Long-term safety and efficacy of zotarolimus-eluting and sirolimus-eluting stents in routine clinical care patients 36-month follow-up in the SORT OUT III trial Michael Maeng, Hans-Henrik Tilsted, Anne Kaltoft, Lisette O. Jensen, Henning Kelbæk, Anton B. Villadsen, Evald H. Christiansen, Lars R. Krusell, Peter R. Hansen, Knud N. Hansen, Jens Aarøe, Jan S. Jensen, Steen D. Kristensen, Hans E. Bøtker, Per Thayssen, Morten Madsen, Henrik T. Sørensen, Jan Ravkilde, Leif Thuesen, Jens F. Lassen, on behalf of the SORT OUT III investigators 1

18-Month Results. Lancet 2010;375:1090-1099 “The sirolimus-eluting stent is superior to the zotarolimus-eluting stent for patients receiving routine clinical care” 2

Endeavor vs. Cypher Six published randomized studies have uniformly shown that the zotarolimus-eluting Endeavor stent (END) is associated with increased rates of TLR as compared to the sirolimus-eluting Cypher (CYP) stent Very late stent thrombosis (VLST) is an increasingly important safety issue and this issue remains to be conclusively addressed with these DESs 3 3

Purpose To compare the 36-month clinical outcomes in routine clinical care (“all-comer”) patients randomized to END or CYP stent implantation 4

PCI organization in Denmark PCI center 100 US miles Population of 5.5 million inhabitants 5 high volume PCI centers 12-month dual anti-platelet therapy is recommended

Methods Inclusion criteria Indication for treatment with a DES Exclusion criteria Inability to provide informed consent Life expectancy < 1 year Allergy to aspirin or clopidogrel Participation in another trial Ascertained from 7

Endpoints Major adverse cardiac events (MACE) defined as a composite of cardiac mortality, myocardial infarction (MI), or target vessel revascularization (TVR) All cause mortality Cardiac mortality MI Definite stent thrombosis (ARC definition) TVR Target lesion revascularization (TLR)

Results 2,332 patients were enrolled Complete 36-month follow-up data for 2,323 patients 9 patients emigrated and were censored on the day of emigration 9

Selected Patient Characteristics END CYP No of patients 1162 1170 Age (yrs) 64 Male (%) 73 72 Diabetes mellitus (%) 15 14 Hypertension (%) 54 51 Lipid-lowering therapy (%) 70 68 Previous CABG (%) 7 Previous PCI (%) 21 17 Previous MI (%) 26 27

PCI Indication END CYP Stable angina (%) 53 51 NSTEMI/UAP (%) 38 6 9 Other (%) 4 3

MACE HR = 1.33 (1.04 – 1.69) P = 0.02 END : 12.9% CYP : 10.1% 13

All Cause Mortality HR = 1.25 (0.91 – 1.72) P = 0.17 END : 7.3% CYP : 5.9% 14 14

Cardiac Death HR = 1.02 (0.62 – 1.66) P = 0.95 END : 2.8% CYP : 2.8% 15

Myocardial Infarction HR = 1.19 (0.77 – 1.85) P = 0.44 END : 3.8% CYP : 3.3% 16

Definite Stent Thrombosis P = 0.61 CYP : 1.4% END : 1.1% 17

Target Vessel Revascularization HR = 1.40 (1.04 – 1.89) P = 0.02 END : 9.1% CYP : 6.7% 18

Target Lesion Revascularization HR = 1.82 (1.25 – 2.63) P = 0.002 END : 6.8% CYP : 3.9% 19 19

Landmark Analysis – Definite ST HR = 3.28 P = 0.038 Fisher’s exact test P = 0.0005 Cypher: ≈ 0.5% VLST/year END : 1.1% CYP : 1.1% CYP : 0.3% END : 0.0% 20

Conclusion The Cypher stent remains superior to the Endeavor stent at 36-month follow-up with regard to MACE, TVR and TLR

Conclusion The Cypher stent remains superior to the Endeavor stent at 36-month follow-up with regard to MACE, TVR and TLR In comparison to the Endeavor stent, the Cypher stent is associated with an increased risk of very late stent thrombosis (≈0.5%/year)

Thank you for your attention Conclusion The Cypher stent remains superior to the Endeavor stent at 36-month follow-up with regard to MACE, TVR and TLR In comparison to the Endeavor stent, the Cypher stent is associated with an increased risk of VLST (≈0.5%/year) Thank you for your attention