The Detrimental Impact of Chronic Renal Insufficiency

1
Long-Term Clinical Benefit of CYPHER
Sirolimus-Eluting Coronary Stents Five-Year
Follow-Up of the SIRIUS Study Martin B. Leon,
Jeffrey W. Moses, David R. Holmes, Jr., Dean J.
Kereiakes, Donald Cutlip, Sidney A. Cohen, and
Richard E. Kuntz Columbia University Medical
Center, NYC
American College of Cardiology Annual Scientific
Sessions 2007 March 24-27 , New Orleans, LA
2
SIRIUS 5 Year Follow-upConflicts of Interest
M.B. Leon, Cordis, JohnsonJohnson J.W. Moses,
Cordis, JohnsonJohnson D.R. Holmes, None D.J.
Kereiakes, None D. Cutlip, None S.A. Cohen,
Cordis Employee, Group Director Clinical
Research R.E. Kuntz, None
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SIRIUS Background Purpose

• BACKGROUND The randomized blinded SIRIUS trial,
  comparing sirolimus-eluting stents (SES) with
  bare metal stent controls, clearly demonstrated
  at 8-9 mos FU, a dramatic improvement in
  angiographic late loss and restenosis, IVUS
  intimal hyperplasia, and clinical endpoints (TLR,
  TVR, MACE, and TVF) after SES. The long-term
  durability of SES clinical outcomes remains
  poorly understood.
• PURPOSE To determine after 5-years clinical F/U
  if the safety (death, MI, and stent thrombosis)
  and efficacy (TLR and TVR) of SES compared with
  controls are maintained.

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SIRIUS - Study Design
Control Bx VELOCITYTM n 525
n 1058 patients
De Novo Coronary Lesions Diameter 2.5-3.5
mm Length 15-30 mm
Sirolimus-eluting Bx VELOCITYTM n 533
Primary Endpoint target vessel failure (TVF)
cardiac death, MI or TVR (FU at 9 mos)
Angiographic Substudy first 850 pts (FU at 8
mos) IVUS Substudy 250 pts at selected sites
(FU at 8 mos)
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SIRIUS - Patient Demographics
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SIRIUS - Baseline Lesion and Angiographic
Characteristics
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SIRIUS - Clinical Events _at_ 9 mos
8
SIRIUS Patient Flow (Clinical)
Study population(n1,058)
Control(n525)
Sirolimus(n533)
1-year follow-up(n1,051 99.3)
Control(n522)
Sirolimus(n529)
2-year follow-up(n1,045 98.7)
Control(n520)
Sirolimus(n525)
3-year follow-up(n1,036 97.9)
Control(n516)
Sirolimus(n520)
4-year follow-up(n1,025 96.8)
Control(n509)
Sirolimus(n516)
5-year follow-up(n992 93.8)
Control(n491)
Sirolimus(n501)
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SIRIUS - Clinical Events _at_ 5 yrs
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SIRIUS Clinical Events _at_ 5 yrs
Major Adverse Cardiac Events
P0.21
P1.00
Plt0.0001
Plt0.0001
P0.90
Plt0.0001
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SIRIUS Survival Free from Death MI / Death QMI
(up to 5 yrs)
100
90
80
Freedom from Death MI/Death QMI
70
60
50
0
180
360
540
720
900
1080
1280
1440
1620
1800
Time After Initial Procedure (days)
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SIRIUS Survival Free from TLR / TVR (up to 5
yrs)
100
90
80
Freedom from TLR/TVR
70
60
50
0
180
360
540
720
900
1080
1280
1440
1620
1800
Time After Initial Procedure (days)
13
SIRIUS Survival Free From MACE / TVF (up to 5
yrs)
100
90
80
Freedom from MACE/TVF
70
60
50
0
180
360
540
720
900
1080
1280
1440
1620
1800
Time After Initial Procedure (days)
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SIRIUS Cumulative Incidence of Protocol ST
at risk
533
521
510.5
495
487.5
447.5
SES
Events
0
2
3
4
5
5

0.00
0.40
0.60
0.80
1.00
1.00
at risk
525
516
509
496.5
487
442.5
BMS
Events
0
4
4
4
4
4

