1. Columbia / CRF DES vs. BMS Meta-Analysis Kirtane et al, Circ 2009;119: 3198-3206

2. DES Studies: Data Synthesis In order to synthesize the existing data, we performed a systematic review and meta-analysis of all DES vs. BMS studies through 2/08 In order to synthesize the existing data, we performed a systematic review and meta-analysis of all DES vs. BMS studies through 2/08  To derive summary estimates of all- cause mortality, MI, and TVR in studies with ≥1 year of follow-up  To specifically assess differences between on-label / off-label use, and between RCT and observational data Kirtane et al, Circ 2009;119: 3198-3206

3. Methods: Inclusion Criteria English language RCTs or registries which reported a direct comparison of DES (commercialized formulations of SES and PES only) vs. BMS up through February 2008 English language RCTs or registries which reported a direct comparison of DES (commercialized formulations of SES and PES only) vs. BMS up through February 2008 Criteria for each study: Criteria for each study:  ≥100 patients total  Mortality reported (± MI and/or TVR)  ≥1 year of cumulative follow-up reported, with the outcome assessed at the same time point in both comparator arms Kirtane et al, Circ 2009;119: 3198-3206

4. Study Flow Diagram Pubmed search thru 2/08: stent AND bare AND (eluting OR sirolimus OR paclitaxel) 834 articles 221 review articles or editorials 115 no/unclear clinical outcomes described 104 sub-studies/more recent papers 81 no BMS/DES comparison 100 basic science or non-approved device 84 with <1 year f/u or <100 pts 92 case reports, meta-analyses, non- coronary studies, or other 56 studies EuroIntervention search (146 articles) 3 articles met criteria AHA (3/246), TCT (9/206), ESC (4/243), ACC (0/468) abstracts and reference searches 16 abstracts met criteria RCT studies: 22 (9,470 patients) Registry studies: 34 (182,901 patients) 37 articles Kirtane et al, Circ 2009;119: 3198-3206

5. All-Cause Mortality: All RCTs 8,867 patients, 21 trials, mean F/U 2.9 years Favors BMS Estimate (95% CI) Weight (%) 0.97 (0.81,1.15) 0.97 (0.81,1.15), p=0.72 Random Effects *Fixed Effects (I 2 =0.0%) Favors DES Kirtane et al, Circ 2009;119: 3198-3206

6. All-Cause Mortality: RCT’s (Off-Label) 4,049 patients, 12 trials, mean F/U 1.5 years Favors DESFavors BMS Estimate (95% CI) Weight (%) 0.84 (0.62,1.13) 0.84 (0.62,1.13), p=0.24 Random Effects *Fixed Effects (I 2 =0.0%) Kirtane et al, Circ 2009;119: 3198-3206

7. MI: All RCTs 8,850 patients, 20 trials, mean F/U 2.9 years Estimate (95% CI)Weight (%) 0.94 (0.78,1.13) 0.95 (0.79,1.13), p=0.54 Favors DESFavors BMS Random Effects *Fixed Effects (I 2 =3.0%) Kirtane et al, Circ 2009;119: 3198-3206

8. MI: RCT’s (Off Label) 4,532 patients, 12 trials, mean F/U 1.5 years Estimate (95% CI) Weight (%) Favors DESFavors BMS 0.77 (0.54,1.10) 0.83 (0.62,1.10), p=0.19 Random Effects *Fixed Effects (I 2 =25.5%) Kirtane et al, Circ 2009;119: 3198-3206

9. TVR: All RCTs 7,291 patients, 16 trials, mean F/U 3.2 years Favors DESFavors BMS Estimate (95% CI)Weight (%) 0.45 (0.37,0.54), p<0.001 0.51 (0.45,0.57) *Random Effects (I 2 =53.2%) Fixed Effects Kirtane et al, Circ 2009;119: 3198-3206

