4.5 7.5 38.8 32.8

 Insights from Meta-analysis

Overall Efficacy
TLR and TVR
Late loss and restenosis

Overall Safety
Early and late stent thrombosis
All death, cardiac death, MI

Subgroups
Impact of vessel size
Impact of lesion length
Impact of diabetes
Impact of multiple stents
 Analysis of All Patients, TAXUS II, IV, V, VI

All Patients
(n=3445)

Control TAXUS
(n=1727) (n=1718)
 Baseline Characteristics (QCA)
All Patients, TAXUS II, IV, V, VI

Control TAXUS P Value

(n=1727) (n=1718)
Diabetes (%) 24.0 23.2 0.60

RVD (mm) 2.73 ± 0.51 2.74 ± 0.51 0.84

Lesion Length (mm) 15.1 ± 8.0 15.2 ± 7.9 0.85

Stent:Lesion Length 1.79 ± 0.82 1.80 ± 0.81 0.81

 TLR at 9 Months
All Patients, TAXUS II, IV, V, VI

Control (n=1727) TAXUS (n=1718)

p<0.0001 p=0.49 p<0.0001
Patients (%)

16.3
14.8

8.3
5.8
2.8 3.2

N= 256 100 48 55 281 143

TLR TVR, Non-TLR TVR
 9-Month MACE
All Patients, TAXUS II, IV, V, VI

Control (n=1727) TAXUS (n=1718)

p=0.57 p=0.66 p=0.66 p<0.0001 p<0.0001 p=0.77

Patients (%)

19.7
16.3
11.8
8.3
4.1 3.7
0.9 0.7 0.5 0.6 1.4 1.3

N= 16 12 9 11 70 64 281 143 340 203 25 22

Cardiac Q-Wave Non-Q TVR MACE All Death
Death MI Wave MI
 Late Loss at 6-9 Months
All Patients, TAXUS II, IV, V, VI

Control (n=1727) TAXUS (n=1718)

p<0.0001 p<0.0001
0.89
±0.58
0.67
mm

±0.58
0.41
±0.54 0.31
±0.49

N= 1228 1242 1229 1244

In-Stent Analysis Segment
 % Binary Restenosis at 6-9 Months
All Patients, TAXUS II, IV, V, VI

Control (n=1727) TAXUS (n=1718)

p<0.0001 p<0.0001

29.9
Patients (%)

27.5

12.3
8.4

338/1227 105/1247 368/1229 154/1249

In-Stent Analysis Segment
 % In-Stent Net Volume Obstruction
All Patients, TAXUS II, IV, V, VI

Control TAXUS
p<0.0001

26.88
±16.80
%

10.32
±11.18

N=518 N=522
 Stent Thrombosis to 2-Years
All Patients, TAXUS II, IV, V, VI

99.3% (C)
Freedom from Stent Thrombosis

100%

98.8% (T)

p=0.44
95%
Control TAXUS
N = 1727 N = 1718

92.5%
0 100 200 300 400 500 600 700 800

Days Since Index Procedure

 Stent Thrombosis to 6 Months
All Patients, TAXUS II, IV, V, VI

99.4% (T)
Freedom from Stent Thrombosis

100%

99.3% (C)

p=0.68
95%

Control TAXUS
N = 1727 N = 1718

92.5%
0 100 200

Days Since Index Procedure

 Stent Thrombosis after 6 Months
All Patients, TAXUS II, IV, V, VI

99.3% (C)
Freedom from Stent Thrombosis

100%

98.8% (T)

p=0.014
95%

Control TAXUS
N = 1727 N = 1718

92.5%
200 300 400 500 600 700

Days Since Index Procedure

 Freedom from Any Death to 2-Years
All Patients, TAXUS II, IV, V, VI

97.6% (C)
100%
Freedom from Any Death

95%
97.7% (T)
90%

85%
p=0.73

80% Control TAXUS

N = 1727 N = 1718
75%

70%
0 100 200 300 400 500 600 700 800

Days Since Index Procedure

 Freedom from MI to 2-Years
All Patients, TAXUS II, IV, V, VI

100%
94.3% (C)
95%
Freedom from MI

90%
94.2% (T)

