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 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 Baber a MD MS, Roxana Mehran a MD, Samin K. Sharma a MD, Somjot Brar b MD MPH, Jennifer Yu a MD, Jung-Won Suh d, Hyo-Soo Kim d MD, Seung-Jung Park e MD PhD, Antoinette de Waha MD f, Prakash Krishnan a MD, Pedro Moreno a MD, Joseph Sweeny a MD, Michael C. Kim a MD, Javed Suleman a MD, Robert Pyo a MD, Jose Wiley a MD, Jason Kovacic a MD PhD, Annapoorna S. Kini a MD, George D. Dangas a MD PhD a Mount Sinai Medical Center, New York, NY b Kaiser Permanente, Pasadena, CA c Cardiovascular Research Foundation, New York, NY d Seoul National University Hospital, Seoul, Korea e Asan Medical Center, Seoul, Korea f Deutsches 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, yearsMale, %Diabetes, % Complex lesion, % Acute Presentation, % Spirit II2009PES223/ Spirit III2009PES669/ NA21 Basket Prove2010SES774/ Compare2010PES897/ Isar Test 42009SES652/ Resolute All Comers 2010ZES1125/ Sort Out IV2010SES1390/ Spirit IV2010PES2458/ Excellent2010SES1067/ NA50 Essence DM2010SES149/15112NA NA42 Long DES III2011SES224/ Burzotta et al2011SES75/ Park et al2011SES34/ 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

Statistical Model Random (13) Random (13) Fixed (13) Fixed (13) Clopidogrel Duration 6 months (5) 6 months (5) 12 months (7) 12 months (7)Follow-up ≤ 1 year (12) ≤ 1 year (12) > 1 year (7) > 1 year (7)DES PES (5) PES (5) ZES (1) ZES (1) SES (7) SES (7) Stent Thrombosis TVR MI Stent Thrombosis TVR MI Favors EES Favors non-EES

ST Regression Analysis Non everolimus-eluting drug eluting stent ST rate, % Risk Difference, % R 2 =0.89, p<0.001 Sirolimus eluting stent Zotarolimus eluting stent Paclitaxel 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