P C R euro

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, Klára Berencsi, Svend Eggert Jensen,

Knud Nørregaard Hansen, Steen Dalby Kristensen, Morten Madsen, Hans Erik Bøtker

Henrik Steen Hansen, Bent Raungaard, Jens Flensted Lassen, Evald Høj Christiansen

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

Potential conflicts of interest

SORT OUT VII 1Y

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

P C R euro

2015

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 SIROLIMUS-ELUTING

ORSIRO STENT

BIOLIMUS-ELUTING

NOBORI STENT p

No. of patients 1261 1264

Age (years) 66.1 ± 10.7 64.8 ± 10.8 <0.01

Male gender 74.9 % 75.2 % 0.84

Diabetes 18.7 % 18.6 % 0.94

Hypertension 58.1 % 56.4 % 0.39

Current smoker 29.1 % 32.5 % 0.07

Prior CABG 8.0 % 7.6 % 0.72

Prior PCI 19.0 % 20.4 % 0.39

Prior myocardial infarction 17.4 % 17.8 % 0.83

Body mass Index (kg/m2) 27.5 ± 4.7 27.4 ± 4.4 0.63

Indication for PCI 0.47

Stable angina pectoris 44.3 % 43.9 %

NSTEMI / Unstable angina pectoris 30.7 % 32.6 %

STEMI 21.2 % 20.7 %

Other 3.7 % 2.8 %

Lesion Characteristics SIROLIMUS-ELUTING

ORSIRO STENT

BIOLIMUS-ELUTING

NOBORI STENT p

No. of lesions 1,590 1,588

No. of lesions per patient 1.26 1.26 0.71

Lesion type B2/C 56.6 56.2 0.67

Reference vessel size (mm) 3.2 ± 0.6 3.1 ± 0.5 0.02

Left main artery 1.1 % 0.8 % 0.46

Left anterior descending artery 43.1 % 42.3 %

Left circumflex artery 21.3 % 22.0 %

Right coronary artery 33.1 % 33.7 %

Saphenous vein graft 1.4 % 1.2 %

No. of stents Per patient 1.5 ± 0.8 1.5 ± 0.8 0.49

Per lesion 1.2 ± 0.5 1.2 ± 0.5 0.45

Total stent length (mm) Per patient 25.2 ± 15.5 25.6 ± 16.6 0.50

Per lesion 20.6 ± 11.0 20.9 ± 11.5 0.47

Direct stenting 14.5 % 13.7% 0.56

Stent delivery failure 1.6 % 2.1 % 0.36

1º Endpoint: Target Lesion Failure (Cardiac death, myocardial infarctionindex lesion related, target lesion revascularization)

Sirolimus-eluting stent

Everolimus-eluting stent

5.2%

4.9%

Sirolimus-eluting stent

Everolimus-eluting stent

5.2%

4.9%

1º Endpoint: Target Lesion Failure (Cardiac death, myocardial infarctionindex lesion related, target lesion revascularization)

12 months: ORSIRO 3.8% vs. NOBORI 4.6% Pnon-inferiority < 0.0001

ORSIRO

NOBORI

3.8%

4.6%

Sirolimus-eluting stent

Everolimus-eluting stent

5.2%

4.9%

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

Rate Ratio 0.68 95% CI 0.41-1.12; p=ns

Rate Ratio 0.79 95% CI 0.55-1.13; p=ns

1.3%

1.4%

1.6%

2.4%

2.0%

2.9%

4.1%

5.2%

Sirolimus-eluting stent

Everolimus-eluting stent

5.2%

4.9%

Stent Thrombosis

ORSIRO

NOBORI

0.9%

1.6%

ORSIRO

NOBORI

0.4%

1.2%

Rate Ratio 0.33 95% CI 0.12-0.92; p=0.03 Rate Ratio 0.55 95% CI 0.26-1.15; p=0.11

Target Lesion Failure

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

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)

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)

0.43

-

0.23

-

0.56

-

0.43

-

0.71

-

0.92

-

0.34

-

0.13

-

0.77

-

0.61

-

0.10

-

-

Events (%) Hazard Ratio

SES BES 95% CI P

Favours SES Favours BES

In sub-groups

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