Four Drug Eluting Stent Trials Keith D Dawkins MD FRCP FACC Southampton University Hospital Keith D Dawkins MD FRCP FACC Southampton University Hospital

Four Drug Eluting Stent Trials

Four Drug Eluting Stent Trials

Keith D Dawkins MD FRCP FACCSouthampton University HospitalKeith D Dawkins MD FRCP FACCSouthampton University Hospital

The Trials

• Endeavour I (TCT 2003)Driver + ABT 578 (Medtronic)

• Future II (TCT 2003)S-Stent + Everolimus (Guidant)

• New Sirius (AHA 2003)Bx Velocity + Sirolimus (Cordis/J&J)

• Taxus IV (AHA 2003)Express2 + Paclitaxel (Boston Scientific)

• Endeavour I (TCT 2003)Driver + ABT 578 (Medtronic)

• Future II (TCT 2003)S-Stent + Everolimus (Guidant)

• New Sirius (AHA 2003)Bx Velocity + Sirolimus (Cordis/J&J)

• Taxus IV (AHA 2003)Express2 + Paclitaxel (Boston Scientific)

Endeavour I (Medtronic)

• Safety Study (n=100)• Device

Driver cobalt-chrome stentPC coatingABT 578 : anti-proliferative action blocks mTOR

signal transduction

• Safety Study (n=100)• Device

Driver cobalt-chrome stentPC coatingABT 578 : anti-proliferative action blocks mTOR

signal transduction

Endeavour I (Medtronic)

• Inclusion CriteriaSingle de novo lesionNative coronary arteriesACC/AHA A-B2

Reference vessel diameter 3.0 – 3.5mmLesion length <15mmDiameter stenosis ≥50% - <100%

• Follow-upClinical 1, 4, 9 months, 1- 5 yearsAngio + IVUS 4 and 12 months


Reference vessel diameter 3.0 – 3.5mmLesion length <15mmDiameter stenosis ≥50% - <100%

• Follow-upClinical 1, 4, 9 months, 1- 5 yearsAngio + IVUS 4 and 12 months

Complications

30 Days 12 months

MACE * 1% 2%

Death 0% 0%

MI (all) 1% 1% Q-wave 0% 0%

Non Q-wave 1% 1%

TLR 0% 1%

TVR (non-TL) 0% 0%

Endeavour I (MACE)

*Hierarchical

Endeavour I (QCA 4 months)

0

20

40

60

80

100

Dia

mete

r st

enosi

s (%

)D

iam

ete

r st

enosi

s (%

)

Pre Post 4mPre Post 4m Pre Post 4mPre Post 4m

In-StentIn-Stent In-SegmentIn-Segment

70.3% 70.3%

5.4%

14.4%16.5%

21.7%

Endeavour I (QCA 4 months)

Late loss (mm)

0.11mm 0.09 mm0.33mmProximalProximal DistalDistalIn-

StentIn-Stent

0.2mmIn-

SegmentIn-

Segment

Future II (Guidant)

• RCT (2:1) (n=64)• Device

S-Stent (stainless steel)Bioabsorbable polymer matrixEverolimus : proliferation signal inhibitor, causes

cell cycle arrest in the G1 phase, prevents clonal expansion of activated T-cells

• RCT (2:1) (n=64)• Device

S-Stent (stainless steel)Bioabsorbable polymer matrixEverolimus : proliferation signal inhibitor, causes

cell cycle arrest in the G1 phase, prevents clonal expansion of activated T-cells

Future II (Guidant)


Reference vessel diameter 2.5 – 4.0mmLesion length ≤18mmDiameter stenosis ≥50% - <100%

• Follow-upClinical 1, 6, 12 monthsAngio + IVUS 6 months


Reference vessel diameter 2.5 – 4.0mmLesion length ≤18mmDiameter stenosis ≥50% - <100%


Complications

Everolimusn=21/21

Controln=40/43

MACE * 1 7

Death 0 0

MI (all) 0 1 Q-wave 0 0 Non Q-wave 0 1

TLR 1 6

Future II (MACE 6 months)

*Hierarchical

Future II (QCA 6 months)

0

10

20

30

40

50

Bin

ary

rest

enosi

s (%

)B

inary

rest

enosi

s (%

)

MS EESMS EES


19.4%

30.6%

0.0%

4.8%

MS EESMS EES

p=0.04

p=ns

Future II (QCA 6 months)

0.0

0.2

0.4

0.6

0.8

1.0

1.2

Late

Loss

(m

m)

Late

Loss

(m

m)

EES MSEES MS


0.120.17

0.85

0.54

EES MSEES MS

p=0.002p<0.0001

New Sirius* (Cordis/Johnson & Johnson)

• RCT (1:1) (n= 452)• Device

Bx Velocity stainless steel stentTwo polymers PEVA & PBMASirolimus : proliferation signal inhibitor,

causes cell cycle arrest in the G1 phase, upregulates natural cell cycle inhibitors (p27)