0.00
0.80
0.80
0.80
0.80
0.80
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SIRIUS Cumulative Incidence of ARC
Definite/Probable ST
10.0
8.0
6.0
Cumulative Incidence of ARC ST
4.0
2.0
0.0
0
180
360
540
720
900
1080
1280
1440
1620
1800
Time After Initial Procedure (days)
at risk
533
521
515
502.5
487.5
447.5
SES
Events
0
2
3
4
5
6

0.00
0.40
0.60
0.80
1.00
1.20
at risk
525
515
510.5
501
485
440.5
BMS
Events
0
6
7
8
8
9

0.00
1.10
1.30
1.50
1.50
1.80
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SIRIUS Cumulative Incidence of Any ARC ST
10.0
Sirolimus-Eluting
Control
8.0
6.0
Cumulative Incidence of ARC ST
4.0
2.0
0.0
0
180
360
540
720
900
1080
1280
1440
1620
1800
Time After Initial Procedure (days)
at risk
533
521.5
516.5
504.5
489.5
448.5
SES
Events
0
3
7
12
17
20

0.00
0.60
1.30
2.30
3.30
3.90
at risk
525
515
510.5
503
486
443
BMS
Events
0
7
8
13
15
21

0.00
1.30
1.50
2.50
2.90
4.20
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SIRIUS Changes in Clinical Events
(Control-Sirolimus) _at_ 9 mos and 5 yrs
?
?
?
?
?
?
?
?
For all clinical endpoints, there is an increase
in the difference between control and sirolimus
event rates from 9 mos to 5 yrs!
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SIRIUS Clinical Events 1-5 yrs
Major Adverse Cardiac Events
No significant differences in any of the clinical
event endpoints between 1-5 yrs
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SIRIUS - TLR Events _at_ 5 Years
events prevented per
Sirolimus
Control
P-value
1,000 pts
Overall
9.4
24.3
149
lt0.001
M
ale
10.1
24.9
149
lt0.001
Female
7.5
22.8
153
lt0.001
Diabetes
13.7
33.1
194
lt0.001
No Diabetes
8.0
20.8
129
lt0.001
LAD
11.5
28.4
168
lt0.001
Non-LAD
7.7
21.4
137
lt0.001
Small Vessel (lt2.75)
13.3
26.0
127
lt0.001
Large Vessel
5.6
22.6
170
lt0.001
Short Lesion
9.3
21.8
125
lt0.001
Long Lesion (gt13.5)
9.7
26.8
170
lt0.001
Overlap
11.0
30.1
191
lt0.001
No Overlap
8.6
21.6
130
lt0.001
Odds Ratio 95 CI
0.0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1.0
1.1
1.2
1.3
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1.0
1.1
1.2
1.3
Sirolimus better
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SIRIUS 5-Year Follow-upConclusions (1)
In this analysis of the 5-year clinical F/U from
SIRIUS (93.8 FU compliance), comparing
sirolimus-eluting stents with bare metal control
stents

• The highly significant differences (Plt0.0001)
  between sirolimus and control stents for all
  clinical event endpoints were sustained at 5-year
  F/U.
• Safety parameters (death and MI) were
  infrequently observed and remained similar in
  both groups. These late clinical events reflect
  the expected natural history of patients with
  coronary artery disease.

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SIRIUS 5-Year Follow-upConclusions (2)

• Cumulative stent thrombosis (according to both
  original protocol and ARC definitions) show no
  significant differences between the sirolimus and
  control stents
• Between 9 mos and 5 yrs clinical F/U, the marked
  differences between sirolimus and control stents
  for all clinical endpoints and for all subgroups
  has remained constant.

Thus, the previously reported safety and
efficacy findings of sirolimus-eluting stents in
the SIRIUS trial are durable at the 5-year
follow-up timepoint!
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Back-up Slides
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SIRIUS Changes in Clinical Events
(Control-Sirolimus) _at_ 1 and 5 yrs
?
?
?
?
?
?
?
?
For all clinical endpoints, there is an increase
in the difference between control and sirolimus
event rates from 1 to 5 yrs!
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SIRIUS Stent Thrombosis _at_ 5 Yrs
 
 
fwilkes1 Option 2 for ST
Overall (0-1800d)
Early(0-30d)
Late(31-360d)
Very Late (n361-1800d)
P-value (overall)
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SIRIUS Stent Thrombosis _at_ 5 Yrs
fwilkes1 Option 3 for ST
P NS for all comparisons
Sirolimus (n 533)
Control (n 525)