DES Should be Used as the Default Stent in ACS! Gregg W. Stone MD Columbia University Medical Center Cardiovascular Research Foundation

Disclosures Gregg W. Stone MD Advisory boards for and honoraria from Abbott Vascular and Boston Scientific Consultant to Medtronic

Harmonizing Outcomes with Revascularization and Stents in AMI UFH + GPI (n=1802) Bivalirudin (n=1800) Primary Medical Rx 193 Primary CABG 62 Deferred PCI 2 Index PCI, not eligible - PTCA only 119 - Stented 220 3602 pts with STEMI R 1:1 3006 pts eligible for stent rand. 93.1% of all stented pts were randomized R 3:1 TAXUS DES N=2257 EXPRESS BMS N=749 Randomized 18 16 • • • Withdrew • • • • • • Lost to FU • • • 7 13 1 year FU N=2225 (98.6%) N=730 (97.5%) 13 month angiographic FU 942 23 97 • • • Withdrew • • • • • • Lost to FU • • • 8 34 307 3 year FU N=2103 (93.2%) N=687 (91.7%)

Primary Efficacy Endpoint: Ischemic TLR 10 Diff [95%CI] = -3.0% [-5.1, -0.9] HR [95%CI] = 0.59 [0.43, 0.83] P=0.002 TAXUS DES (n=2257) 9 EXPRESS BMS (n=749) 8 7.5% 7 6 Ischemic TLR (%) 5 4.5% 4 3 2 1 1 2 3 4 5 6 7 8 9 10 11 12 Time in Months Number at risk TAXUS DES 2257 2132 2098 2069 1868 EXPRESS BMS 749 697 675 658 603 Stone GW et al. NEJM 2009;360:1946-59

Binary Analysis Segment Restenosis at 13 Months Patient and Lesion Level Analysis* RR [95%CI] = 0.44 [0.33, 0.57] P<0.0001 RR [95%CI] = 0.44 [0.33, 0.57] P<0.0001 Major 2 endpoint * ITT: Includes all stent randomized lesions, whether or not a stent was implanted, and whether or not non study stents were placed ** Any lesion with restenosis  per pt restenosis Stone GW et al. NEJM 2009;360:1946-59

Primary Efficacy Endpoint: Ischemic TLR Routine angiographic FU No routine angiographic FU TAXUS DES (n=911) TAXUS DES (n=1346) EXPRESS BMS (n=293) EXPRESS BMS (n=456) 2 24 22 18 16 14 12 8 6 20 10 4 2 24 22 18 16 14 12 8 6 20 10 4 1-yr HR [95%CI]= 0.58 [0.32, 1.04] 18.3% P=0.06 1-yr HR [95%CI]= 0.64 [0.43, 0.95] 12.7% Ischemic TLR (%) Ischemic TLR (%) P=0.02 10.3% 8.7% 3-yr HR [95%CI]= 3-yr HR [95%CI]= 0.53 [0.38, 0.75] 0.67 [0.48, 0.93] P=0.001 P=0.01 3 6 9 12 15 18 21 24 27 30 33 36 3 6 9 12 15 18 21 24 27 30 33 36 Months Months Number at risk Number at risk PES 911 896 878 830 812 795 596 PES 1346 1208 1164 1112 1090 1051 681 BMS 293 282 274 237 234 229 157 BMS 456 394 381 361 353 338 215 Stone GW. TCT2010.

Primary Safety Endpoint: Safety MACE* 1928 634 2037 2094 684 2257 TAXUS DES 12 15 18 21 24 27 30 33 36 749 669 Months 3 6 9 Number at risk EXPRESS BMS 1971 648 1875 615 412 1289 P=0.66 3-yr HR [95%CI]= 1.05 [0.84, 1.33] 12.9% 13.6% Safety MACE (%) 2 4 8 10 14 16 TAXUS DES (n=2257) EXPRESS BMS (n=749) P=0.92 1-yr HR [95%CI]= 1.02 [0.76, 1.36] 8.1% 8.0% * Safety MACE = death, reinfarction, stroke, or stent thrombosis Stone GW. TCT2010.

