1. Unrestricted Use of Drug-Eluting Stents Compared with Bare-Metal Stents in Routine Clinical Practice: Findings From the National Heart, Lung, and Blood Institute Dynamic Registry J. Dawn Abbott, MD, FACC,* Matthew R. Voss, MD,* Mamoo Nakamura, MD,† Howard A. Cohen, MD, FACC,‡ Faith Selzer, PHD,† Kevin E. Kip, PHD, Helen A. Vlachos, MSC,†Robert L. Wilensky, MD, FACC,§ David O. Williams, MD, FACC* Providence, Rhode Island; Pittsburgh and Philadelphia, Pennsylvania; and New York, New York Abbott, J. D. et al. J Am Coll Cardiol 2007;50:2029-36

2. Drug-eluting vs. Bare Metal Stents: Background n Stents are utilized almost uniformly in patients undergoing percutaneous coronary intervention n Until recently, drug-eluting stents have been the preferred treatment n Some have raised concerns that drug-eluting stents may be associated with more frequent stent thrombosis leading to excess death and MI n Robust comparisons of drug-eluting and bare metal stents have been limited to highly selected, simple patient subgroups. n Comparisons between DES and BMS for non-protocol usage in North America have been limited

3. Drug-eluting vs. Bare Metal Stents: Purpose of Investigation In the setting of routine clinical practice to: n Determine and compare the baseline clinical and angiographic features, procedural strategies and clinical outcomes of patients treated with a bare metal and drug-eluting stent n Compare outcomes following adjustments for baseline imbalances

4. Dynamic Registry  Prospective observational multicenter study  Enrollment of sequential “waves” of consecutive patients having coronary intervention  Exclusion: Refusal or inability to provide written informed consent  2000 patients per wave separated by 18 months  Trained research coordinators collect data  Oversampling of women and minorities  Follow-up obtained by phone at 30 days, 6 months, 1 year  Funding just received to follow patients for five years

5. Study Design n Identified patients treated with DES in Wave 4 (2004) and compared them to patients treated with a BMS in Wave 3 (2002) n Wave 3 represented the last wave before the routine availability of DES n Intent of excluding wave 4 BMS patients was to eliminate selection bias seen in Wave 4 n Patients treated with BMS in Wave 3 would likely have been treated with DES had one been available n One-year follow-up data was available in 93% of wave 3 patients and 96% of wave 4 patients

6. DES vs. BMS: Study Population BMS Era October 2001 to March 2002 N=2047 DES Era February to May 2004 N=2112 Exclude if no stent N=284 Exclude if only BMS or no stent N=652 BMS Group N=1763 2551 lesions DES Group N=1460 1995 lesions SES 59.8% PES 31.5%

7. Statistical Analysis n Univariate differences between BMS and DES u Categorical variables: chi-square test u Continuous data: Wilcoxon rank-sum test n Cumulative one-year event rates u Kaplan-Meier approach and compared by log-rank statistic n Multivariable analysis u Cox proportional hazards regression used to estimate unadjusted and adjusted hazard ratios of adverse clinical outcomes n Probability values <0.05 were considered significant

8. VariableBMS n=1763 DES n=1460 p-value Mean Age (years) 64.463.70.07 % Female 35.833.30.14 Diabetes, % 29.134.30.001 Hypertension, % 74.179.10.001 Hypercholesterolemia, % 69.877.5<0.0001 Current smoking, % 24.421.40.05 Prior myocardial infarction, % 26.226.40.90 Prior coronary bypass, % 17.419.10.21 Prior angioplasty, % 27.332.40.002 Renal insufficiency 7.19.10.03 DES vs. BMS: Baseline Characteristics

9. VariableBMS n=1763 DES n=1460 p-value Vessel Disease0.098 Single37.633.8 Double32.032.5 Triple30.133.5 Indication for procedure, % <0.0001 Acute MI29.823.8 Unstable Angina39.935.9 Stable Angina19.725 Other10.615.3 Ejection Fraction, mean51.552.30.09 Cardiogenic Shock2.10.5<0.0001 DES vs. BMS: Baseline Characteristics

10. VariableBMS n=2551 DES n=1995 p-value Mean Reference Vessel Diameter 3.13.00.07 Mean Lesion Length 13.415.9<0.0001 Lesion Types, % Total Occlusion 9.27.40.03 Thrombus 15.411.0<0.0001 Calcified 22.326.50.001 Bifurcation 13.210.20.002 Ostial 6.98.80.02 Lesion Tortuosity, % None/Mild 75.073.20.19 Moderate/Severe Tortuosity 2526.8 DES vs. BMS:Attempted Lesion Characteristics

11. DES vs. BMS: DES vs. BMS: Procedural Characteristics BMS n= 2551 DES n=1995 p-value Lesion Complication, % Abrupt Closure0.20.00.03 Dissection1.92.10.80 Side Branch Occlusion2.12.20.85 Persistent flow reduction0.70.90.68 Procedural Success, %0.16 Complete96.597.3 Partial3.22.2 Failure0.30.5 Angiographic success, %97.598.00.33

12. VariableBMS n=176 3 DES n=1460 p- value Death 1.10.50.06 MI 1.92.20.60 CABG 0.30.10.10 MACE (Death, Any MI, Any CABG) 3.22.60.29 Bleeding Requiring Transfusion 1.61.30.50 DES vs. BMS: DES vs. BMS: In-hospital Unadjusted Event Rates

13. VariableBMS n=1763 DES n=1460 p-value Death 4.33.60.32 MI 4.74.60.93 CABG 3.11.2<0.001 Target Vessel Revascularization 9.25.0<0.001 Repeat PCI 12.79.00.001 MACE (Death, MI, Repeat Revascularization) 20.915.5<0.001 DES vs. BMS: DES vs. BMS: Cumulative Unadjusted One-Year Event Rates

14. Stent Thrombosis n Definite stent thrombosis reported n Over 1 year 1.0% of DES patients (n=14) u 0.8% (n=11) subacute u 0.2% (n=3) late n Data were not collected during wave 3 u not available for BMS patients

15. DES vs. BMS: Adjusted and Unadjusted Events at One-Year

16. Copyright ©2007 American College of Cardiology Foundation. Restrictions may apply. Abbott, J. D. et al. J Am Coll Cardiol 2007;50:2029-2036 Adjusted Kaplan-Meier Event Curves at 1 Year Freedom from (A) Death/MI (B) Repeat Revascularization

17. One-year Event Rates for complex lesion types According to Stent Type

18. Copyright ©2007 American College of Cardiology Foundation. Restrictions may apply. Abbott, J. D. et al. J Am Coll Cardiol 2007;50:2029-2036 Adjusted HRs and 95% CIs for 1 Year (A) Death/MI (B) TVR

19. DES vs. BMS: Conclusions n DES as used in routine clinical practice in patients with complex lesions resulted in a substantial reduction in clinically driven target vessel revascularization compared with BMS-treated patients n Overall risk of repeat revascularization after adjustment was 43% lower in DES patients n No excess hazard of death/MI and a low rate of stent thrombosis observed in DES patients at one-year n These findings support the use of DES in routine clinical practice n Extended follow-up is needed to determine incidence of very late stent thrombosis