85% p=0.98
80% Control TAXUS
N = 1727 N = 1718
75%

70%
0 100 200 300 400 500 600 700 800

Days Since Index Procedure

 Freedom from TLR to 2-Years
All Patients, TAXUS II, IV, V, VI

100%
92.2% (T)
95%
Freedom from TLR

90%

85%

80%
81.6% (C)
75% Control TAXUS
N = 1727 N = 1718
p<0.0001
70%
0 100 200 300 400 500 600 700 800

Days Since Index Procedure

 TLR Between 9-Months to 2-years
All Patients, TAXUS II, IV, V, VI

100%
94.2%% (T) Δ=
95%
-2.0% 92.2% (T)
Freedom from TLR

90%

85%
85.2% (C)
80% Δ=
-3.6% 81.6% (C)
75%
284 Days to 2 Years; p=0.0075
70%
0 100 200 300 400 500 600 700 800

Days Since Index Procedure

 Patient Subgroups in Meta-Analysis

Impact of Vessel Size

RVD ≤2.5mm, 2.5mm - ≤3.0mm, >3.0mm

Impact of Lesion Length

Lesion Length <18.0mm, ≥18 - ≤26mm, >26mm

Impact of Diabetic Status

Non-Diabetic, Diabetes treated with Oral Agents,
Diabetes treated with Insulin

Impact of Multiple Stents

Single vs. Multiple Stents
 Vessel Size Subgroups (by QCA)
TAXUS II, IV, V, VI MetaAnalysis

RVD ≤ 2.5mm Control TAXUS

(n=1166) (n=588) (n=578)

RVD 2.5 - ≤ 3.0mm Control TAXUS

All Patients
(n=1249) (n=633) (n=616)

RVD > 3.0mm Control TAXUS

(n=998) (n=491) (n=507)
 Effect of Vessel Size on 9-Month TLR
TAXUS II, IV, V, VI MetaAnalysis

Control TAXUS

p<0.0001 p<0.0001 p=0.0001

Patients (%)

20.7 60% 57% 66%

13.1
8.3 9.8
5.7
3.4

122/588 48/578 83/633 35/616 48/491 17/507

RVD ≤ 2.5mm RVD 2.5 ≤ 3.0mm RVD > 3.0 mm

 Effect of Vessel Size on 9m QCA
In-Segment, TAXUS II, IV, V, VI MetaAnalysis

Control TAXUS

p<0.0001 p<0.0001 p<0.0001 p<0.0001 p<0.0001 p<0.0001

0.73 42.4
0.63 0.64 ±0.62
±0.53 ±0.57 28.3
0.30 0.33 0.30 19.5
±0.54 18
±0.50 ±0.44
10.6
6.3

408 430 452 432 361 374 173 84 128 46 65 24

≤2.5 2.5≤3.0 >3.0 ≤2.5 2.5≤3.0 >3.0
Late Loss Binary Restenosis
 Lesion Length Subgroups (by QCA)
TAXUS II, IV, V, VI MetaAnalysis

Lesions <18mm Control TAXUS

(n=2450) (n=1238) (n=1212)

Lesions 18-26mm Control TAXUS

All Patients
(n=635) (n=324) (n=311)

Lesions >26mm Control TAXUS

(n=328) (n=154) (n=174)
 Effect of Lesion Length on 9-Month TLR
TAXUS II, IV, V, VI MetaAnalysis

Control TAXUS

p<0.0001 p<0.0001 p=0.0040

Patients (%)

