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CYPHER ® Stent vs. Taxus Stent: Randomized Trials Kastrati A., et al., ACC 2007 Oral Presentat
CYPHER® Stent vs. Taxus Stent:Randomized Trials
Kastrati A., et al., ACC 2007 Oral Presentation.
The ACC/AHA and ESC GuidelinesThe ACC/AHA and ESC Guidelines
American College of Cardiology/American Heart Association (ACC/AHA) Style
Classification of Evidence1:• Level of Evidence A:
Data derived from multiple randomized clinical trials• Level of Evidence B:
Data derived from a single randomized trial or nonrandomized studies• Level of Evidence C:
Consensus opinion of experts.
1 Smith, et al., JACC 2001; 37: 2215-38.2 Silber S., et al., EHJ 2005; 26:804-47.
European Society of Cardiology (ESC) Classification of Evidence2:• Level of Evidence A:
Data derived from multiple randomized clinical trials or meta-analyses• Level of Evidence B:
Data derived from a single randomized trial or large non-randomized studies• Level of Evidence C:
Consensus opinion of experts and / or small studies, retrospective studies, registries
Keeley et al, Lancet 2003
Meta-analysis of RCTs
70
80
90
100
1 2 3 40
Thrombolysis
PTCA
time after discharge (years)
surv
iva
l (%
)
Every et al, NEJM 1996
Registry Study
Randomized vs. Observational Studies: Lessons from AMI Studies
Kastrati A., et al., ACC 2007 Oral Presentation.
Cheung et al, Br J Clin Pharmacol 2004
SimvaPravaPravaLovaPravaSimvaFluvaPravaAtorva
Uniformity of results across RCTs is rarely achieved
Kastrati A., et al., ACC 2007 Oral Presentation.
Uniformity of RCT Results: Lessons from Statin Studies
To assess and compare long-term outcomes in randomized trials of
sirolimus-eluting stents (SES)
vs.paclitaxel-eluting stents (PES)
Objective of the Meta-Analysis
Kastrati A., et al., ACC 2007 Oral Presentation.
• Randomized trial, published or presented at
meetings assessing sirolimus-eluting stent
(SES) vs. paclitaxel-eluting stent (PES)
Inclusion Criteria
Kastrati A., et al., ACC 2007 Oral Presentation.
Outcomes of interest:- Stent thrombosis- All-cause mortality- Composite of death or myocardial infarction (MI)- Composite of death, MI or reintervention (MACE)
during the entire available follow-up interval
Study Endpoints
Kastrati A., et al., ACC 2007 Oral Presentation.
• Mantel-Cox method for calculating hazard ratios for individual trials
• Fixed and random effect models for calculating overall harzard ratios and check for heterogeneity
• Kaplan-Meier survival curves for all trials combined
Statistical Methods
Kastrati A., et al., ACC 2007 Oral Presentation.
Overall
TAXI
SORT-OUT II
REALITY
ISAR-SMART 3
ISAR-DIABETES
ISAR-DESIRE
CORPAL
BASKET
Trial
LONGDES II
7,480
202
2,098
1,353
360
250
200
652
545
Total No.of patients
500
Mean Clinical FU in months
36.9
9.0
24.1
33.9
32.1
33.9
30.5
18.2
13.0
20.0
PROSIT 308 12.0
SIRTAX 1,012 24.2
Included SES vs. PES Trials
Kastrati A., et al., ACC 2007 Oral Presentation.
Overall
Trial
5,074
Total No.of patients
Mean Clinical FU in months
TAXI 202 36.9
REALITY 1,353 24.1
ISAR-SMART 3 360 33.9
ISAR-DIABETES 250 32.1
ISAR-DESIRE 200 33.9
CORPAL 652 30.5
BASKET 545 18.2
LONGDES II 500 13.0
25.1
SIRTAX 1,012 24.2
Trials That Provide Individual Patient Data
Kastrati A., et al., ACC 2007 Oral Presentation.
Patients at Risk
SESPES
25392535
24832457
23192311
21512121
16531603
573533
Pro
bab
ilit
y o
f S
ten
t T
hro
mb
osi
s, %
0
1
2
3
4
5
0 6 12 18 24 30
Paclitaxel-eluting stentSirolimus-eluting stent
Months After Randomization
Cumulative Incidence of Stent Thrombosis
Kastrati A., et al., ACC 2007 Oral Presentation.
TAXI
SIRTAX REALITY
LONG-DES II ISAR-SMART 3 ISAR-DIABETES ISAR-DESIRE CORPAL BASKET
Overall
.1 101
4/264 5/281 2/331 4/321
0/100 2/100
0/125 2/125 1/180 1/180 1/250 5/250
6/684 18/669 12/503 15/509
2/102 2/100
28/2693 56/2689
Trial
No. of events / Total No. of patients
SES group PES group
FavorsSES
FavorsPES
Hazard Ratio
0.54 (0.34, 0.85)
Test for Heterogeneity: Cochran Q=5.3 (d.f.=9) P=.81
Test for Inconsistency: I2 =0.0%
PROSIT 0/154 2/154
SORT-OUT II NA
Risk of Stent Thrombosis
Kastrati A., et al., ACC 2007 Oral Presentation.
