1. 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

2. 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

3. 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

4. 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

5. 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

6. 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 II2009PES223/774866273237928 Spirit III2009PES669/332366637329NA21 Basket Prove2010SES774/77524126675161465 Compare2010PES897/90324126371187460 Isar Test 42009SES652/6521266776297341 Resolute All Comers 2010ZES1125/11402466477232153 Sort Out IV2010SES1390/13849 12 6475145742 Spirit IV2010PES2458/122924126368321128 Excellent2010SES1067/36196636438NA50 Essence DM2010SES149/15112NA6359100NA42 Long DES III2011SES224/22612 6370304143 Burzotta et al2011SES75/75181265802910044 Park et al2011SES34/3291261502910041 Cumulative- - 9737/733720.8--72263944 Baber et al, JACC 2011

7. 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

8. Stent Thrombosis Baber et al, JACC 2011

9. Target Vessel Revascularization Baber et al, JACC 2011

10. Myocardial Infarction Baber et al, JACC 2011

11. Cardiac Death Baber et al, JACC 2011

12. 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

13. 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

14. 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

15. 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