speaker’s name: george dangas i have the following potential conflicts of interest to report: ...
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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 Abbott (spouse), Cordis, Astra-Zeneca and The Medicines Co.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
Potential conflicts 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 IncludedYear
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
Cumulative - - 9737/7337 20.8 - - 72 26 39 44
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
Statistical ModelStatistical Model
Random (13)Random (13)
Fixed (13)Fixed (13)
Clopidogrel DurationClopidogrel Duration
6 months (5)6 months (5)
12 months (7)12 months (7)
Follow-upFollow-up
≤ ≤ 1 year (12)1 year (12)
> 1 year (7)> 1 year (7)
DESDES
PES (5)PES (5)
ZES (1)ZES (1)
SES (7)SES (7)
Stent Thrombosis TVRStent Thrombosis TVR MI MI
Favors EES Favors non-EESFavors EES Favors non-EES Favors EES Favors non-EESFavors EES Favors non-EES Favors EES Favors non-EESFavors EES Favors non-EES
ST Regression Analysis
Non everolimus-eluting drug eluting stent ST rate, %
Ris
k D
iffe
ren
ce, %
R2=0.89, p<0.001 Sirolimus eluting stentZotarolimus eluting stentPaclitaxel eluting stent
Baber et al, JACC 2011
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