Transcript Potential conflicts of interest Speaker’s name: George Dangas  I have the following potential conflicts of interest to report:  Research contracts x Consulting.

Potential conflicts of interest
Speaker’s name: George Dangas
 I have the following potential conflicts of interest to report:
 Research contracts
x Consulting (speaker honoraria – modest level)
Abbott (spouse), Cordis, Astra-Zeneca and The Medicines Co.
 Employment in industry
 Stockholder of a healthcare company
 Owner of a healthcare company
 Other(s)
 I do not have any potential conflict of interest
Impact of the Everolimus-Eluting Drug Eluting Stent
on Stent Thrombosis: A Meta-Analysis of 13
Randomized Trials involving 17,074 Patients
Usman Babera MD MS, Roxana Mehrana MD, Samin K. Sharmaa MD, Somjot Brarb MD MPH, Jennifer Yua MD, Jung-Won Suhd,
Hyo-Soo Kimd MD, Seung-Jung Parke MD PhD, Antoinette de Waha MDf, Prakash Krishnana MD, Pedro Morenoa MD,
Joseph Sweenya MD, Michael C. Kima MD, Javed Sulemana MD, Robert Pyoa MD, Jose Wileya MD, Jason Kovacica MD PhD,
Annapoorna S. Kinia MD, George D. Dangasa MD PhD
aMount
Sinai Medical Center, New York, NY bKaiser Permanente, Pasadena, CA cCardiovascular Research Foundation, New York,
NY dSeoul National University Hospital, Seoul, Korea eAsan Medical Center, Seoul, Korea fDeutsches Herzzentrum,
Technische Universität, Munich, Germany
Baber et al, JACC 2011
Background
• Stent thrombosis (ST) remains a safety concern following
drug eluting stent (DES) use, particularly with first
generation DES
• Second generation DES, including the everolimus-eluting
stent (EES), were designed to improve DES safety while
maintaining efficacy
• Whether or not the novel design features of the EES
results in lower ST has not been fully explored
Baber et al, JACC 2011
Methods
• We conducted a meta-analysis of randomized
controlled trials comparing the EES to other
(comparator) DES.
• MEDLINE, Cochrane library databases searched
using keywords “everolimus”, “Xience V”,
“Promus” and “stent thrombosis”.
• Major conference proceedings also searched and
PI’s of trials contacted to provide additional data.
Baber et al, JACC 2011
Methods
• Primary endpoint was Academic Research Consortium
definite or probable ST. Secondary endpoints included
cardiac mortality, target vessel revascularization and
myocardial infarction.
• Pooled treatment effect obtained using random effects
model. Heterogeneity of treatment effect and
publication bias also evaluated.
• Additional analyses performed to assess consistency of
effect and associations with baseline risk.
Baber et al, JACC 2011
Trials Included
Year
Published
Comparator
DES
Sample Size
(EES/non-EES)
Follow-up,
months
Clopidogrel
duration,
months
Age, years
Male, %
Diabetes, %
Complex
lesion, %
Acute
Presentation, %
Spirit II
2009
PES
223/77
48
6
62
73
23
79
28
Spirit III
2009
PES
669/332
36
6
63
73
29
NA
21
Basket Prove
2010
SES
774/775
24
12
66
75
16
14
65
Compare
2010
PES
897/903
24
12
63
71
18
74
60
Isar Test 4
2009
SES
652/652
12
6
67
76
29
73
41
Resolute All
Comers
2010
ZES
1125/1140
24
6
64
77
23
21
53
Sort Out IV
2010
SES
1390/1384
9
12
64
75
14
57
42
Spirit IV
2010
PES
2458/1229
24
12
63
68
32
11
28
Excellent
2010
SES
1067/361
9
6
63
64
38
NA
50
Essence DM
2010
SES
149/151
12
NA
63
59
100
NA
42
Long DES III
2011
SES
224/226
12
12
63
70
30
41
43
Burzotta et al
2011
SES
75/75
18
12
65
80
29
100
44
Park et al
2011
SES
34/32
9
12
61
50
29
100
41
-
-
9737/7337
20.8
-
-
72
26
39
44
Cumulative
Baber et al, JACC 2011
Meta-Analysis Characteristics
• 13 trials reported from 2009 to 2011
• n= 17,097 patients (9737 EES vs 7337 control)
– Male 72%, DM 26%, ACS 44%, Complex lesions 39%
• F/U duration 9-48 months (mean 20.8)
• Clopidogrel duration 6-12 months
• Adequate statistical power to detect a 35%
RRR in comparison to a control event rate of
1.5%
Baber et al, JACC 2011
Stent Thrombosis
Baber et al, JACC 2011
Target Vessel Revascularization
Baber et al, JACC 2011
Myocardial Infarction
Baber et al, JACC 2011
Cardiac Death
Baber et al, JACC 2011
Stent Thrombosis
TVR
MI
Statistical Model
Random (13)
Fixed (13)
Clopidogrel Duration
6 months (5)
12 months (7)
Follow-up
≤ 1 year (12)
> 1 year (7)
DES
PES (5)
ZES (1)
SES (7)
0.1
1
Favors EES
10
Favors non-EES
0.4 Favors EES
Favors non-EES
4
0.4
Favors EES
Favors non-EES
4
ST Regression Analysis
R2=0.89, p<0.001
Risk Difference, %
0.5
Sirolimus eluting stent
Zotarolimus eluting stent
Paclitaxel eluting stent
-0.5
-1.5
-2.5
-3.5
0
1
2
3
Non everolimus-eluting drug eluting stent ST rate, %
Baber et al, JACC 2011
4
Limitations
• Lack of patient-level data
• Second generation DES comparator in one study
alone
• Unable to explore timing of ST with respect to
dual antiplatelet therapy (DAPT) cessation
Conclusions
• The EES is associated with large reduction in ARC definite
or probable ST. Concordant reductions in TVR and MI.
• Benefits increase in dose-dependent fashion with greater
baseline risk.
 In accordance to the baseline ST risk within each
subgroup, risk reduction greatest against PES,
intermediate against ZES and smallest against SES.
Baber et al, JACC 2011