TCT: EXCELLENT Trial

Seoul National University HospitalCardiovascular Center E CELLENT-RCTSeoul National University HospitalCardiovascular Center

Hyo-Soo Kim MD, PhDon behalf of the investigators

Seoul National University Hospital, Seoul, Korea

Efficacy of Xience/Promus versus Cypherto rEduce Late Loss in stENT

Press Conference

Seoul National University HospitalCardiovascular Center E CELLENT-RCT

Disclosures

I, Hyo-Soo Kim, DO NOT have a financial inter-

est/arrangement or affiliation with one or more

organizations that could be perceived as a real or

apparent conflict of interest in the context of the

subject of this presentation.


Background

Everolimus-Eluting Stent Sirolimus-Eluting Stent

• EES has been shown to be superior to PES with regard to angiographic and clinical endpoints.

• SES has been known to be the most efficacious DES regarding inhibition of neointima and LL

Everolimus is the 40-o-(2-hydroxyethyl) derivative of sirolimus targeting mTOR

• Thinner fluoropolymer (7.8 μm) • EVA:BMA copolymers (13.7 μm)

• Thinner strut thickness (81 μm) • strut thickness (140 μm)

• Cobalt–chromium alloy platform • Stainless steel

Head-to-head comparison of angiographic & clinical outcomes, has not been performed at RCT basis


Objective

EES is non-inferior to SES in

• inhibiting neointimal growth

at 9 months angiography

HypothesisTo evaluate the safety

and long-term efficacy

of Xience/Promus com-

pared with the Cypher

select


Patient EligibilityGeneral Exclusion Criteria

• GI or GU bleeding ≤3 months, major surgery ≤ 2 months• Hb<10 g/dL, PLT<100K• Elective surgical procedure planned ≤ 12 months• LVEF < 25%, or in shock• MI ≤ 72 hours• Creatinine level ≥ 3.0mg/dL or dependence on dialysis• Severe hepatic dysfunction (AST, ALT ≥ x3 UNL)• Patients who have received any stent implantation in the

target vessel prior to enrollment

Angiographic Exclusion Criteria

• Patients with significant LM stenosis• BMS or DES ISR• CTO• True bifurcation lesions requiring two stents

Inclusion Criteria

• > 50% stenosis by visual estimation • Evidence of myocardial ischemia

Stable angina Unstable angina Recent infarction, silent ischemia + functional study or reversible changes

in the ECG c/w ischemia• Target lesion must be located in a native

coronary artery• 2.25mm ≤ RVD ≤ 4.25mm• Lesion length: no limitation• Multiple stenting: no limitation


Study Flow: Angiographic F/U

EESN=1079

Received EES

(1054 Pts, 1388 Lesions)

Received SES

(335 Pts, 414 Lesions)

Did not receive allocated stent: 24 - DES: 17 - BMS: 2 - CABG: 1 - POBA: 1 - Not inserted: 3Failed PCI: 1

Did not receive allocated stent : 29 - DES: 23 - BMS: 0 - CABG: 1 - POBA: 1 - Not inserted: 4Failed PCI: 0

Angiographic F/U (67.3%)

709 Pts, 949 Lesions

Angiographic F/U (64.5%)

216 Pts, 267 Lesions

Enrolled and randomized(N=1443)

