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