22.1
60% 65% 53%
15.7
13.6
10.3
5.4 5.5

168/1238 65/1212 51/324 17/311 34/154 18/174

<18 mm ≥18 mm - ≤26 mm >26 mm

 Effect of Lesion Length on 9m QCA
In-Segment, TAXUS II, IV, V, VI MetaAnalysis

Control TAXUS

p<0.0001 p<0.0001 p<0.0001 p<0.0001 p<0.0001 p<0.0001

51.2
0.82
0.64 0.67 ±0.65
37.1
±0.56 ±0.59
0.31 0.35 24.7
0.31
±0.48 ±0.53 ±0.52 17.5 16.3
10.2

851 850 251 239 125 146 210 87 93 42 64 24

<18 ≥18 ≤26 >26 <18 ≥18 ≤26 >26
Late Loss Binary Restenosis
 Effect of Vessel Size and Lesion Length on
9m TLR (All Patients, TAXUS II, IV, V, VI)

RVD in terciles (mm)

40 Control TAXUS
Patients 9m TLR (%)

35
30
25
20
15
10
5 ≤2.48
>2.49<2.95
0 ≥2.9
.7 . 6 6 .7 . 6 . 6
0 1 6 6. 0 1 6 6
<1 7 ≤ ≥1 <1 7 ≤ ≥ 1
0. 0.
≥1 ≥1
Lesion Length in terciles (mm)
 Diabetic Subgroups
TAXUS II, IV, V, VI MetaAnalysis

Oral Agents (n=558)

Diabetic Control TAXUS

(n=279) (n=279)
(n=814)

Insulin Requiring (n=256)

All Patients
(n=3445) Control TAXUS
(n=136) (n=120)
Non-Diabetic
(n=2631)
Control TAXUS
(n=1312) (n=1319)
 Effect of Diabetic Status on 9-Month TLR
TAXUS II, IV, V, VI MetaAnalysis

Control TAXUS
p<0.0001 p=0.0001 p=0.0063
19.4
Patients (%)

16.9
13.6 61% 59% 66%

7.9
5.4 5.8

179/1312 71/1319 54/279 22/279 23/136 7/120

Diabetic Diabetic
Non-Diabetic
(Oral Agents) (Insulin-Requiring)
 Effect of Diabetic Status on 9m QCA
In-Segment, TAXUS II, IV, V, VI MetaAnalysis

Control TAXUS

p<0.0001 p<0.0001 p=0.0012 p<0.0001 p<0.0001 p=0.0001

41.9
0.66 0.69
±0.61
0.65 36.0
±0.57 ±0.55
27.6
0.32
±0.49 0.28 0.22
±0.50 12.1 12.6 14.6
±0.52

950 951 186 206 93 87 262 115 67 26 39 13

Non-Diab. Oral Insulin Non-Diab. Oral Insulin

Late Loss Binary Restenosis
 Single vs. Multiple Stenting Across Trials

TAXUS TAXUS TAXUS TAXUS

II IV V VI

2/529* 8/1314 8/1156 3/446

No Stents
(0.4%) (0.6%) (0.7%) (0.7%)

494/529* 1207/1314 769/1156 270/446

Single Stents
(93.4%) (91.9%) (66.5%) (60.5%)

33/529* 99/1314 379/1156 173/446

Multiple Stents
(6.2%) (7.5%) (32.8%) (38.8%)

* TAXUS II Excludes 7 Confounders

 Multiple Stent Analysis
TAXUS II, IV, V, VI MetaAnalysis

Single Stents Control TAXUS

(n=2740) (n=1378) (n=1362)

All Patients
Multiple Stents Control TAXUS
(n=684) (n=336) (n=348)
 Baseline Characteristics
Single vs. Multiple Stents (pooled), TAXUS II, IV, V, VI