Randomized

3:1

SESN=364


Baseline Characteristics Variables ― no. (%) EES

(N=1,079)SES

(N=364) p-value

Age, years ― mean±SD 62.5±10.1 63.4±9.9 0.125

Males 703 (65.2) 228 (62.6) 0.386

Body-mass index, kg/m2 25±3.1 25±2.9 0.885

Diabetes mellitus 402 (37.3) 148 (40.7) 0.248

Chronic renal failure 12 (1.1) 3 (0.8) 0.773

Hypertension 790 (73.2) 266 (73.1) 0.959

Dyslipidemia 820 (76.0) 269 (73.9) 0.422

Current smoker 278 (25.8) 106 (29.1) 0.210

Family history of CAD 99 (9.2) 28 (7.7) 0.388

Previous myocardial infarction 56 (5.2) 17 (4.7) 0.696

Previous percutaneous coronary intervention 99 (9.2) 30 (8.2) 0.589

Previous bypass surgery 12 (1.1) 6 (1.6) 0.419

Previous congestive heart failure 8 (0.7) 1 (0.3) 0.463

Cerebrovascular disease 57 (5.3) 37 (10.2) 0.001

Peripheral vascular disease 13 (1.2) 6 (1.6) 0.594


Lesion and Procedural Characteristics

Variables ― no. (%) EES SES p-value*

No. of stents per lesion 1.21±0.47 1.19±0.42 0.311

No. of stents per patient† 1.64±0.97 1.53±0.87 0.049

Total stent length per lesion ― mm 27.86±13.42 28.55±13.22 0.375

Total stent length per patient† 37.7±24.89 36.85±24.87 0.410

Use of GpIIb/IIIa inhibitors** 19 (1.8) 5 (1.4) 0.617

Minimal luminal diameter (in stent) 2.6±0.46 2.6±0.49 0.848

Minimal luminal diameter (in segment) 2.22±0.51 2.24±0.53 0.554

Diameter stenosis (in stent) 8.59±8.95 8.3±8.3 0.451

Diameter stenosis (in segment) 19.01±11.07 18.37±11.19 0.238

Acute gain (in stent) 1.73±0.54 1.72±0.53 0.753

Acute gain (in segment) 1.35±0.58 1.35±0.57 0.877

Use of intravascular ultrasound (IVUS)* 466 (43.2) 160 (44) 0.798

Lesion success 1444 (99.7) 460 (99.8) 0.817

Device success 1446 (99.9) 457 (99.1) 0.100

Procedure success 1433 (99.0) 457 (99.1) 0.928

*comparisons were performed using the generalized estimating equations (GEE).**compared with the Chi-square test, and †with the independent t-test


QCA Data(1) :all lesions

Variables ― no. (%) EES(N=949)

SES(N=267) p-value*

Follow-up at 9 months Minimal luminal diameter ― mm In stent 2.42±0.53 2.44±0.55 0.458 In segment 2.12±0.52 2.16±0.53 0.256 Diameter stenosis ― % In stent 14.63±13.33 13.94±12.10 0.415 In segment 22.53±13.81 21.02±12.72 0.079 Late luminal loss ― mm In stent 0.19±0.33 0.15±0.33 0.082 In segment 0.10±0.36 0.05±0.34 0.051 Binary restenosis ― % In stent 18 (1.9) 3 (1.1) 0.293 In segment 30 (3.2) 6 (2.3) 0.352 Restenosis pattern** ― % 1.000 Focal 27 (90.0) 6 (100.0) Diffuse 1 (3.3) 0 (0.0) Proliferative 1 (3.3) 0 (0.0) Total occlusion 1 (3.3) 0 (0.0)

*comparisons were performed using the generalized estimating equations (GEE).**compared with the Fishcer’s exact test


EES(N=935)

0.10±0.36 mm

SES(N=266)

0.05±0.34 mm

Mean ΔLL: 0.051 mm

Upper 1-sided 95% CI: 0.091 mm

Non-inferiority p-value

0.023

Prespecified non-inferiority margin: 0.1 mm

Non-inferior

Upper 1-sided 95% CI

-0.01 0.00 0.01 0.02 0.03 0.04 0.05 0.06 0.07 0.08 0.09 0.10 0.11 mm

In-segment late LL

1˚ Endpoint


0.0 1.0 2.0 3.0 4.0

0

20

40

60

80

100

Minimal Luminal Diameter (mm)

% o

f L

esio

ns

Before ProcedureEES

SES

After ProcedureEES

SES

9-month F/UEES

SES

1˚ Endpoint

Minimal Luminal DiametersIn-Sement


EES(N=935)

0.19±0.33 mm

SES(N=266)

0.15±0.33 mm

Mean ΔLL: 0.043 mm

Upper 1-sided 95% CI: 0.082 mm

Non-inferiority p-value

0.007

Prespecified non-inferiority margin: 0.1 mm

Non-inferior

Upper 1-sided 95% CI

-0.01 0.00 0.01 0.02 0.03 0.04 0.05 0.06 0.07 0.08 0.09 0.10 0.11 mm

In-stent late LL

Post-hoc


Minimal Luminal Diameters

0.0 1.0 2.0 3.0 4.0

0

20

40

60

80

100

Minimal Luminal Diameter (mm)

% o

f L

esio

ns

Before ProcedureEES

SES

After ProcedureEES

SES

9-month F/UEES

SES

Post-hoc In-Stent


Months after initial procedure

Cu

mu

lati

ve i

nci

den

ce r

ate

(%)

0 3 6 9 12

0.0

2.0

4.0

1.0

3.0

EES: 1.5%

SES: 1.9%

Log-Rank p-value=0.561

Patient Number at RisksEES 1078 1066 1064 1055 1052

SES 363 356 355 354 354

2˚ Endpoint

Hard Endpoints: Composite of cardiac death, or MI



SES 363 356 355 351 350


Cu

mu

lati

ve i

nci

den

ce r

ate

(%)

0 3 6 9 12

0.0

2.0

4.0

1.0

3.0

5.0

EES: 2.4%

SES: 1.7%


2˚ Endpoint

Soft Endpoints TLR


: Composite of cardiac death, MI, or ID-TLR


SES 363 356 355 351 350


Cu

mu

lati

ve i

nci

den

ce r

ate

(%)

0 3 6 9 12

0.0

2.0

4.0

1.0

3.0

5.0

EES: 3.7%

SES: 3.0%


2˚ Endpoint

Target Lesion Failure


: Definite/Probable ST by ARC definition


SES 363 361 360 356 355


Cu

mu

lati

ve i

nci

den

ce r

ate

(%)

0 3 6 9 12

0.0

0.4

0.8

0.2

0.6

1.0

EES: 0.4%

SES: 0.8%


2˚ Endpoint

Stent Thrombosis


Summary : EXCELLENT-RCT• The efficacy of EES was non-inferior to SES in inhibiting late

loss at 9 months & clinical events at 12 months.

• The incidence of ST was not different between EES and SES al-though numerically lower in EES.

