Xience V Everolimus-eluting Stent SPIRIT First 3-year Results SPIRIT II+III Meta-analysis Gregg W. Stone, MD Columbia University Medical Center The Cardiovascular Research Foundation

The Xience V SPIRIT Program (Results reported) SPIRIT First RCT vs. Vision SPIRIT II RCT vs. Taxus SPIRIT III RCT vs. Taxus Safety and performance N = 60 Europe PI: PW Serruys 3 year F/U completed First time report Clinical support for CE launch N = 300 EU, India, NZ PI: PW Serruys 1 year F/U completed Pivotal RCT with parallel registries N = 1,002 rand USA PI: GW Stone 9 month F/U completed 9 month pooled pt level meta-analysis First time report

SPIRIT First: Study Design XIENCE™ V Everolimus Eluting Coronary Stent (n=28) Single de novo Lesions 2.8 – 3.2 mm, 12 mm length n = 60 1 : ML VISION® Control (n=32) Prospective, randomized, single-blind trial Stent Size: 3.0 x 18 mm Clinical follow-up: 1, 6, 9, 12 months, 2, 3, 4, 5 years Angio and IVUS follow-up: 6 and 12 months Clopidogrel: 3 months Bailout only with BMS Only animal data on single stent available at the onset of the study Angiographic and IVUS core lab: Cardialysis Enrollment Complete: April 1, 2004 PI: Patrick Serruys

SPIRIT First: 3-year Follow-up Patient Population XIENCE™ V N=60 Control N=28 N=32 2: Bailout 1: Major Protocol Deviation* 1: Bailout Per-protocol Baseline N=27 N=29 1: Withdrew consent > 30d 1: Withdrew consent > 30d Per-protocol Three Year N=26 N=28 * Pt with heart failure waiting for a heart transplant

SPIRIT First: 3-year Results (non hierarchical event rates) % P=0.04 No MACE after 1-year in the XIENCE V group No stent thromboses in either group by protocol or ARC definitions MACE = Cardiac death, MI, or ischemic TLR

(1,302 randomized patients) SPIRIT II + III Pooled Meta-analysis Xience V vs. Taxus: Trial Descriptors (1,302 randomized patients) SPIRIT II SPIRIT III N rand pts, sites 300 pts at 31 sites 1002 pts at 65 sites Xience V : Taxus 3:1 (223:77) 2:1 (669:333) Geography Europe, Asia USA Ref ves dia (mm) 2.5 – 4.0 2.5 – 3.75 Lesion length (mm) ≤ 28 N lesions, vessels 1-2 lesions, 1/vessel Clinical FU w/i 1st yr 1, 6, 9, 12 mos Angio FU, completed 275/300 at 6 mos 436/564 at 8 mos This is the Bulleted List slide. To create this particular slide, click the NEW SLIDE button on your toolbar and choose the BULLETED LIST format. (Top row, second from left) The Sub-Heading and footnote will not appear when you insert a new slide. If you need either one, copy and paste it from the sample slide. If you choose not to use a Sub-Heading, let us know when you hand in your presentation for clean-up and we’ll adjust where the bullets begin on your master page. Also, be sure to insert the presentation title onto the BULLETED LIST MASTER as follows: Choose View / Master / Slide Master from your menu. Select the text at the bottom of the slide and type in a short version of your presentation title. Click the SLIDE VIEW button in the lower left hand part of your screen to return to the slide show. (Small white rectangle)

SPIRIT II + III Pooled Meta-analysis Baseline Features (1,302 randomized patients) Xience V (n=892 pts) Taxus (n=410 pts) Age (years) 62.9 ± 10.5 62.6 ± 10.1 Male 70.3% 68.2% Diabetes 27.9% 27.1% - treated with insulin 7.1% 5.7% Hypertension 74.0% 72.3% Hypercholesterolemia 72.8% 72.1% Current smoker 25.3% 23.8% Prior MI 23.7% 19.3% Unstable angina 20.8% 26.5% This is the Bulleted List slide. To create this particular slide, click the NEW SLIDE button on your toolbar and choose the BULLETED LIST format. (Top row, second from left) The Sub-Heading and footnote will not appear when you insert a new slide. If you need either one, copy and paste it from the sample slide. If you choose not to use a Sub-Heading, let us know when you hand in your presentation for clean-up and we’ll adjust where the bullets begin on your master page. Also, be sure to insert the presentation title onto the BULLETED LIST MASTER as follows: Choose View / Master / Slide Master from your menu. Select the text at the bottom of the slide and type in a short version of your presentation title. Click the SLIDE VIEW button in the lower left hand part of your screen to return to the slide show. (Small white rectangle) There were no significant between group differences

