euro PCR

Randomized comparison of a sirolimus-eluting stent with a biolimus-eluting stent in patients treated with PCI: the SORT OUT VII trial

Lisette Okkels Jensen, Per Thayssen, Michael Maeng, Jan Ravkilde, Lars Krusell, Hans-Henrik Tilsted, Anders Junker, Christian Juhl Terkelsen, Karsten Tange Veien, Anne Kaltoft, Anton Boel Villadsen, Jens Aaroe, Kl ára Berencsi, Svend Eggert Jensen, Knud Nørregaard Hansen, Steen Dalby Kristensen, Morten Madsen, Hans Erik Bøtker Henrik Steen Hansen, Bent Raungaard, Jens Flensted Lassen, Ev ald Høj Christiansen

Odense University Hospital, Aarhus University Hospital, Aalborg University Hospital - DENMARK

euro PCR 2015

Potential conflicts of interest

Speaker's name: Lisette Okkels Jensen



I have the following potential conflicts of interest to report:

Honorarium: ABBOTT VASCULAR, ASTRAZENECA, BIOTRONIK, ST. JUDE MEDICAL Institutional grant/research support: BIOSENSORS INTERNATIONAL, BIOTRONIK, ST. JUDE MEDICAL, TERUMO SORT OUT VII 1Y

Background

 Drug-eluting stents have reduced the risk of in-stent restenosis.

Compared to first generation drug-eluting stents the second generation with thinner stent struts have improved safety and efficacy  Persistence of polymer material on first and second generation drug-eluting stent after completion of drug release has been suggested to be a trigger of a chronic inflammatory response  Third generation coronary drug-eluting stents with biodegradable polymers have been designed to improve safety and efficacy  New ultra-thin strut third generation stents have been developed and may further improve safety and efficacy SORT OUT VII 1Y

Primary Endpoint

Objective:

To compare the efficacy and safety of the thin strut, cobalt-chromium biodegradable polymer sirolimus-eluting Orsiro stent and the stainless steel biodegradable polymer biolimus-eluting Nobori stent in an all-comer population

Primary Endpoint: Target lesion failure

: a composite of cardiac death, myocardial infarction (not related to other than index lesion) or target lesion revascularization within 1 year An event rate of 6.5% was assumed in each group. Sample size of 1.157 patients in each treatment arm, a one-sided 0.050 significance level and a 90% power to detect non-inferiority. Non-inferiority margin of 3.0% Clinically driven event detection based on Danish registries SORT OUT VII 1Y

Patient Population

Inclusion period: November 2012 to February 2014

Criteria of inclusion

  18 years of age or older Chronic stable coronary artery disease or acute coronary syndromes

Criteria of exclusion

     Life expectancy less than one year Allergy to aspirin, clopidogrel, ticagrelor, sirolimus, or biolimus Participation in another randomized trial Unacceptable risk by 12-month dual antiplatelet treatment Unable to provide written informed consent No restrictions were placed on number of treated lesions, treated vessels or lesion length SORT OUT VII 1Y

Patient Characteristics

No. of patients Age (years) Male gender Diabetes Hypertension Current smoker Prior CABG Prior PCI Prior myocardial infarction Body mass Index (kg/m 2 ) Indication for PCI Stable angina pectoris NSTEMI / Unstable angina pectoris STEMI Other

SIROLIMUS-ELUTING ORSIRO STENT

1261 66.1

± 10.7

74.9 % 18.7 % 58.1 % 29.1 % 8.0 % 19.0 % 17.4 % 27.5

± 4.7

44.3 % 30.7 % 21.2 % 3.7 %

BIOLIMUS-ELUTING NOBORI STENT

1264 64.8

± 10.8

75.2 % 18.6 % 56.4 % 32.5 % 7.6 % 20.4 % 17.8 % 27.4

± 4.4

43.9 % 32.6 % 20.7 % 2.8 %

p

<0.01

0.84

0.94

0.39

0.07

0.72

0.39

0.83

0.63

0.47

Lesion Characteristics

No. of lesions No. of lesions per patient Lesion type B2/C Reference vessel size (mm) Left main artery Left anterior descending artery Left circumflex artery Right coronary artery Saphenous vein graft No. of stents

Per patient Per lesion

Total stent length (mm)

