J BERLAND

Clinique Saint Hilaire

ROUEN

DUREE de la BITHERAPIE

dans les ETUDES LEADERS

LEADERS ‘all-comers’ Trial Design

1o endpoint: MACE: Cardiac death, MI, clinically-indicated TVR (9 mo)

2o endpoints: Death, CV death, MI, TLR, TVR

Stent thrombosis according to ARC

Angiographic study: In-stent % diameter stenosis (9 mo)

Late loss, binary restenosis

DAPT recommended for 12 months

BioMatrix Flex™ (BES)*

N=850

Cypher® Select™ (SES)

N=850

Stable and ACS Patients Undergoing PCI

N=1700 Patients

10 European centers

1:3 Randomisation

Clinical F/U

N=640

Angio F/U

N=210

Clinical F/U

N=640

Angio F/U

N=210

Assessor-blind

1:1 Randomisation

Antiplatelet Agent Utilization

BES SES P value*

Aspirin

At 1 year 786/810 (97%) 770/801 (96%) 0.32

At 2 years 749/789 (95%) 733/777 (94%) 0.60

At 3 years 714/757 (94%) 709/748 (95%) 0.69

At 4 years 694/745 (93%) 681/730 (93%) 0.93

Clopidrogel or ticlopidine

At 1 year 552/810 (68%) 534/801 (67%) 0.53

At 2 years 185/789 (23%) 189/774 (24%) 0.68

At 3 years 148/757 (20%) 153/749 (20%) 0.67

At 4 years 119/745 (16%) 135/730 (18%) 0.21

Dual antiplatelet therapy

At 1 year 536/810 (66%) 513/801 (64%) 0.37

At 2 years 171/789 (22%) 168/777 (22%) 0.98

At 3 years 126/757 (17%) 133/749 (18%) 0.57

At 4 years 96/745 (13%) 111/730 (15%) 0.21

* P values for superiority

Ischinger et al., oral presentation, TCT 2011

Definite Stent Thrombosis (ARC)

0

1

2

3

4

5

6

0 6 12 18 24 30 36 42 48

%

Months

BES SES

2% 2.2% 2.2%

2.4%

2% 2.5%

2.9%

4%

Δ 0.3 Δ 0.7

Δ 1.6

3-year RR

0.78 (0.43 -1.432)

P=0.43*

2-year RR

0.90 (0.483 -1.67)

P=0.73*

4-year RR

0.62 (0.35 -1.08)

P=0.09*

1-year RR

0.99 (0.51-1.95)

P=0.98*

Number

s at risk

SES 850 817 801 787 776 759 750 730 714

BES 857 821 804 792 787 780 774 757 746

* P values for superiority

Stefanini G. et al., The Lancet, 2011

Ischinger et al., oral presentation, TCT 2011

0

1

2

3

4

5

6

%

0 6 12 18 24 30 36 42 48

Months after index PCI

0 to 1 year RR

0.99 (0.51-1.95)

P=0.98*

1 to 4 year RR

0.20 (0.06-0.67)

P=0.004*

BES

SES

857 821 804 792 787 780 774 757 746 BES

850 817 801 787 776 759 750 730 714 SES

No. at risk

2.0%

0.4%

2.0%

2.0%

P for interaction=0.017 * P values for superiority

Stefanini G. et al., The Lancet, 2011

Ischinger et al., oral presentation, TCT 2011

Definite ST

Landmark Analysis @ 1 Year

7

10857-0

00-E

N –

Rev.0

1

Effect of DAPT Discontinuation

2,2

0 0

2,9

2,4

0,4

0,0

0,5

1,0

1,5

2,0

2,5

3,0

3 Y ST in LEADERSST after DAPT d/c <12 M

ST after DAPT d/c >12 M

BES SES

%

N=0/165 N=4/169 N=2/515 N=0/540

Overall Population Patient who d/c DAPT

P = 0.12*

P = 0.24*

*P values for superiority (Fisher Exact Test)

3,5

38,3

0

10

20

30

40

50

60

BES SES

-33.1

(-61.7 to –10.3)

P<0.01

LEADERS - OCT Substudy @ 9 Months

Lesions With At Least

5% Uncovered Struts

(%)

29 Lesions 35 Lesions

BES

29 Lesions

SES

35 Lesions

Barlis P et al. Eur Heart J 2010, 31(2):165-176

RECOMMENDATIONS

EUROPEENNES 2010

ARGUMENTAIRE CONTRE UNE MAUVAISE

IDEE TOUTE FAITE: PROLONGER LE

PLAVIX SYSTEMATIQUEMENT

CLOPIDOGREL après implantation

de STENT ACTIF:

L’OPTION COURTE

J BERLAND

SAINT HILAIRE ROUEN

AHA

ACC ESC

SFC

HIGH TECH 2009

Trial Also comparing

stents

Devices DAPT duration (months)

Thrombotic events

Bleeding events

Status

DES LATE (n=2’701)

No SES, PES, ZES

12 vs. 24 No difference (card.death, MI)

No difference (TIMI maj.)