Single Multiple P value

n=2740 n=684

Age 62.0 ± 10.8 62.9 ± 10.5 0.052

Type C lesions 21.9 69.4 <0.0001
Silent Ischemia 19.6 11.1 <0.0001
RVD (mm) 2.74 ± 0.50 2.71 ± 0.53 0.15
Lesion length (mm) 13.0 ± 5.6 23.6 ± 10.1 <0.0001
Stent length (mm) 20.1 ± 6.0 41.7 ± 11.0 <0.0001
Stent:Lesion Ratio 1.73 ± 0.70 2.07 ± 1.12 <0.0001
 30 Day MACE
Single vs. Multiple Stents (pooled), TAXUS II, IV, V, VI

Single Multiple P value

n=2740 n=684

MACE, Overall (%) 3.1 6.3 0.0002

Cardiac Death 0.1 0.3 0.34
MI 2.8 6.0 0.0001
Q-wave 0.3 0.9 0.04
Non Q-wave 2.5 5.1 0.001
TVR 0.4 1.0 0.08
TLR 0.3 0.9 0.10
 9-Month Safety Summary
Single vs. Multiple Stents (pooled), TAXUS II, IV, V, VI

Single (n=2740) Multiple (n=684)

p=1.00 p=0.010 p=0.0025 p<0.0001 p=1.00 p=0.18
Patients (%)

23.2

13.8

6.0
3.3
0.8 0.7 0.4 1.3 1.4 1.3 0.5 1.0

22 5 11 9 91 41 379 159 37 9 15 7
Cardiac Q-Wave Non-Q MACE All Stent
Death MI Wave MI Death Thrombosis
 Effect of Multiple Stenting on Late Loss
In-Segment, TAXUS II, IV, V, VI MetaAnalysis

Control TAXUS

p<0.0001 p<0.0001
0.85
±0.62
0.61
mm

±0.55
0.39
0.29 ±0.55
±0.47

956 954 273 288

Single Stent Multiple Stents

 Effect of Multiple Stenting on Restenosis
In-Segment, TAXUS II, IV, V, VI MetaAnalysis

Control TAXUS

p<0.0001 p<0.0001
52.7
Patients (%)

59% 61%

23.4 20.8
9.7

224/956 93/958 144/273 60/289

Single Stent Multiple Stents

 Effect of Multiple Stenting on 9-Month TLR
TAXUS II, IV, V, VI MetaAnalysis

Control TAXUS
p<0.0001 p<0.0001
25.6
Patients (%)

59% 66%
12.3
8.6
5.0

169/1378 68/1362 86/336 30/348

Single Stent Multiple Stents

 Baseline Characteristics
Single Stent Patients, TAXUS II, IV, V, VI

Control TAXUS P value

n=1378 n=1362

Type C lesions 21.4 22.4 0.57

RVD (mm) 2.74±0.50 2.75±0.50 0.72

Lesion length (mm) 13.0±5.6 13.0±5.6 0.96

Stent length (mm) 20.1±5.9 20.2±6.1 0.60

Stent:Lesion Ratio 1.73±0.71 1.73±0.70 0.84
 30 Day MACE
Single Stent Patients, TAXUS II, IV, V, VI

Control TAXUS P value

n=1378 n=1362

MACE, Overall (%) 3.2 2.9 0.74

Cardiac Death 0.2 0.1 0.62
MI 2.9 2.7 0.82
Q-wave 0.3 0.3 1.00
Non Q-wave 2.6 2.4 0.81
TVR 0.4 0.4 1.00
TLR 0.4 0.3 0.75
 9-Month Safety Summary
Single Stent Patients, TAXUS II, IV, V, VI

Control (n=1378) TAXUS (n=1362)

p=0.83 p=0.38 p=0.14 p<0.0001 p=0.87 p=0.61
Patients (%)

17.2
10.4
3.8 2.8
0.9 0.7 0.3 0.5 1.3 1.4 0.7 0.4
12 10 4 7 53 38 237 142 18 19 9 6
Cardiac Q-Wave Non-Q MACE All Stent
Death MI Wave MI Death Thrombosis
 Baseline Characteristics
Multiple Stent Patients, TAXUS II, IV, V, VI

