for the SPIRIT IV Investigators A Large-Scale Randomized Comparison of Everolimus-Eluting and Paclitaxel-Eluting Stents: Three-Year Clinical Outcomes from the SPIRIT IV Trial Gregg W. Stone, MD Manejeh Yaqub, MD; Poornima Sood, MD, MBA; Ali Rizvi, MD; William Newman, MD; Kourosh Mastali, MD; John C. Wang, MD; Ronald E. Caputo, MD; Kyoko Hattori, RN, BSN; Xiaolu Su, MS; Charles A. Simonton, MD; Alexandra J. Lansky, MD; Donald E. Cutlip, MD; Krishnankutty Sudhir MD, PhD; and Dean J. Kereiakes, MD for the SPIRIT IV Investigators

Disclosures Gregg W. Stone, MD Consultant to Abbott Vascular, Boston Scientific and Medtronic

Background In SPIRIT IV, the largest clinical trial to date comparing 2 DES, treatment with the XIENCE V everolimus-eluting stent compared to the TAXUS Express paclitaxel-eluting stent resulted in significantly reduced 1-year and 2-year rates of target lesion failure (TLF), ischemia-driven TLR, MI and stent thrombosis. Whether the benefits of XIENCE V compared to TAXUS Express are sustained at 3 years has not been reported.

Study Algorithm XIENCE V TAXUS 3690 pts enrolled at 66 U.S. sites RVD ≥2.5 mm - ≤3.75 mm; Lesion length ≤28 mm Max. 3 lesions with a maximum of 2 per epicardial vessel Pre-rand: ASA ≥300 mg, clopidogrel ≥300 mg load unless on chronic Rx Randomized 2:1 XIENCE V:TAXUS Express2 Stratified by diabetes and presence of complex lesions Pre-dilatation mandatory Everolimus-eluting XIENCE V Paclitaxel-eluting TAXUS Aspirin ≥80 mg QD for 5 years; clopidogrel 75 mg QD for at least 12 mos (if not at high risk for bleeding) Clinical f/u only: 1, 6, 9 months and yearly for 1-5 years

Major Exclusion Criteria Any target lesion or vessel meets any of the following: Left main or ostial LAD/LCX In or distal to a bypass graft conduit Bifurcation with sidebranch diameter ≥2 mm AND ostial DS >50% OR requiring pre-dilatation Total occlusion, thrombus, restenotic, excessive tortuosity, angulation or heavy calcification Prior coronary brachytherapy High probability of additional PCI within 9 months

Patient Flow and Follow-up XIENCE V (N=2411) Randomized (N=3687) (N=2458) TAXUS (N=1229) 1-Year Follow-up* (N=3609; 97.9%) Lost to f/u = 39 Withdrawal = 8 Other = 0 22 = Lost to f/u 8 = Withdrawal 1 = Other Enrolled (N=3690) 3 = Randomization errors TAXUS (N=1198) 2-Year Follow-up* (N=3539; 96.0%) (N=2371) TAXUS (N=1168) Lost to f/u = 24 Withdrawal = 15 Other = 1 23 = Lost to f/u 7 = Withdrawal 3-Year Follow-up* (N=3506; 95.1%) (N=2348) TAXUS (N=1158) Lost to f/u = 9 Withdrawal = 11 Other = 3 4 = Lost to f/u 6 = Withdrawal *F/U window: ± 28 days

Baseline Demographics XIENCE V 2458 pts TAXUS 1229 pts P value Age (in years) 63.3 ± 10.5 63.3 ± 10.2 0.80 Male (%) 67.7 67.8 1.00 Hypertension (%) 77.4 76.1 0.41 Hypercholesterolemia (%) 75.5 0.74 Diabetes mellitus (%) 32.0 32.5 0.79 - Insulin requiring (%) 8.5 9.7 0.24 Current smoker (%) 21.9 22.4 0.70 Prior MI (%) 21.1 19.9 Unstable angina (%) 27.7 28.9 0.46

Baseline Angiography XIENCE V 3142 lesions TAXUS 1585 lesions P value Lesion location LAD 40.5% 39.8% 0.68 LCX 24.2% 25.4% 0.35 RCA 35.4% 34.8% LMCA 0.0% - QCA RVD (mm) 2.75 ± 0.48 2.75 ± 0.46 0.59 MLD (mm) 0.75 ± 0.38 0.76 ± 0.39 0.36 % DS 72.3 ± 12.6 72.0 ± 12.8 0.44 Lsn length (mm) 14.8 ± 6.7 14.5 ± 6.6 0.24

