Final Three-Year Outcome of

a Randomized Trial Comparing

Second Generation Drug-eluting Stents Using

Either Biodegradable Polymer or Durable PolymerThe NOBORI Biolimus-Eluting versus XIENCE/PROMUS Everolimus-eluting Stent Trial (NEXT)

Masahiro Natsuaki, MDKyoto University Graduate School of Medicine, Saiseikai Fukuoka General Hospital

Ken Kozuma, MD; Takeshi Morimoto, MD, MPH; Kazushige Kadota, MD;

Toshiya Muramatsu, MD, Yoshihisa Nakagawa, MD, Takashi Akasaka, MD;

Keiichi Igarashi, MD; Kengo Tanabe, MD; Yoshihiro Morino, MD; Tetsuya Ishikawa, MD;

Hideo Nishikawa, MD; Masaki Awata, MD; Masaharu Akao, MD; Hisayuki Okada, MD;

Yoshiki Takatsu, MD; Nobuhiko Ogata, MD; Kazuo Kimura, MD; Kazushi Urasawa, MD;

Yasuhiro Tarutani, MD; Nobuo Shiode, MD; and Takeshi Kimura, MD

On behalf of the NEXT Investigators

Potential conflicts of interest

Speaker's name: Masahiro Natsuaki

I do not have any potential conflict of interest

Study sponsor: Terumo Japan

Background

COMPARE II Cardiac death, myocardial infarction and TVR at 3-year

Smits P. EuroPCR 2014.

The advantage of coronary stent using biodegradable polymer could emerge beyond 1-year after stent implantation, when polymer has been fully degraded.

However, there are only a few randomized controlled trials other than the NEXT reporting the clinical outcomes beyond 1-year after biodegradable polymer biolimus-eluting stent (BP-BES) implantation as compared with durable polymer everolimus-eluting stent (DP-EES) implantation.

Therefore, we report the clinical outcomes of BP-BES compared with DP-EES through 3-year and beyond 1-year after stent implantation in the largest ever reported prospective multicenter randomized open label trial.

Randomization 1:1

3235 patients scheduled for PCI using drug-eluting stentNo Exclusion Criteria (All-comer Design)

NEXT TrialMulticenter, randomized, non-inferiority trial comparing BP-BES with DP-EES

3-Year Clinical Follow-up(N=3158; 97.6%)

DP-EES(N=1582)

<1035 days follow-up: N=36

BP-BES(N=1576)

<1035 days follow-up: N=41

Enrollment from 98 Japanese centers

between May and October, 2011

Nobori BP-BES(N=1617)

Xience/Promus DP-EES(N=1618)

<Primary Endpoint> Efficacy: Target lesion revascularization at 1-yearSafety: Death or Myocardial Infarction at 3-year

<Power Calculation> 3000 patients would yield 91% power to detect non-inferiority

with the non-inferiority margin of 4.3% (True rate 12.2%)

BP-BES (1617) DP-EES (1618) P

Age (years) 69.1 ± 9.8 69.3 ± 9.8 0.49

Male gender 77 % 77 % 0.76Diabetes 46 % 46 % 0.85Hypertension 81 % 82 % 0.81Prior PCI 50 % 51 % 0.9Clinical diagnosis 0.62

Acute myocardial infarction 5.1 % 4.5 %

Unstable angina 12 % 11 %

Stable coronary artery disease 83 % 84 %

Hemodialysis 6.5 % 5.2 % 0.11

Prior myocardial infarction 28 % 28 % 0.81

Prior stroke 10 % 11 % 0.43

Multivessel disease 51 % 51 % 0.9

SYNTAX score 10 (6-17) 10 (6-16) 0.17

No. of lesions treated per patient 1.27 ± 0.56 1.24 ± 0.51 0.1

No. of stents per patient 1.59 ± 0.84 1.6 ± 0.83 0.74

Total stent length per patient (mm) 33.0± 20.3 32.9 ± 20.7 0.87

Stent diameter (mm) 2.88 ± 0.67 2.87 ± 0.64 0.7

Multivessel treatment 13% 11% 0.21

Baseline Characteristics

0% 1.0%-1.0% 2.0% 4.0%

4.3%

BP-BES 9.9% vs. DP-EES 10.3%Pnon-inferiority < 0.0001

Difference: -0.44%Upper one-sided 97.5% CI: 2.2%

Non-inferiority Assessment for the Primary Safety Endpoint

Death or Myocardial Infarction at 3-year

Non-inferiority margin

2.2%

3.0% 5.0%

0%

10%

20%

0 365 730 10950%

10%

20%

0 365 730 1095

Death or Myocardial Infarction

1.0%-1.0% 2.0% 4.0%3.0% 5.0%

Target Lesion Revascularization

Cumulative 3-year Incidence Primary Safety Endpoint Primary Efficacy Endpoint

Cum

ulat

ive

Inci

denc

e (%

)

DP-EES

BP-BES

Log-rank P=0.7

Days after PCI

Interval 0 day 365 days 730 days 1095 days

BP-BES group

N of patients with at least 1 event

89 126 159

N of patients at risk 1617 1524 1478 1416

Cumulative Incidence 5.5% 7.8% 9.9%

DP-EES group

N of patients with at least 1 event

87 124 166

N of patients at risk 1618 1529 1482 1413

Cumulative Incidence 　 5.4% 7.7% 10.3%

DP-EES

BP-BES

Days after PCI

Log-rank P=0.8

Interval 0 day 365 days 730 days 1095 days

BP-BES group

N of patients with at least 1 event

68 99 116

N of patients at risk 1617 1506 1432 1353

Cumulative Incidence 4.3% 6.3% 7.4%

DP-EES group

N of patients with at least 1 event

72 97 112

N of patients at risk 1618 1506 1440 1359

Cumulative Incidence 　 4.5% 6.1% 7.1%

10.3%

7.1%9.9%

7.4%

0%

5%

10%

15%

Clinical Outcomes at 3-Year

6.8%

P = 0.85

7.0%

Death Cardiacdeath

P = 0.57

2.7%2.4%

Stentthrombosis

P = 0.74

0.31% 0.26%

Stroke

3.1% 3.2%

P = 0.93

11.3%

9.9%

P = 0.21

TVRMI

4.0% 3.7%

P = 0.72

BP-BES

DP-EES

Cum

ulati

ve In

cide

nce

730 1095 730 10950%

10%

20%

0

Death or Myocardial Infarction

1.0% 2.0% 4.0%3.0%

Target Lesion RevascularizationPrimary Safety Endpoint Primary Efficacy Endpoint

Cum

ulat

ive

Inci

denc

e (%

)

DP-EES

BP-BES

Landmark Analysis at 1-year

0%

10%

20%

0

Log-rank P=0.88 Log-rank P=0.46

DP-EES

BP-BES

Log-rank P=0.72 Log-rank P=0.39

5.4%

5.2%4.5%

2.7%

5.5%

4.6%

4.3%

3.3%

365 365

Definite Stent Thrombosis

730 10950%

2.5%

5%

0 365

DP-EES

BP-BES

Log-rank P=0.18 Log-rank P=0.32

0.25%0.07%0.06%0.2%

DP-EES: 0.1%/year

BP-BES: 0.04%/year

　Conclusions

　 The safety and efficacy outcomes of BP-BES remained comparable to

those of DP-EES through 3-year and beyond 1-year after stent implantation.

There was no apparent signal suggesting either improvement or

　 impairment of clinical outcomes with BP-BES compared with DP-EES.

Longer-term follow-up is mandatory to fully understand whether BP-BES

could provide any long-term benefit over DP-EES.