Final 5 year results from the all-comer COMPARE trial: a prospective randomized comparison between Xience-V and Taxus Liberté TCT 2013 San Francisco Pieter Smits, MD, PhD, FESC Kaiyum Sheikjoesoef, Martin van de Ent, Jochem Wassing, Georgios Vlachojannis, Elvin Kedhi, Carlos van Mieghem, Eugene MacFadden Maasstad Hospital Rotterdam, The Netherlands

Disclosure Statement of Financial Interest Grant/Research Support Consulting Fees/Honoraria Major Stock Shareholder/Equity Royalty Income Ownership/Founder Intellectual Property Rights Other Financial Benefit Abbott Vascular, St. Jude, Terumo Abbott Vascular, St. Jude None Within the past 12 months, I or my spouse/partner have had a financial interest/arrangement or affiliation with the organization(s) listed below. Affiliation/Financial RelationshipCompany Thanks to: CEC & Core Lab & Statistics Cardialysis, Rotterdam Claudia van Vliet Research coordinator Maasstad Cardiovascular Research

COMPARE PI: dr. P. C. Smits N = 1800 patients Single center Primary endpoint: Primary endpoint: All death, non fatal MI and TVR at 12 months Secondary endpoints: Cardiac death, non fatal MI and ID-TLR Stent thrombosis Primary endpoint: Primary endpoint: All death, non fatal MI and TVR at 12 months Secondary endpoints: Cardiac death, non fatal MI and ID-TLR Stent thrombosis 30d 6mo 4yr 3yr 2yr 12mo 5yr Clinical/MACE Taxus Liberté n = 903 pts Taxus Liberté n = 903 pts Xience-V n = 897 pts Xience-V Minimal in-exclusion criteria DAPT for 12 months DAPT for 12 months No cardiogenic shock No cardiogenic shock Life expectancy > 5 years Life expectancy > 5 years Minimal in-exclusion criteria DAPT for 12 months DAPT for 12 months No cardiogenic shock No cardiogenic shock Life expectancy > 5 years Life expectancy > 5 years Prim endpoint 1:1 randomization Single center – All-comer – Superiority design (delta 5%, Power 85%) TCT 2013

STEMI 25 % Calcification 34 % Multistenting 62 % Ostial 19 % Thrombus 24 % CTO 4 % NSTEMI 23 % Multivessel 27 % Saphenous graft 2 % Bifurcation 10 % Diabetes 18 % Chronic renal failure 3 % Left main 2 % Direct stenting 34 % COMPARE TRIAL “REAL WORLD”

Randomized(N=1800) XIENCE V (N=897) 1-Year Follow-up (N=1797; 99.8%) Lost to f/u = 1 Lost to f/u = 2 2-Year Follow-up (N=1795; 99.7%) Taxus Liberté (N=902) (N=903) (N=900) XIENCE V (N=895) Lost to f/u = 0Lost to f/u = 2 No study stent = 6 No study stent = 4 3-Year Follow-up (N=1792; 99.6%) Lost to f/u = 2Lost to f/u = 1 Taxus Liberté (N=899) XIENCE V (N=893) 5-Year Follow-up (N=1791;99.5%) Lost to f/u = 1Lost to f/u = 0 Taxus Liberté (N=899) XIENCE V (N=892)

COMPARE Dual Anti Platelet Therapy P = 0.02 NS *

Final 5 year Primary Endpoint Result MACE (all death, non-fatal MI and TVR) P = (log-rank test) Δ 4.7 % Taxus Xience RR = 0.66 ( ) Δ 2.9 % Δ 6.1 % 18.4 % 12.3 % RR = 0.68 ( ) RR = 0.67 ( ) 13.7 % 9.0 % 9.1 % 6.2 % P=0.023 P= % 18.4 % Δ 6.7 % RR = 0.73 ( ) P= P=0.0003