Antiplatelet Agent Utilization XIENCE V 2458 pts TAXUS 1229 pts P value Aspirin - At 1 year 97.0% 96.8% 0.76 - At 2 years 96.0% 96.2% 0.85 - At 3 years 94.5% 94.9% 0.74 Thienopyridine 94.0% 93.8% 0.82 70.2% 68.1% 0.22 60.3% 1.00 T7

Target Lesion Failure Through 3 Years Target lesion failure (%) 25 XIENCE V (n=2458) TAXUS Express (n=1229) 20 HR [95%CI] = 0.78 [0.63, 0.97] p=0.004 HR [95%CI] = 0.71 [0.56, 0.90] p=0.02 p=0.001 HR [95%CI] = 0.61 [0.46, 0.81] 15 11.7% Target lesion failure (%) 9.9% Δ 2.5% 10 Δ 2.9% 6.7% 9.2% Δ 2.7% 7.0% 5 4.0% 3 6 9 12 15 18 21 24 27 30 33 36 Months Number at risk XIENCE V 2458 2390 2364 2323 2281 2238 2212 2187 2162 2132 2116 2095 2074 TAXUS 1229 1166 1138 1119 1095 1069 1060 1049 1029 1019 1008 994 979 TLF (primary endpoint at 1 year) = cardiac death, target vessel MI, or ischemia-driven TLR

Multivariable Predictors of TLF at 3 Years Variables Odds Ratio [95% CI] P Value Presence of thrombus (Yes vs No) 0.18 [0.04, 0.75] 0.02 RVD (per 1 mm) 0.60 [0.47, 0.78] 0.0001 ACC/AHA lesion class (A or B1 vs B2 or C) 0.67 [0.53, 0.84] 0.0006 Treatment (XIENCE V vs TAXUS) 0.74 [0.58, 0.93] 0.009 Diabetes requiring treatment 1.43 [1.13, 1.82] 0.003 Numbers of diseased vessels (≥2 vs 1) 1.29 [1.03, 1.63] 0.03

Ischemia-Driven TLR Through 3 Years Ischemia-driven TLR (%) 12 XIENCE V (n=2458) HR [95%CI] = 0.78 [0.60, 1.01] TAXUS Express (n=1229) HR [95%CI] = 0.65 [0.49, 0.87] 10 p=0.06 p=0.003 7.8% HR [95%CI] = 0.51 [0.35, 0.73] 8 6.9% Δ 1.6% p=0.0002 Ischemia-driven TLR (%) 6 Δ 2.4% 4.6% 6.2% 4 4.5% Δ 2.4% 2 2.2% 3 6 9 12 15 18 21 24 27 30 33 36 Months Number at risk XIENCE V 2458 2420 2395 2355 2314 2271 2248 2225 2202 2172 2156 2136 2116 TAXUS 1229 1186 1159 1140 1116 1090 1081 1070 1051 1041 1033 1019 1005 Major secondary endpoint at 1 year

All-cause Death Through 3 Years 8 XIENCE V (n=2458) TAXUS Express (n=1229) HR [95%CI] = 0.66 [0.48, 0.93] 7 p=0.02 6 5.1% HR [95%CI] = 0.80 [0.52, 1.25] 5 p=0.33 Death (%) HR [95%CI] = 0.86 [0.46, 1.62] Δ 1.9% 4 2.7% 3 p=0.64 Δ 0.6% 3.2% 2 1.2% 2.1% Δ 0.2% 1 1.0% 3 6 9 12 15 18 21 24 27 30 33 36 Months Number at risk XIENCE V 2458 2431 2417 2392 2362 2335 2323 2315 2302 2279 2272 2261 2250 TAXUS 1229 1207 1199 1187 1169 1147 1143 1139 1127 1118 1113 1102 1089

Target Vessel MI Through 3 Years 15 XIENCE V (n=2458) TAXUS Express (n=1229) 12 HR [95%CI] = 0.67 [0.46, 0.97] HR [95%CI] = 0.69 [0.46, 1.03] 9 p=0.03 HR [95%CI] = 0.65 [0.42, 1.02] Target Vessel MI (%) p=0.07 6 p=0.06 4.0% 3.4% 2.9% Δ 1.3% 3 Δ 1.1% Δ 1.0% 2.7% 2.3% 1.9% 3 6 9 12 15 18 21 24 27 30 33 36 Months Number at risk XIENCE V 2458 2393 2378 2350 2319 2292 2277 2266 2251 2227 2218 2207 2194 TAXUS 1229 1180 1167 1155 1137 1116 1110 1106 1093 1084 1074 1062 1048