0.24 0.54 0.34 0.85 1.08
BASKET
CORPAL
ISAR-DESIRE
ISAR-DIABETES
ISAR-SMART 3
LONG-DES II
PROSIT
REALITY
SIRTAX
TAXI
Study ommited Meta-analysis random-effects estimates (exponential form)
Influence of Individual Trials
Kastrati A., et al., ACC 2007 Oral Presentation.
Patients at Risk
SESPES
25392535
24982475
23362338
21702152
16661631
608552
50
60
70
80
90
100
0 6 12 18 24 30
Paclitaxel-eluting stentSirolimus-eluting stent
Months After Randomization
Pro
babi
lity
of S
urvi
val,
%
Kastrati A., et al., ACC 2007 Oral Presentation.
Kaplan-Meier (K/M) Curves of Survival
TAXI
SIRTAX REALITY
LONG-DES II ISAR-SMART 3 ISAR-DIABETES ISAR-DESIRE CORPAL BASKET
Overall
.1 101
10/264 11/281 18/331 22/321
8/100 6/100
21/125 22/125 10/180 13/180
2/250 0/250
23/684 23/669 25/503 25/509
7/102 3/100
148/3758 153/3722
Trial
No. of events / Total No. of patients
SES group PES groupFavors
SESFavorsPES
Test for Heterogeneity: Cochran Q=5.3 (d.f.=10) P=.87
Test for Inconsistency: I2 =0.0%Hazard Ratio
0.93 (0.74, 1.16)
PROSIT 5/154 9/154
SORT-OUT II 19/1065 19/1033
Risk of Death
Kastrati A., et al., ACC 2007 Oral Presentation.
Patients at Risk
SESPES
25392535
24012361
22362230
20802043
15961545
581529
50
60
70
80
90
100
0 6 12 18 24 30
Paclitaxel-eluting stentSirolimus-eluting stent
Months After Randomization
Pro
babi
lity
of S
urvi
val F
ree
of M
I, %
Kastrati A., et al., ACC 2007 Oral Presentation.
K/M Curves of Survival Free of MI
TAXI SIRTAX REALITY LONG-DES II ISAR-SMART 3 ISAR-DIABETES ISAR-DESIRE CORPAL BASKET
Overall
.1 101
23/264 29/281 33/331 37/321
11/100 10/100
26/125 26/125 19/180 19/180 22/250 27/250 54/684 69/669 41/503 46/509 11/102 10/100
240/2539 273/2535
Trial
No. of events / Total No. of patients
SES group PES groupFavors
SESFavorsPES
Test for Heterogeneity: Cochran Q=1.2 (d.f.=8) P=.99
Test for Inconsistency: I2 =0.0%Hazard Ratio
0.86 (0.72, 1.02)
Risk of Death or MI
Kastrati A., et al., ACC 2007 Oral Presentation.
Patients at Risk
SESPES
25392535
23742313
21142061
19411855
14681371
527467
50
60
70
80
90
100
0 6 12 18 24 30
Paclitaxel-eluting stentSirolimus-eluting stent
Months After Randomization
Pro
babi
lity
of S
urvi
val F
ree
of M
AC
E,
%
Kastrati A., et al., ACC 2007 Oral Presentation.
K/M Curves of Survival Free of MACE
TAXI
SIRTAX REALITY
LONG-DES II ISAR-SMART 3 ISAR-DIABETES ISAR-DESIRE CORPAL BASKET
Overall
.1 101
32/264 35/281 51/331 52/321
23/100 37/100
30/125 30/125 34/180 47/180 27/250 42/250
93/684 104/66957/503 87/509
14/102 9/100
453/3758 550/3722
Trial
No. of events / Total No. of patients
SES group PES groupFavors
SESFavorsPES
Test for Heterogeneity: Cochran Q=12.2 (d.f.=10) P=.27
Test for Inconsistency: I2 =18.2%
Hazard Ratio
0.79 (0.69, 0.91)
PROSIT 9/154 18/154
SORT-OUT II 83/1065 89/1033
Kastrati A., et al., ACC 2007 Oral Presentation.
Risk of MACE
0.65 0.79 0.69 0.91 0.95
BASKET
CORPAL
ISAR-DESIRE
ISAR-DIABETES
ISAR-SMART 3
LONG-DES II
PROSIT
REALITY
SIRTAX
SORT-OUT II
TAXI
Study ommited Meta-analysis random-effects estimates (exponential form)
Kastrati A., et al., ACC 2007 Oral Presentation.
Influence of Individual Trials
• With ~7500 patients randomized between CYPHER® and Taxus drug-eluting stents, we are provided with the most abundant evidence of randomized stent vs. stent trials ever accumulated.
• There is no significant heterogeneity across trials with respect to the treatment effect.
Kastrati A., et al., ACC 2007 Oral Presentation.
Conclusions I
• Compared with Taxus stent, CYPHER® stent is associated with:
– No significant difference in mortality
– A significantly lower risk of stent thrombosis
– A trend toward a lower combined risk of death or myocardial infarction
– A significantly lower risk of death, myocardial infarction or reintervention
Kastrati A., et al., ACC 2007 Oral Presentation.
Conclusions II
