Advances in StentTherapy for Ischaemic Heart Disease

Advances in Stent Therapy for
Ischaemic Heart Disease
Koon-Hou Mak
MD, FRCP, FACC
Consultant Cardiologist
Gleneagles Medical Centre
Singapore
Mak Heart
Advanced Biotechnology
3-Component System
Drug carrier
Drug carrier
vehicle
vehicle
Pharmacologic
Pharmacologic
agent
agent
Stent
Stent
Design
Design
Drug
Drug
-
-
eluting
eluting
Stent
Stent
Mak Heart

Stent Platform
Optimal Geometry
“Closed Cell”
“Open Cell”
0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1.0
Mak Heart
Stent-based Drug Delivery
Cordis
GuidantCook
Boston Scientific BiodiYsio Matrix LO
++++++
+
BiodiYsio Matrix HI JoMed
Sorin BionsensorsConor Medsytems Igaki-Tamai
Mak Heart
Pharmacologic Approaches
Anti-inflammatory
Immunomodulators
Anti-proliferative
Migration inhibitors

ECM-modulators
Promote healing and
reendothelisation
Dexamethasone
M-prednisolone
Interferon γ-=1b
Leflunomide
Sirolimus (& analogs)
Tacrolimus
Mycophenolic acid
Mizoribine
Cyclosporine
Tranilast
Biorest
QP-2, Taxol
Actinomycin
Methothrexate
Angiopeptin
Vincristine
Mitomycine
Statins
C-myc antisense
Sirolimus (& analogs)
RestenASE
2-chloro-
deoxyadenosine
PCNA Ribozyme
Batimastat
Prolyl hydroxylase
inhibitors

Halofuginone
C-proteinase
inhibitors
Probucol
BCP671
VEGF
Estradiols
NO donors
EPC antibodies
Biorest
Advanced coatings
Many agents have
multiple actions
Mak Heart
SIRIUS Analysis
3-year Clinical Outcome
Sirolimus
Sirolimus
Control
Control
P
P
-
-
value
value
(n=533)
(n=533)
(n=525)
(n=525)

Death
Death
3.9% (21)
3.9% (21)
2.9% (15)
2.9% (15)
0.4
0.4
All myocardial infarction
All myocardial infarction
4.1% (22)
4.1% (22)
4.4% (23)
4.4% (23)
0.9
0.9
Q
Q
-
-
wave
wave
1.3% (7)
1.3% (7)
0.6% (3)
0.6% (3)
0.3
0.3
Non
Non

-
-
Q
Q
-
-
wave
wave
2.8% (15)
2.8% (15)
3.8% (20)
3.8% (20)
0.4
0.4
TLR (all)
TLR (all)
6.8% (36)
6.8% (36)
23.2% (122)
23.2% (122)
<0.0001
<0.0001
TVR (all)
TVR (all)
11.6% (62)
11.6% (62)
27.2% (143)
27.2% (143)
<0.0001
<0.0001

TVR (non
TVR (non
-
-
TLR)
TLR)
7.1% (38)
7.1% (38)
9.3% (49)
9.3% (49)
0.2
0.2
MACE
MACE
12.6% (67)
12.6% (67)
27.4% (144)
27.4% (144)
<0.0001
<0.0001
TVF (1
TVF (1
°
°
endpoint)
endpoint)
15.6% (83)
15.6% (83)
30.1% (158)
30.1% (158)

<0.0001
<0.0001
Mak Heart
SIRIUS Analysis
3-year Clinical Outcome
Sirolimus
Sirolimus
Control
Control
P
P
-
-
value
value
(n=533)
(n=533)
(n=525)
(n=525)
Death
Death
3.9% (21)
3.9% (21)
2.9% (15)
2.9% (15)
0.4
0.4
All myocardial infarction
All myocardial infarction
4.1% (22)

4.1% (22)
4.4% (23)
4.4% (23)
0.9
0.9
Q
Q
-
-
wave
wave
1.3% (7)
1.3% (7)
0.6% (3)
0.6% (3)
0.3
0.3
Non
Non
-
-
Q
Q
-
-
wave
wave
2.8% (15)
2.8% (15)
3.8% (20)