All Death or MI Through 3 Years 2 4 6 8 10 12 14 3 9 15 18 21 24 27 30 33 36 XIENCE V (n=2458) TAXUS Express (n=1229) HR [95%CI] = 0.67 [0.52, 0.85] p=0.001 HR [95%CI] = 0.77 [0.57, 1.04] 9.1% HR [95%CI] = 0.72 [0.50, 1.03] p=0.08 Δ 3.2% All Death or MI (%) 5.9% p=0.07 Δ 1.4% 4.0% 5.9% Δ 1.1% 4.5% 2.9% Months Number at risk XIENCE V 2458 2392 2378 2350 2319 2291 2276 2264 2247 2223 2214 2202 2187 TAXUS 1229 1179 1165 1153 1136 1114 1108 1104 1090 1080 1070 1057 1043

Clinical Outcomes at 3 Years XIENCE V (N=2458) TAXUS (N=1229) HR [95%CI] Log-rank P value Death, all 3.2% 5.1% 0.66 [0.48, 0.93] 0.02 - Cardiac 1.4% 1.9% 0.76 [0.44, 1.30] 0.31 - Non cardiac 1.8% 3.3% 0.61 [0.40, 0.93] MI, target vessel 2.7% 4.0% 0.67 [0.46, 0.97] 0.03 MI, all 3.0% 4.6% 0.65 [0.46, 0.93] - Q-wave 0.3% 0.9% 0.27 [0.10, 0.73] 0.005 - Non Q-wave 2.8% 3.9% 0.72 [0.49, 1.05] 0.08 ID-TLR 6.2% 7.8% 0.78 [0.60, 1.01] 0.06 PCI 5.6% 7.4% 0.74 [0.57, 0.97] CABG 0.7% 0.89 [0.41, 1.92] 0.76 K-M curves Rates (%) are Kaplan-Meier estimates 16

Stent Thrombosis (Protocol Definition)* 6 XIENCE V (n=2458) TAXUS Express (n=1229) 5 HR [95%CI] = 0.40 [0.22, 0.75] 4 p=0.02 HR [95%CI] = 0.42 [0.20, 0.92] p=0.003 Stent thrombosis (%) 3 p=0.01 HR [95%CI] = 0.30 [0.11, 0.82] 1.89% 2 1.17% Δ 1.12% 0.82% 1 Δ 0.71% Δ 0.57% 0.25% 0.77% 0.46% 3 6 9 12 15 18 21 24 27 30 33 36 Months Number at risk XIENCE V 2458 2427 2413 2387 2358 2331 2319 2311 2295 2272 2264 2254 2242 TAXUS 1229 1199 1189 1178 1160 1140 1134 1130 1118 1109 1101 1089 1076 *ACS + angiographic thrombus, or unexplained death or STEMI/Q-wave MI in TL distribution within 30 days

Stent Thrombosis (Protocol Definition)* Early (0 – 30 days) Late (>30 days – 1 year) Very Late (>1 year) 0.08 XIENCE V N=2458 0.79% p=0.004 TAXUS N=1229 1.99% Stent thrombosis (%) *ACS + angiographic thrombus, or unexplained death or STEMI/Q-wave MI in TL distribution within 30 days

Stent Thrombosis (ARC Def or Prob) 4 XIENCE V (n=2458) TAXUS Express (n=1229) HR [95%CI] = 0.36 [0.18, 0.72] 3 HR [95%CI] = 0.36 [0.17, 0.79] HR [95%CI] = 0.27 [0.11, 0.67] p=0.003 p=0.008 Stent thrombosis (%) 2 p=0.003 1.60% 1.24% 1.06% Δ 1.01% 1 Δ 0.82% Δ 0.77% 0.59% 0.42% 0.29% 3 6 9 12 15 18 21 24 27 30 33 36 Months Number at risk XIENCE V 2458 2427 2413 2387 2358 2331 2319 2311 2296 2272 2263 2254 2242 TAXUS 1229 1196 1186 1175 1157 1137 1131 1127 1115 1106 1098 1086 1073

Stent Thrombosis (ARC Def or Prob) Early (0 – 30 days) Late (>30 days – 1 year) Very Late (>1 year) XIENCE V N=2458 0.13 0.62% p=0.004 TAXUS N=1229 1.73% Stent thrombosis (%)