• Tendency of higher late-loss in EES than SES may lead to the in-triguing reciprocal trend between soft versus hard endpoints : higher incidence of TLR but lower incidence of death, MI, or ST.

should be confirmed in the larger study in the future

• Long term follow up will tell us whether Xience/Promus will offer similar efficacy along with better long term safety compared with the best 1st generation DES, Cypher.


0.70000000000000

11.1

All-Cause Death (%)

p=0.485

EESN=1,057

SESN=359

0.3

0.60000000000000

1

Cardiac Death (%)

p=0.606

EESN=1,057

SESN=359

1.3 1.4

Myocardial Infarc-tion(%)

p=1.000

EESN=1,057

SESN=359

2˚ Endpoint

Clinical Outcomes at 1 Year


2.5

1.7

ID-TLR(%)

p=0.385

EESN=1,057

SESN=359

3.1

2.2

ID-TVR (%)

p=0.383

EESN=1,057

SESN=359

2˚ Endpoint

Clinical Outcomes at 1 Year


3.8

3.1

TLF (%)(C-death, MI, ID-TLR)

p=0.527

EESN=1,057

SESN=359

4.5

3.6

TVF (%)(C-death, MI, TVR)

p=0.503

EESN=1,057

SESN=359

2.0 2.5

Death or MI (%)

p=0.554

EESN=1,057

SESN=359

2˚ Endpoint

Composite Endpoints


0.3

0.8

Definite ST (%)

p=0.175

EESN=1,057

SESN=359

0.4

0.8

Definite/Probable ST

p=0.379

EESN=1,057

SESN=359

2˚ Endpoint

ARC Stent Thrombosis


Subgroups Pt No. Relative Risk (95% CI) Int P

DM Yes (N=542)0.423

No (N=874)Age ≥ 70 (N=371)

0.952< 70 (N=1045)

Lesion length (mm) > 20 (N=622)0.552

≤ 20 (N=794)CCR (mg/dL) ≥ 60 (N=243)

0.699< 60 (N=1173)

Multivessel ds Yes (N=735)0.985

No (N=681)ACS Yes (N=728)

0.049No (N=688)

Overall (N=1416) 0.527

0.25 0.5 1 2 4 8

Favors EES Favors SES

2˚ Endpoint

: Composite of cardiac death, MI, or ID-TLR

Target Lesion Failure


In-segment & in-stent LL in long lesion or DM subgroup

Variables EES SES Total Mean ΔLL(EES-SES)

Upper 1-sided95% CI p-value

1˚Endpoint: In-segment LLL

Total 935 266 1,201 0.0507 0.0912 0.023

Long lesion (≥ 20mm) 369 111 480 0.0344 0.0962 0.041

DM 359 109 468 0.1105 0.1746 0.620

Post-hoc: in-stent LLL

Total 935 266 1,201 0.0431 0.0811 0.007

Long lesion (≥ 20mm) 369 111 480 0.0328 0.0920 0.031

DM 359 109 468 0.1230 0.1824 0.765


Baseline Characteristics Variables ― no. (%) EES

(N=1,079)SES

(N=364) p-value

Multivessel disease 564 (52.3) 185 (50.8) 0.633

Left ventricular ejection fraction, % 61.4±9.4 60.8±9.8 0.335

Clinical indication 0.115

Silent ischemia 39 (3.6) 16 (4.4)

Chronic stable angina 472 (43.7) 172 (47.3)

Unstable angina 464 (43.0) 139 (38.2)

NSTEMI 76 (7.0) 20 (5.5)

STEMI 28 (2.6) 17 (4.7)

Medications at discharge

Aspirin 1,066 (99.3) 356 (98.9) 0.510

Clopidogrel 1,063 (99.0) 357 (99.2) 1.000

Statin 892 (83.1) 304 (84.4) 0.539

ACE inhibitor 355 (33.1) 119 (33.1) 1.000

Angiotensin II-receptor antagonist 356 (33.1) 122 (33.9) 0.796

Beta-blocker 665 (61.9) 214 (59.4) 0.404

Calcium-channel blocker 362 (33.7) 128 (35.6) 0.522


QCA Data(1) :all lesions

Variables ― no. (%) EES(N=949)

SES(N=267) p-value*

Before procedure

Lesion length ― mm 20.34±11.80 20.89±11.44 0.512

Reference vessel diameter ― mm 2.86±0.49 2.86±0.52 0.937

Minimal luminal diameter― mm 0.87±0.47 0.83±0.47 0.278

Diameter stenosis ― % 69.57±15.14 71.02±14.83 0.178

Immediately after procedure

Minimal luminal diameter ― mm

In stent 2.60±0.45 2.59±0.48 0.796

In segment 2.22±0.51 2.21±0.52 0.968

Diameter stenosis ― %

In stent 8.57±8.94 8.30±8.63 0.577

In segment 19.13±11.30 18.42±10.82 0.322

Acute gain ― mm

In stent 1.73±0.54 1.76±0.54 0.526

In segment 1.35±0.57 1.38±0.56 0.364

*comparisons were performed using the generalized estimating equations (GEE).

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