Safety (Death or 5 yr 14.3 % Taxus Xience P = (log-rank test) Δ 4.5 % Δ 3.5 % Δ 2.4 % 10.5 % 7.0 % RR = 0.69 (0.53 – 0.89) P = RR = 0.67 (0.49 – 0.91) P = 0.01 RR = 0.61 (0.40 – 0.91) P = % Δ 5.5 % RR = 0.72 (0.59 – 0.89) P = % 7.0 % 4.6 % 14.6 %

First 5 yr 9.7 % Taxus Xience P = (log-rank test) Δ 4.9 % Δ 4.4 % Δ 3.5 % 8.1 % 6.0 % RR = 0.49 (0.35 – 0.70) P < RR = 0.46 (0.30 – 0.68) P < RR = 0.41 (0.25 – 0.67) P = % Δ 4.0 % RR = 0.65 (0.48 – 0.87) P = % 3.7 % 2.5 % 7.4 %

First clinically indicated 5 yr 7.4 % Taxus Xience P = (log-rank test) Δ 3.7 % Δ 3.4 % Δ 3.1 % 6.1 % 4.7 % RR = 0.50 (0.33 – 0.74) P = RR = 0.44 (0.27 – 0.70) P = RR = 0.34 (0.18 – 0.61) P = % Δ 3.3 % RR = 0.60 (0.42 – 0.86) P = % 2.7 % 1.6 % 5.0 %

Target lesion 5 yr 12.8 % Taxus Xience P = (log-rank test) Δ 4.4 % Δ 3.7 % Δ 3.3 % 10.4 % 7.8 % RR = 0.65 (0.49 – 0.86) P = RR = 0.64 (0.47 – 0.88) P = RR = 0.57 (0.39 – 0.84) P = % Δ 4.5 % RR = 0.71 (0.56 – 0.90) P = % 6.7 % 4.5 % 11.4 %

Target Vessel 5 yr 14.5 % Taxus Xience P = (log-rank test) Δ 5.4 % Δ 4.1 % Δ 3.2 % 11.6 % 8.3 % RR = 0.63 (0.49 – 0.82) P = RR = 0.64 (0.48 – 0.86) P = RR = 0.61 (0.43 – 0.88) P = % Δ 5.2 % RR = 0.71 (0.57 – 0.88) P = % 7.5 % 5.1 % 12.6 %

First Myocardial 5 yr 9.9 % Taxus Xience P = (log-rank test) Δ 4.8 % Δ 3.9 % Δ 2.6 % 7.8 % 5.4 % RR = 0.52 (0.37 – 0.73) P = RR = 0.50 (0.34 – 0.75) P = RR = 0.51 (0.32 – 0.82) P = % Δ 4.5 % RR = 0.61 (0.45 – 0.82) P = % 3.9 % 2.8 % 7.0 %

First def/prob Stent 5 yr (Definite / Probable according to ARC) 4.9 % 1.3 % Taxus Xience P = (log-rank test) Δ 3.6 % Δ 3.0 % Δ 1.9 % 3.9 % 0.9 % 2.6 % 0.7 % RR = 0.27 ( ) P < RR = 0.23 ( ) P < RR = 0.26 ( ) P = % 3.1 % Δ 2.8 % RR = 0.53 (0.34 – 0.83) P = 0.005

XIENCE V N=897 TAXUS N=903 Stent thrombosis (%) 3.1 % 5,9% p=0.03 Def / Prob Stent Thrombosis (ARC Definition)* Early (0 – 30 days) Late (>30 days – 1 year ) Very Late ( year)** *Definite or Probable per ARC definition **Categorical data, 365 ± 28 days

First Definite Stent 5 yr (Definite according to ARC) 3.5 % 1.1 % Taxus Xience P = 0.03 (log-rank test) Δ 2.4 % Δ 1.9 % Δ 1.6 % 2.7 % 0.8 % 2.0 % 0.4 % RR = 0.31 (0.16 – 0.64) P = RR = 0.29 (0.13 – 0.68) P = RR = 0.22 (0.08 – 0.66) P = % 2.2 % Δ 1.8 % RR = 0.56 (0.33 – 0.96) P = 0.03