3.8% (20)
0.4
0.4
TLR (all)
TLR (all)
6.8% (36)
6.8% (36)
23.2% (122)
23.2% (122)
<0.0001
<0.0001
TVR (all)
TVR (all)
11.6% (62)
11.6% (62)
27.2% (143)
27.2% (143)
<0.0001
<0.0001
TVR (non
TVR (non
-
-
TLR)
TLR)
7.1% (38)
7.1% (38)
9.3% (49)
9.3% (49)
0.2

0.2
MACE
MACE
12.6% (67)
12.6% (67)
27.4% (144)
27.4% (144)
<0.0001
<0.0001
TVF (1
TVF (1
°
°
endpoint)
endpoint)
15.6% (83)
15.6% (83)
30.1% (158)
30.1% (158)
<0.0001
<0.0001
Mak Heart
SIRIUS Analysis
3-year Freedom from TLR
0 90 180 270 360 450 540 630
720
70
75
80
85

90
95
100
Control
(n=525)
Cypher
(n=533)
Days since index procedure
Freedom from TLR
810 900 990 1080
92.9%
92.9%
76.0%
76.0%
P<0.001
∆16.9%
Mak Heart
TAXUS II, IV, V, VI Group Analysis
TAXUS II, IV, V, VI Group Analysis
Freedom from death to 2 years
Freedom from death to 2 years
0 100 200 300 400 500 600 700
800
70
75
80
85
90
95
100

Control
(n=1727)
TAXUS
(n=1718)
Days since index procedure
Percentage
97.6%
97.6%
97.7%
97.7%
P=0.73
Mak Heart
TAXUS II, IV, V, VI Group Analysis
TAXUS II, IV, V, VI Group Analysis
Freedom from MI to 2 years
Freedom from MI to 2 years
0 100 200 300 400 500 600 700
800
70
75
80
85
90
95
100
Control
(n=1727)
TAXUS
(n=1718)
Days since index procedure

Percentage
94.2%
94.2%
94.3%
94.3%
P=0.98
Mak Heart
TAXUS II, IV, V, VI Group Analysis
TAXUS II, IV, V, VI Group Analysis
Freedom from TLR to 2 years
Freedom from TLR to 2 years
0 100 200 300 400 500 600 700
800
70
75
80
85
90
95
100
Control
(n=1727)
TAXUS
(n=1718)
Days since index procedure
Percentage
P<0.0001
92.2%
92.2%
81.6%

81.6%
Mak Heart
TAXUS II, IV, V, VI Group Analysis
TAXUS II, IV, V, VI Group Analysis
Freedom from TLR, 9 months to 2 years
Freedom from TLR, 9 months to 2 years
0 100 200 300 400 500 600 700
800
70
75
80
85
90
95
100
Control
(n=1727)
TAXUS
(n=1718)
Days since index procedure
Percentage
92.2%
92.2%
81.6%
81.6%
94.2%
94.2%
85.2%
85.2%
-

-
2.3%
2.3%
-
-
3.6%
3.6%
P=0.0075
Mak Heart
Primary Endpoint: 8-month Restenosis Rate
9.6
7.0
11.1
8.3
0
2
4
6
8
10
12
In Stent In Segment
P=0.32
P=0.32
P=0.31
P=0.31
Sirolimus (n=684)
Paclitaxel (n=699)
Restenosis Rate (%)
Mak Heart

10.4
5.0
4.7
4.8
1.8
9.2
11.5
5.4
4.6
5.5
1.2
10.6
0
2
4
6
8
10
12
14
MACE Death MI NQWMI TLR TVR
8-month Clinical Event Rate
P=0.41
P=0.41
P=0.54
P=0.54
Sirolimus (n=684)
Paclitaxel (n=699)
Restenosis Rate (%)
P=0.81

P=0.81
P=0.99
P=0.99
P=0.62
P=0.62
P=0.50
P=0.50
Mak Heart
9.2
0.09
-0.07
0.14
0.31
-0.01
-0.1
-0.05
0
0.05
0.1
0.15
0.2
0.25
0.3
0.35
8-month Late Loss (mm)
Sirolimus (n=897)
Paclitaxel (n=852)
Proximal
In-stent
Distal

P<0.001
P<0.001
P<0.001
P<0.001
P<0.001
P<0.001