Control TAXUS P value

n=336 n=348

Type C lesions 70.3 68.7 0.67

RVD (mm) 2.72±0.55 2.71±0.52 0.73

Lesion length (mm) 23.7±10.4 23.6±9.7 0.95

Stent length (mm) 41.6±11.4 41.7±10.7 0.83

Stent:Lesion Ratio 2.07±1.14 2.07±1.11 0.92
Overlap Stents (%) 85.3 81.7 0.30
 30 Day MACE
Multiple Stent Patients, TAXUS II, IV, V, VI

Control TAXUS P value

n=336 n=348

MACE, Overall (%) 4.2 8.3 0.027

Cardiac Death 0.3 0.3 1.00
MI 3.9 8.0 0.024
Q-wave 0.9 0.9 1.00
Non Q-wave 3.0 7.2 0.015
TVR 0.9 1.1 1.00
TLR 0.6 1.1 0.69
 9-Month Safety Summary
Multiple Stent Patients, TAXUS II, IV, V, VI

Control (n=336) TAXUS (n=348)

p=0.68 p=0.75 p=0.11 p=0.0001 p=0.33 p=1.00

29.8
Patients (%)

17.0

7.5
4.5
0.9 0.6 1.5 1.1 1.8 0.9 0.9 1.1

3 2 5 4 15 26 100 59 6 3 3 4
Cardiac Q-Wave Non-Q MACE All Stent
Death MI Wave MI Death Thrombosis
 Freedom from All Death to 2-Years
Multiple Stent Patients, TAXUS II, IV, V, VI

97.6% (T)
100%
Freedom from All Death

95%

90% 96.7% (C)

85%

80%
p=0.34
75%
Control TAXUS
70% N = 336 N = 348
65%

60%
0 100 200 300 400 500 600 700

Days Since Index Procedure

 Freedom from Cardiac Death to 2-Years
Multiple Stent Patients, TAXUS II, IV, V, VI

99.4% (T)
Freedom from Cardiac Death

100%

95%
99.1% (C)
90%

85%

80%
p=0.63
75%

70% Control TAXUS

N = 336 N = 348
65%

60%
0 100 200 300 400 500 600 700

Days Since Index Procedure

 Freedom from MI to 2-Years
Multiple Stent Patients, TAXUS II, IV, V, VI

100%

92.3% (C)
Freedom from MI

95%

90%

85%
89.8% (T)
Control TAXUS
N = 336 N = 348 p=0.19
80%
0 100 200 300 400 500 600 700 800

Days Since Index Procedure

 Freedom from TLR to 2-Years
Multiple Stent Patients, TAXUS II, IV, V, VI

100%
90.9% (T)
95%
Freedom from TLR

90%

85%

80%

75%
p<0.0001
70%

65% Control TAXUS

N = 336 N = 348 69.9% (C)
60%
0 100 200 300 400 500 600 700

Days Since Index Procedure

 Freedom from MACE to 2-Years
Multiple Stent Patients, TAXUS II, IV, V, VI

100%

95% Control TAXUS

Freedom from MACE

N = 336 N = 348
90%

85% 76.8% (T)

80%

75%

70%

65%
p=0.0002
63.5% (C)
60%
0 100 200 300 400 500 600 700

Days Since Index Procedure

 TAXUS Meta-Analysis Conclusions
Overall Efficacy to 2 Years
Marked ⇓ TLR and TVR
Marked ⇓ late loss and restenosis
Overall Safety to 2 Years
No risk of early stent thrombosis
? Increase in late stent thrombosis (n=6)
No increase in death, cardiac death, or MI
Subgroups
Effective at all vessel sizes
Effective at all lesion lengths
Effective in all diabetic classes and non diabetics
Multiple stents: Increase peri-procedural NQMI, with
marked ⇓TLR and restenosis, with similar survival