Per patient Per lesion

Direct stenting Stent delivery failure

SIROLIMUS-ELUTING ORSIRO STENT

1,590 1.26

56.6

3.2

± 0.6

1.1 % 43.1 % 21.3 % 33.1 % 1.4 % 1.5

± 0.8

1.2

± 0.5

25.2

± 15.5

20.6

± 11.0

14.5 % 1.6 %

BIOLIMUS-ELUTING NOBORI STENT

1,588 1.26

56.2

3.1

± 0.5

0.8 % 42.3 % 22.0 % 33.7 % 1.2 % 1.5

± 0.8

1.2

± 0.5

25.6

± 16.6

20.9

± 11.5

13.7% 2.1 %

p

0.71

0.67

0.02

0.46

0.49

0.45

0.50

0.47

0.56

0.36

1º Endpoint: Target Lesion Failure

(Cardiac death, myocardial infarction index lesion related , target lesion revascularization) Sirolimus-eluting stent 5.2% 4.9% Everolimus-eluting stent

1º Endpoint: Target Lesion Failure

(Cardiac death, myocardial infarction index lesion related , target lesion revascularization) 12 months: ORSIRO 3.8% vs. NOBORI 4.6% P non-inferiority < 0.0001

• Sirolimus-eluting stent 5.2% NOBORI ORSIRO • Everolimus-eluting stent 3.8%

Secondary Endpoints

Rate Ratio 0.89 95% CI 0.46-1.75; p=ns Rate Ratio 0.65 95% CI 0.37-1.13; p=ns 1.4% 1.3% Rate Ratio 0.68 95% CI 0.41-1.12; p=ns Sirolimus-eluting stent 2.9% 5.2% 2.0% 4.9% Everolimus-eluting stent Rate Ratio 0.79 95% CI 0.55-1.13; p=ns 5.2% 4.1% 2.4% 1.6%

Stent Thrombosis

Rate Ratio 0.33 95% CI 0.12-0.92; p=0.03

NOBORI 1.2% ORSIRO 0.4% Rate Ratio 0.55 95% CI 0.26-1.15; p=0.11

Sirolimus-eluting stent 4.9% 1.6% Everolimus-eluting stent ORSIRO 0.9%

Acute coronary syndrom NO Acute coronary syndrom YES Age ≤ 65 years Age > 65 years Diabetes mellitus NO Diabetes mellitus YES LAD NO LAD YES Lesion type C NO Lesion type C YES Male NO Male YES Multi-vessel disease NO Multi-vessel disease YES One stent per patient NO One stent per patient YES Previous MI NO Previous MI YES Previous PCI NO Previous PCI YES STEMI NO STEMI YES All

Target Lesion Failure

In sub-groups

Events (%) SES BES

21 (3.5) 27 (4.1) 15 (2.7) 33 (4.7) 37 (3.6) 11 (4.7) 22 (3.5) 26 (4.2) 26 (5.2) 22 (2.9) 13 (4.1) 35 (3.7) 39 (3.6) 9 (5.1) 25 (3.0) 23 (5.5) 36 (3.5) 12 (5.6) 38 (3.8) 10 (4.2) 31 (3.1) 17 (6.4) 48 (3.8) 29 (4.9) 29 (4.3) 28 (4.3) 30 (4.8) 42 (4.1) 16 (6.8) 32 (4.8) 26 (4.3) 33 (6.7) 25 (3.2) 15 (4.8) 43 (4.5) 52 (4.7) 6 (3.9) 39 (4.6) 19 (4.6) 43 (4.2) 13 (5.9) 42 (4.2) 15 (5.9) 46 (4.6) 12 (4.6) 58 (4.6)

Hazard Ratio 95% CI

0.70 (0.40

– 1.23) 0.96 (0.57

– 1.61) 0.60 (0.32

– 1.13) 0.99 (0.60

– 1.62) 0.88 (0.57

– 1.37) 0.68 (0.32

– 1.46) 0.71 (0.41

– 1.22) 0.97 (0.56

– 1.66) 0.77 (0.46

– 1.29) 0.89 (0.50

– 1.58) 0.86 (0.41

– 1.80) 0.82 (0.52

– 1.28) 0.77 (0.51

– 1.16) 1.32 (0.47

– 3.71) 0.65 (0.39

– 1.07) 1.19 (0.65

– 2.18) 0.84 (0.54

– 1.31) 0.97 (0.44

– 2.12) 0.90 (0.58

– 1.39) 0.71 (0.32

– 1.58) 0.68 (0.43

– 1.07) 1.38 (0.66

– 2.90) 0.83 (0.56

– 1.21)

P

0.43

0.23

0.56

0.43

0.71

0.92

0.34

0.13

0.77

0.61

0.10

Favours SES Favours BES

Conclusion

 The thin strut biodegradable polymer sirolimus-eluting Orsiro stent was non-inferior to the biodegradable polymer biolimus-eluting Nobori stent in unselected patients for the combined safety and efficacy endpoint target lesion failure at 1 year  The sirolimus-eluting Orsiro stent was associated with a reduced risk of definite stent thrombosis SORT OUT VII 1Y

SORT OUT VII 1Y