Three-Year Stent Thrombosis (ARC Definite or Probable) 6 TAXUS DES (n=2238) EXPRESS BMS (n=744) 5 4.8% 4.3% 4 3.4% Stent Thrombosis (%) 3-yr HR [95%CI]= 3 3.1% 1.10 [0.74, 1.65] 2 P=0.63 1-yr HR [95%CI]= 0.92 [0.58, 1.45] 1 P=0.72 3 6 9 12 15 18 21 24 27 30 33 36 Months Number at risk TAXUS DES 2238 2108 2066 2013 1980 1932 1341 EXPRESS BMS 744 695 683 664 654 637 425 Stone GW. TCT2010.

Stent Randomization: Aspirin and Thienopyridine Use Regular* aspirin use (%) Regular* thieno. use (%) TAXUS DES (n=2257) EXPRESS BMS (n=749) 99.1% 98.3% 98.3% 99.4% 97.5% 98.7% 97.5% 95.8% 94.6% 98.5% 98.9% 98.6% 97.4% 97.1% 97.8% 96.3% 95.7% 72.8% 87.5% P<0.001 Antiplatelet agent use (%) 63.6% All P=NS P<0.001 36.7% 28.3% 30.5% P=0.004 22.5% P=0.003 *Taken >50% of days since last visit Stone GW. TCT2010.

Three-Year All-Cause Mortality P=0.31 3-yr HR [95%CI]= 0.84 [0.60, 1.17] 5.6% 6.6% All-Cause Mortality (%) 1 2 3 4 5 6 7 8 TAXUS DES (n=2257) EXPRESS BMS (n=749) P=0.97 1-yr HR [95%CI]= 0.99 [0.64, 1.55] 2072 674 2138 2170 713 2257 TAXUS DES 12 15 18 21 24 27 30 33 36 749 702 Months 9 Number at risk EXPRESS BMS 2097 683 2026 657 443 1409 3.5% Stone GW. TCT2010.

Adapted from Ziada KM et al. JACC CI Int 2011;4;39-41 Long-term (3-5 year) FU after DES vs. BMS in AMI N=6,026 pts from 8 randomized trials  Study N Type of DES Clinical FU (mos) Angio FU DEDICATION 626 SES, PES and ZES Median 42 No PASEO 270 SES and PES Mean 41 STRATEGY 175 SES 60 SESAMI 320 36 MISSION 304 Yes TYPHOON 712 48 PASSION 619 PES HORIZONS-AMI 3,006 Adapted from Ziada KM et al. JACC CI Int 2011;4;39-41

Adapted from Ziada KM et al. JACC CI Int 2011;4;39-41 Long-term (3-5 year) FU after DES vs. BMS in AMI Stent thrombosis (N=6,026 pts)  Stent thrombosis DES BMS OR [95%CI] P DEDICATION 2.9% 3.2% 0.90 [0.36, 2.24] 0.82 PASEO 1.1% 2.2% 0.49 [0.07, 3.57] 0.48 STRATEGY 6.9% 7.9% 0.86 [0.28, 2.66] 0.79 SESAMI 5.1% 1.00 [0.37, 2.73] 1.00 MISSION 3.1% 2.0% 1.69 [0.40, 7.20] TYPHOON 5.3% 5.5% 0.90 [0.42, 2.00] 0.83 PASSION 4.2% 3.4% 1.19 [0.52, 2.69] 0.68 HORIZONS-AMI 4.4% 1.15 [0.77-1.72] 0.50 META-ANALYSIS 1.06 [0.81-1.39] 0.67 1.15 (0.77-1.72) Adapted from Ziada KM et al. JACC CI Int 2011;4;39-41