10. TVR: RCTs (Off Label) 2,673 patients, 8 trials, mean F/U 1.6 years Favors DESFavors BMS Estimate (95% CI)Weight (%) 0.38 (0.27,0.52), p<0.001 0.42 (0.34,0.52) *Random Effects (I 2 =47.8%) Fixed Effects Kirtane et al, Circ 2009;119: 3198-3206

11. TVR: RCTs Meta-Regression on Percent Angiographic F/U *log(HR) regressed on percentage of pts with angiographic f/u; figure displayed on exponentiated scale p=0.73 *Hazard Ratio Percentage of Patients with Angiographic F/U

12. All-Cause Mortality: All Registries 169,595 patients, 31 registries, mean F/U 2.5 years Favors BMS Estimate (95% CI) Weight (%) 0.78 (0.71,0.86), p<0.001 0.81 (0.78,0.85) Favors DES *Random Effects (I 2 =71%) Fixed Effects Kirtane et al, Circ 2009;119: 3198-3206

13. All-Cause Mortality: Adjusted Registries 136,558 patients, 19 registries, mean F/U 2.7 years Favors BMS Estimate (95% CI)Weight (%) 0.79 (0.71,0.89), p<0.001 0.82 (0.79,0.86) Favors DES *Random Effects (I 2 =76%) Fixed Effects Kirtane et al, Circ 2009;119: 3198-3206

14. MI: All Registries 130,191 patients, 25 registries, mean F/U 2.5 years Favors DESFavors BMS Estimate (95% CI)Weight (%) 0.87 (0.78,0.97), p=0.01 0.95 (0.91,1.00) *Random Effects (I 2 =60%) Fixed Effects *MI is QWMI in Washington Hospital Center, RESTEM Kirtane et al, Circ 2009;119: 3198-3206

15. TVR: All Registries 74,154 pts, 18 registries, mean F/U 2.2 years Favors DESFavors BMS Estimate (95% CI)Weight (%) 0.54 (0.48,0.61), p<0.001 0.57 (0.54,0.60) *Random Effects (I 2 =70%) Fixed Effects Kirtane et al, Circ 2009;119: 3198-3206

16. Summary: DES vs. BMS Treatment Effect Estimates MortalityMITVRRCTs 8,867 pts, 21 trials 8,850 pts, 20 trials 7,291 pts, 16 trials - Fixed effects - Random effects 0.970.970.950.940.510.45 Registries 169,595 pts, 31 studies 130,191 pts, 25 studies 74,154 pts, 18 studies - Fixed effects - Random effects 0.810.780.950.870.570.54 <1.0  DES better Kirtane et al, Circ 2009;119: 3198-3206

17. First Author Journal DES pts BMS pts F/U Years DES Mortality BMS Mortality pGroeneveldJACC71,96571,965210.7%13.5%<0.001 ShisheborJACC6,0531,9834.58.0%17.0%<0.001 WangCCI3,4174,14916.0%11.4%<0.0001 Anstrom Arch Int Med 1,5013,16528.6%8.6%0.94 Austin Circ Interventions 1,1056,39426.6%7.7%0.04 VlaarCCI53655726.4%6.4%0.93 YanIJC23943310.5%2.9%0.07 Alidoosti Hellen J Card 22815681.55.3%4.7%0.10 Dominguez Franco Clin Cardiology 2052151.56.3%8.4%NS RamanaCCI14117036.0%12.0%0.05 NuscaAJC121113312.0%21.0%<0.05 GarroEurointervention11712824.4%4.1%1.0 Okada Circ J 80124116.3%19.8%0.49 AssaliEurointervention684322.9%4.7%0.60 Malenka et al (JAMA) excluded for DES era/BMS era comparison; 4 additional studies reported cardiac death only 14 Subsequent DES vs. BMS Registries 14 Subsequent DES vs. BMS Registries Published 2/08-9/08 (N=176,777 pts)* *Studies already included in meta-analysis in unpublished format not listed