SPIRIT IV: 11 Subgroups Examined Age ≥ 65 (n=1578) Diabetes (n=1102) Age < 65 (n=1928) No diabetes (n=2400) Male (n=2390) Lesion number = Single (n=2633) Female (n=1116) Lesion number = Multi (≥2) (n=873) Hypertension* (n=2705) Lesion length > median (13.3 mm; n=1308) No hypertension (n=796) Lesion length ≤ median (13.3 mm; n=1311) Hypercholesterolemia* (n=2636) RVD > median (2.75 mm; n=1314) No hypercholesterolemia (n=816) RVD ≤ median (2.75 mm; n=1312) BMI ≥ 30 (n=1707) Bailout (n=305) BMI < 30 (n=1799) No bailout (n=3201) Stable angina (n=2030) No stable angina (n=1412) RVD and lesion length from the single lesion treated subgroup. * Requiring medication

SPIRIT IV Subgroup Analysis: TLF at 3 Years Xience V (%) Taxus Relative Risk (95% CI) P interaction All randomized (n=3687) 9.5 11.9 0.80 [0.65, 0.97] — Age ≥ 65 yrs (n=1578) 9.6 10.4 0.93 [0.68, 1.26] 0.20 Age < 65 yrs (n=1928) 9.4 13.2 0.71 [0.55, 0.93] Male (n=2390) 11.4 0.84 [0.66, 1.07] 0.46 Female (n=1116) 9.3 12.9 0.72 [0.51, 1.01] Hypertension* (n=2705) 10.0 12.3 0.82 [0.65, 1.02] 0.65 No hypertension (n=796) 7.6 10.6 0.72 [0.46, 1.13] Hypercholesterolemia* (n=2636) 9.0 11.7 0.77 [0.61, 0.98] 0.54 No hypercholesterolemia (n=816) 11.0 12.2 0.90 [0.60, 1.34] BMI ≥ 30 (n=1707) 10.1 0.86 [0.65, 1.14] BMI < 30 (n=1799) 8.9 12.1 0.74 [0.56, 0.98] Stable angina (n=2030) 12.7 0.73 [0.56, 0.94] 0.32 No stable angina (n=1412) 11.2 0.90 [0.65, 1.23] EES better PES better TLF = cardiac death, target vessel MI, or ischemia-driven TLR; 2 Years = 730 ± 28 days; *Requiring medication

SPIRIT IV Subgroup Analysis: TLF at 3 Years Xience V (%) Taxus Relative Risk (95% CI) P interaction All randomized (n=3687) 9.5 11.9 0.80 [0.65, 0.97] — Single lesion treated (n=2633) 8.2 10.6 0.78 [0.60, 0.99] 0.74 Multiple lesions (≥2) treated (n=873) 13.4 15.9 0.84 [0.60, 1.18] RVD > 2.75 mm (n=1314) 6.7 8.7 0.77 [0.52, 1.14] 1.00 RVD ≤ 2.75 mm (n=1312) 9.8 12.6 0.78 [0.56, 1.07] Lesion length > 13.3 mm (n=1308) 13.1 0.66 [0.47, 0.92] 0.19 Lesion length ≤ 13.3 mm (n=1311) 7.8 8.5 0.92 [0.63, 1.33] Bailout (n=305) 12.2 21.7 0.56 [0.33, 0.96] 0.18 No bailout (n=3201) 9.2 11.2 0.83 [0.67, 1.02] Diabetes (n=1102) 12.4 0.95 [0.68, 1.31] 0.21 No diabetes (n=2400) 11.4 0.72 [0.56, 0.93] EES better PES better TLF = cardiac death, target vessel MI, or ischemia-driven TLR; 2 Years = 730 ± 28 days Single lesion treated data are used for RVD & lesion length subgroup analyses

SPIRIT IV 3-Year Conclusions In the large-scale, prospective, multicenter, randomized SPIRIT IV trial, the benefits of the XIENCE V everolimus-eluting stent compared to the TAXUS Express paclitaxel-eluting stent present at 1 year and 2 years were sustained at 3 years

SPIRIT IV 3-Year Conclusions With increasing duration of follow-up, the following insights have emerged: Significant differences in all-cause mortality are apparent at 3 years favoring XIENCE V Stent thrombosis rates continue to diverge favoring XIENCE V, with a 1% absolute difference in stent thrombosis present at 3 years The differences between the 2 stent types in ischemia-driven TLR have narrowed, and are no longer significant at 3 years Consistent relative reductions in TLF with EES were present in 11 pre-specified subgroups, including multiple lesions, long lesions and small vessels Non-significantly different rates of TLF were present in pts with diabetes, vs a 28% reduction in TLF in pts without diabetes