SPIRIT II + III Pooled Meta-analysis Angiographic Characteristics (1,501 lesions in 1,302 randomized patients) Xience V (n=1028 lsns) Taxus (n=473 lsns) LAD 41.1% 43.8% LCX 28.0% 26.4% RCA 30.7% 29.6% LMCA 0.1% 0.2% RVD (mm) 2.75 ± 0.47 2.77 ± 0.48 MLD (mm) 0.88 ± 0.43 0.89 ± 0.41 % DS 67.7 ±13.6 67.5 ±13.6 Lsn length (mm) 14.3 ± 5.7 14.5 ± 5.9 Lesion location This is the Bulleted List slide. To create this particular slide, click the NEW SLIDE button on your toolbar and choose the BULLETED LIST format. (Top row, second from left) The Sub-Heading and footnote will not appear when you insert a new slide. If you need either one, copy and paste it from the sample slide. If you choose not to use a Sub-Heading, let us know when you hand in your presentation for clean-up and we’ll adjust where the bullets begin on your master page. Also, be sure to insert the presentation title onto the BULLETED LIST MASTER as follows: Choose View / Master / Slide Master from your menu. Select the text at the bottom of the slide and type in a short version of your presentation title. Click the SLIDE VIEW button in the lower left hand part of your screen to return to the slide show. (Small white rectangle) QCA There were no significant between group differences

SPIRIT II + III Pooled Meta-analysis Late Loss mm Diff [95%CI] -0.19 [-0.25,-0.13] P<0.0001 Diff [95%CI] -0.11 [-0.17,-0.06] P=0.0004 ±0.48 ±0.36 ±0.44 ±0.37 This is the Bulleted List slide. To create this particular slide, click the NEW SLIDE button on your toolbar and choose the BULLETED LIST format. (Top row, second from left) The Sub-Heading and footnote will not appear when you insert a new slide. If you need either one, copy and paste it from the sample slide. If you choose not to use a Sub-Heading, let us know when you hand in your presentation for clean-up and we’ll adjust where the bullets begin on your master page. Also, be sure to insert the presentation title onto the BULLETED LIST MASTER as follows: Choose View / Master / Slide Master from your menu. Select the text at the bottom of the slide and type in a short version of your presentation title. Click the SLIDE VIEW button in the lower left hand part of your screen to return to the slide show. (Small white rectangle)

SPIRIT II + III Pooled Meta-analysis Binary Restenosis % HR [95%CI] 0.53 [0.30,0.95] P=0.039 HR [95%CI] 0.39 [0.17,0.86] P=0.02 This is the Bulleted List slide. To create this particular slide, click the NEW SLIDE button on your toolbar and choose the BULLETED LIST format. (Top row, second from left) The Sub-Heading and footnote will not appear when you insert a new slide. If you need either one, copy and paste it from the sample slide. If you choose not to use a Sub-Heading, let us know when you hand in your presentation for clean-up and we’ll adjust where the bullets begin on your master page. Also, be sure to insert the presentation title onto the BULLETED LIST MASTER as follows: Choose View / Master / Slide Master from your menu. Select the text at the bottom of the slide and type in a short version of your presentation title. Click the SLIDE VIEW button in the lower left hand part of your screen to return to the slide show. (Small white rectangle)

SPIRIT II + III Pooled Meta-analysis Ischemic TLR (9 months) 6 XIENCE V TAXUS 5.1% 5 4 Ischemic TLR (%) 3 2.4% 2 HR [95% CI] 0.47 [0.26,0.87] p=0.01 1 3 6 9 Time in months Number at risk XIENCE 892 879 867 793 TAXUS 408 397 389 349

SPIRIT II + III Pooled Meta-analysis Stent Thrombosis (9 months) 4 XIENCE V TAXUS 3 Stent thrombosis (%) 2 HR [95% CI] 1.82 [0.20,16.31] p=0.59 1 0.45% 0.25% 3 6 9 Time in months Number at risk XIENCE 892 882 877 811 TAXUS 408 401 398 368 Protocol definition = ACS + angiographic ST or unexplained death or AMI (STE or Q) in TL distribution w/i 30d

SPIRIT II + III Pooled Meta-analysis Cardiac Death (9 months) 4 XIENCE V TAXUS 3 HR [95% CI] 0.45 [0.09,2.24] p=0.32 Cardiac Death (%) 2 1 0.76% 0.35% 3 6 9 Time in months Number at risk XIENCE 892 884 879 814 TAXUS 408 401 398 368

SPIRIT II + III Pooled Meta-analysis Myocardial Infarction (9 months) 4 HR [95% CI] 0.62 [0.28,1.35] p=0.22 XIENCE V TAXUS 3 2.7% MI (%) 2 1.7% 1 3 6 9 Time in months Number at risk XIENCE 888 876 870 801 TAXUS 407 392 389 360

SPIRIT II + III Pooled Meta-analysis Cardiac Death or MI (9 months) 4 XIENCE V TAXUS 3.2% 3 p=0.19 2.1% Cardiac Death or MI (%) 2 1 3 6 9 Time in months Number at risk XIENCE 888 876 870 801 TAXUS 407 392 389 360

SPIRIT II + III Pooled Meta-analysis MACE (9 months) 10 XIENCE V TAXUS 8.0% 8 HR [95% CI] 0.50 [0.31,0.81] p=0.004 6 Ischemic MACE (%) 4.1% 4 2 3 6 9 Time in months Number at risk XIENCE 888 871 858 783 TAXUS 407 388 380 341 MACE = Cardiac death, MI, or ischemic TLR

SPIRIT II + III Pooled Meta-analysis Conclusions Compared to the Taxus paclitaxel- eluting stent, the Xience V everolimus- eluting stent results in: Reduced late loss and binary restenosis Reduced target lesion revascularization Similar rates of death, MI and stent thrombosis Fewer major adverse cardiac events