Adapted from Ziada KM et al. JACC CI Int 2011;4;39-41 Long-term (3-5 year) FU after DES vs. BMS in AMI Mortality (N=6,026 pts)  DEATH DES BMS OR [95%CI] P DEDICATION 10.5% 6.4% 1.73 [0.97, 3.08] 0.06 PASEO 8.3% 12.2% 0.65 [0.29, 1.49] 0.31 STRATEGY 18.4% 15.9% 1.19 [0.54, 2.62] 0.66 SESAMI 3.2% 5.0% 0.61 [0.20, 1.92] 0.40 MISSION 4.4% 6.6% 0.69 [0.25, 1.85] 0.46 TYPHOON 4.0% 0.61 [0.27, 1.36] 0.23 PASSION 8.9% 11.5% 0.75 [0.45, 1.27] 0.29 HORIZONS-AMI 5.6% 0.84 [0.60-1.17] 0.33 META-ANALYSIS 0.88 [0.68-1.11] 0.27 Adapted from Ziada KM et al. JACC CI Int 2011;4;39-41

Long-term (3-5 year) FU after DES vs. BMS in AMI TVR (N=6,026 pts) OR [95%CI] P DEDICATION 8.9% 19.8% 0.40 [0.25, 0.64] <0.01 PASEO 6.1% 21.1% 0.24 [0.11, 0.54] STRATEGY 10.3% 26.1% 0.33 [0.14, 0.75] 0.01 SESAMI 8.3% 16.0% 0.46 [0.23, 0.92] 0.03 MISSION 15.8% 0.54 [0.27, 1.09 0.09 TYPHOON 11.9% 21.5% 0.49 [0.30, 0.80] PASSION 7.7% 10.5% 0.73 [0.42, 1.26] 0.26 HORIZONS-AMI 12.5% 17.7% 0.67 [0.53-0.84] 0.001 META-ANALYSIS 0.50 [0.40-0.64] <0.001 Adapted from Ziada KM et al. JACC CI Int 2011;4;39-41

Should all pts with STEMI receive DES Should all pts with STEMI receive DES? Multivariable predictors of 12-month ischemic TLR among patients randomized to BMS Variable HR [95% CI] P-value Risk strata points Insulin-treated diabetes 3.12 [1.23, 7.87] 0.02 1 Baseline RVD ≤3.0 mm 2.89 [1.56, 5.34] 0.0007 Total lesion length ≥30 mm 2.49 [1.33, 4.68] 0.004 Stone GW et al. JACC 2010;56:1597-604

12 Month Ischemic TLR According to Risk Strata Bare metal stent Paclitaxel-eluting stent HR [95%] 0.39 [0.21, 0.74] Pint = 0.01 P=0.003 HR [95%] 0.58 [0.37, 0.92] HR [95%] 0.99 [0.43, 21.7] Ischemic TLR at 12 months (%) P=0.02 P=0.93 Low (score = 0) N = 947 (32.2%) Intermediate (score = 1) N = 1583 (53.9%) High (score = >2) N = 409 (13.9%) Risk score for restenosis Stone GW et al. JACC 2010;56:on-line

13 Month Binary Angiographic Restenosis According to Risk Strata Bare metal stent Paclitaxel-eluting stent HR [95% CI]= 0.42 [0.26, 0.66] RR [95% CI]= 0.44 [0.31, 0.63] P=0.0005 P<0.0001 RR [95% CI]= 0.44 [0.21, 0.95] Angiographic restenosis at 13 months (%) P=0.03 Low (score = 0) N = 422 (29.6%) Intermediate (score = 1) N = 722 (50.7%) High (score = >2) N = 280 (19.7%) Risk score for restenosis Stone GW et al. JACC 2010;56:on-line

► DES should be used as the default stent in. patients with ACS ► DES should be used as the default stent in patients with ACS - They are safe and effective in reducing clinical and angiographic restenosis in this setting ► If a DES is not used in ACS, there should be a good reason. Either: - BMS is likely to be as effective (non diabetic and RVD >3 mm and lesion length <30 mm), or - Adherence with 1-year of DAPT is uncertain Conclusions