Post on 17-Dec-2015
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
• 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
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)
• Inclusion CriteriaSingle de novo lesionNative coronary arteriesACC/AHA A-B2
Reference vessel diameter 2.5 – 4.0mmLesion length ≤18mmDiameter stenosis ≥50% - <100%
• Follow-upClinical 1, 6, 12 monthsAngio + IVUS 6 months
• Inclusion CriteriaSingle de novo lesionNative coronary arteriesACC/AHA A-B2
Reference vessel diameter 2.5 – 4.0mmLesion length ≤18mmDiameter stenosis ≥50% - <100%
• Follow-upClinical 1, 6, 12 monthsAngio + IVUS 6 months
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
In-StentIn-Stent In-SegmentIn-Segment
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
In-StentIn-Stent In-SegmentIn-Segment
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%
• Follow-upClinical 1, 9, 12 monthsAngio + IVUS 8 months
• Inclusion CriteriaSingle de novo lesionNative coronary arteriesACC/AHA A-CReference vessel diameter 2.5 - 3.0mmLesion length 15 - 32mmDiameter stenosis ≥50% - 100%
• Follow-upClinical 1, 9, 12 monthsAngio + IVUS 8 months
*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
In-StentIn-Stent In-SegmentIn-Segment
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)
• Inclusion CriteriaSingle de novo lesionNative coronary arteriesACC/AHA A-CReference vessel diameter 2.5 - 3.0mmLesion length 15 - 32mmDiameter stenosis ≥50% - 100%
• Follow-upClinical 1, 4, 9 months, 1 – 5 yearsAngio + IVUS 9 months
• Inclusion CriteriaSingle de novo lesionNative coronary arteriesACC/AHA A-CReference vessel diameter 2.5 - 3.0mmLesion length 15 - 32mmDiameter stenosis ≥50% - 100%
• 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