• RCT (1:1) (n= 452)• Device

Bx Velocity stainless steel stentTwo polymers PEVA & PBMASirolimus : proliferation signal inhibitor,

causes cell cycle arrest in the G1 phase, upregulates natural cell cycle inhibitors (p27)

*Combined data from E-Sirius and C-Sirius*Combined data from E-Sirius and C-Sirius

New Sirius* (Cordis/Johnson & Johnson)

• Inclusion CriteriaSingle de novo lesionNative coronary arteriesACC/AHA A-CReference vessel diameter 2.5 - 3.0mmLesion length 15 - 32mmDiameter stenosis ≥50% - 100%




*Combined data from E-Sirius and C-Sirius*Combined data from E-Sirius and C-Sirius

New Sirius (QCA 8 months)

0

10

20

30

40

50

60

Dia

mete

r re

stenosi

s (%

)D

iam

ete

r re

stenosi

s (%

)

Bx CypherBx Cypher


42.7% 44.2%

3.1%5.1%

Bx CypherBx Cypher

p<0.001p<0.001

New Sirius (QCA 8 months)

0

10

20

30

40

50

60

Bin

ary

rest

enosi

s (%

)B

inary

rest

enosi

s (%

)

Bx CypherBx Cypher

In-StentIn-Stent DistalMarginDistalMargin

7.4%

42.3%

2.1%

11.0%

p<0.001p=0.018

ProximalMargin

ProximalMargin

Bx CypherBx Cypher Bx Cypher Bx Cypher

2.0%3.1%

p<0.001

ComplicationsCypher

(%)n=45

Control (%)n=60

p value

RVD (mm) 2.73 2.77 ns

Lesion length (mm) 14.1 14.9 ns

In-Stent late loss (mm)

0.23 1.17 <0.001

Restenosis rate (%)

In-Stent In-Segment

5.410.8

54.556.4

<0.001<0.001

TLR (%) 6.7 30.0 0.003

MACE (%) 11.1 33.3 0.01

New Sirius (Diabetics 12 months)

Taxus IV (Boston Scientific)

• RCT (1:1) (n=1326)• Device

Express2 stainless steel stentTranslute™ elastomeric polymerPaclitaxel : binds tubulin interfering with

microtubular dynamics, inhibits SMC proliferation & migration, ECM synthesis & secretion

• RCT (1:1) (n=1326)• Device

Express2 stainless steel stentTranslute™ elastomeric polymerPaclitaxel : binds tubulin interfering with

microtubular dynamics, inhibits SMC proliferation & migration, ECM synthesis & secretion

Taxus IV (Boston Scientific)


• Follow-upClinical 1, 4, 9 months, 1 – 5 yearsAngio + IVUS 9 months


• Follow-upClinical 1, 4, 9 months, 1 – 5 yearsAngio + IVUS 9 months

TAXUS benefit for TLR sustained

to 12-months

% p

atie

nts

% p

atie

nts

100100

9090

8080

Days since index procedureDays since index procedure

TAXUSTAXUS

ControlControl

0 30 60 90 120 150 180 210 240 270 300 330 365

ΔΔ 9.3% 9.3%P<0.0001P<0.0001

96.8%

87.5%

ΔΔ 10.7% 10.7%P<0.0001P<0.0001

95.6%

84.9%

Taxus IV: Target lesion revascularisation

0

10

20

30

40

<12 12-15 >15 <12 12-15 >15

TL

R a

t 12

mo

nth

s (%

)T

LR

at 1

2 m

on

ths

(%)

Lesion Length (mm)Lesion Length (mm)

ControlControl TAXUSTAXUS

Impact of Vessel Size & Lesion Length

> 3.0

2.5-3.0

< 2.5

RVD (mm

)

RVD (mm

)

Taxus IV: Impact of vessel size & lesion length

16.7

19.6

13.1

5.97.1

3.4

0

10

20

30

No Diabetes Diabetes Diabetes - insulin

Control (n=652) TAXUS (n=662)

Impact of Diabetes Mellitus

N=489 N=507 N=163 N=155 N=54 N=51

P<0.0001 P=0.12P=0.0016

Taxus IV: Impact of DiabetesTLR

at

12

mon

ths

(%)

No DiabetesNo Diabetes DiabetesDiabetes Diabetes (Insulin)Diabetes (Insulin)

Conclusions

• Four effective drugs at reducing restenosis

• Stent delivery system is critical in optimising drug placement

• All four devices/drugs are safe (12 months)

• The ‘ideal’ late loss is yet to be determined (viz. no restenosis vs. minimal restenosis)

• Cost will be a major factor in selecting a particular product

• Four effective drugs at reducing restenosis

• Stent delivery system is critical in optimising drug placement

• All four devices/drugs are safe (12 months)

• The ‘ideal’ late loss is yet to be determined (viz. no restenosis vs. minimal restenosis)

• Cost will be a major factor in selecting a particular product

Documents

Four Drug Eluting Stent Trials Keith D Dawkins MD FRCP FACC Southampton University Hospital Keith D Dawkins MD FRCP FACC Southampton University Hospital