All 5 yr 5.2 % Taxus Xience P = 0.38 (log-rank test) 3.0 % 1.7 % 10.3 % RR = 0.87 (0.67 – 1.17) P = % 3.3 % 2.0 % 9.0 %

Non Target Vessel 5 yr Taxus Xience P = 0.73 (log-rank test) 8.1 % 8.6 %

Major Adverse Cardiac Events at 1800 days in Subgroups No. Events (%) Everolimus better Paclitaxel better Everolimus Paclitaxel Relative Risk 95% CI p value for interaction p-value No Diabetes 127/744 (17%) 168/730 (23%) ( ) Diabetes 38 /153 (25%) 59/172 (34%) ( ) Woman 45/278 (16%) 75/249 (30%) ( ) Men 120/619 (19%) 152/654 (23%) ( ) No ACS 76/356 (21%) 96/369 (26%) ( ) ACS 89/541 (16%) 131/534 (25%) ( ) Single Vessel 119/653 (18%) 145/662 (22%) ( ) Multivessel 46/242 (19%) 81/239 (34%) ( ) Restenosis 9/30 (30%) 14/28 (50%) ( ) De novo 156/867 (18%) 213/875 (24%) ( ) No acute MI 130/657 (20%) 178/687 (26%) ( ) Acute MI 35/240 (15%) 49/212 (23%) ( ) No prox LAD 110/646 (17%) 161/671 (24%) ( ) Proximal LAD 47/233 (20%) 57/210 (27%) ( ) Lesion <20 mm 117/607 (19%) 165/640 (26%) ( ) Lesion ≥ 20 mm 48/290 (17%) 62/263 (24%) ( ) RVD ≥ 2.75 mm 84/438 (19%) 117/462 (25%) ( ) RVD < /458 (18%) 110/441 (25%) ( ) Overall 165/897 (18%) 227/903 (25%) ( )

What if Xience was used in the Syntax trial ? 485 pts in COMPARE were treated for LM and / or MVD 223 pts. Xience 222 pts. Taxus

LM - Multivessel PCI subgroup MACE Syntax ≤ 22; Syntax 23-32; Syntax ≥ 33 P Logrank = pts Taxus 156 pts Xience P Logrank = pts Taxus 54 pts Xience P Logrank = pts Taxus 22 pts Xience 45.5 % 40.9 % 29.5 % 36.4 % 18.6 % 18.0 % RR 0.80 ( ) RR 0.45 ( ) p = RR 0.61 ( ) p = pts excluded for SYNTAX analysis (post CABG)

Compare versus Syntax trial (MACE) Syntax ≤ 22 subgroup N = 302 pts. P Logrank = % 18.0 % RR 0.61 ( ), p = pts excluded for SYNTAX analysis (post CABG) 24.7 % 30.8 % N = 574 pts. P Logrank =0.12 COMPARE trial SYNTAX trial RR 0.77 ( ), p = 0.06

Compare versus Syntax trial (MACE) Syntax 23 – 32 subgroup N = 122 pts. P Logrank = % 18.6 % RR 0.45 ( ), p = pts excluded for SYNTAX analysis (post CABG) 22.1 % 34.4 % N = 610 pts. P Logrank =0.001 COMPARE trial SYNTAX trial RR 0.61 ( ), p = 0.003

Compare versus Syntax trial (MACE) Syntax ≥ 33 subgroup N = 44 pts. P Logrank = % 36.4 % RR 0.80 ( ) 19 pts excluded for SYNTAX analysis (post CABG) 22.4 % 42.2 % N = 605 pts. P Logrank < COMPARE trial SYNTAX trial RR 0.51 ( ), p < 0.001

Conclusions Xience stent remained superior compared to Taxus Liberte up to 5 year for MACE, MI, TVR, TLR and ST Subgroup analysis, though P-value for interaction was not significant (p=0.07), indicate that LM and/or multivessel PCI with Xience is highly superior compared to Taxus in patients with low and intermediate SYNTAX scores 5 year follow up with Xience in an all-comer population shows an annual 3.1 % MACE, 1.9% TVF and 0.38% def. ST rate after 1 year, indicating room for further improvement with new devices like BVS