Published (NEJM 2010)

PRODIGY (n=2’013)

No BMS(25%), ZES, PES, EES

6 vs. 24 No difference (death,MI,CVA)

6 mth better (BARC)

Published (Circulation 2012)

RESET (n=2’117) Yes E-ZES vs. SES, EES, ZES

3 (E-ZES) vs.12

(other DES)

No difference (death,MI,ST)

No difference Published (JACC 2012)

EXCELLENT (n=1’443)

Yes EES & SES 6 vs. 12 No difference (TVF)

No difference (TIMI maj.)

Published (Circulation 2012)

DAPT (n=20’000)

No DES (15’000) BMS (5’000)

12 vs. 30 NYK NYK Ongoing

OPTIMIZE (n=3’120)

No E-ZES 3 vs. 12 NYK NYK Ongoing

ZEUS (n=1’600)

Yes ZES vs. BMS 1 (stable) 6+ (ACS)

NYK NYK Ongoing

ISAR-SAFE (n= 6’000)

No DES

6 vs. 12 NYK NYK Ongoing

ISAR TRIPLE (n= 600)

No DES 1.5 vs. 6 (all on AVK)

NYK NYK Ongoing

ETUDES RANDOMISEES SUR LA DUREE DE LA DOUBLE AAP après STENT ACTIF

Trial Also comparing stents

Devices DAPT duration (months)

Thrombotic events Bleeding events

Status

DES LATE (n=2’701) No SES, PES, ZES

12 vs. 24 No difference (card.death, MI)

No difference (TIMI maj.)

Published (NEJM 2010)

PRODIGY (n=2’013) No BMS(25%), ZES, PES, EES

6 vs. 24 No difference (death,MI,CVA)

6 mth better (BARC)

Published (Circulation 2012)

RESET (n=2’117) Yes E-ZES vs. SES, EES, ZES

3 (E-ZES) vs.12

(other DES)

No difference (death,MI,ST)

No difference Presented (ACC 2012)

EXCELLENT (n=1’443)

Yes EES & SES 6 vs. 12 No difference (TVF)

No difference (TIMI maj.)

Published (Circulation 2012)

DAPT (n=20’000)

No DES (15’000) BMS (5’000)

12 vs. 30 NYK NYK Ongoing

OPTIMIZE (n=3’120)

No E-ZES 3 vs. 12 NYK NYK Ongoing

ZEUS (n=1’600)

Yes ZES vs. BMS 1 (stable) 6+ (ACS)

NYK NYK Ongoing

ISAR-SAFE (n= 6’000)

No DES

6 vs. 12 NYK NYK Ongoing

ISAR TRIPLE (n= 600)

No DES 1.5 vs. 6 (all on AVK)

NYK NYK Ongoing

ETUDES RANDOMISEES SUR LA DUREE DE LA DOUBLE AAP après STENT ACTIF

XIENCE V USA: THROMBOSE DE STENT entre 30 j et 1AN

Après interruption de la double anti-agrégation

ETUDES CLINIQUES DU XIENCE pour le marquage CE

INERRUPTION DES ANTI-AGREGANTS à 3 MOIS

THROMBOSES DE STENT et INTERRUPTION DES AAP

ETUDES sur LE XIENCE

RECOMMENDATIONS EUROPEENNES 2010

Birth of a concept (May 2011)

A forgotten patient population

A new polymer-free metallic stent

Current DAPT trend :

« shorter is better »

Urban, oral presenation, EuroPCR 2012

Age ≥ 75 years

Oral anticoagulants needed after PCI

Planned major surgery (within next year)

Baseline Hb <11 g/dl or TF during prior 4 weeks

Hospital admission for bleeding during past year

Any prior intra-cerebral bleed

Any stroke during the past year

Cancer diagnosed or treated < 3 years

Main inclusion criteria

Urban, oral presenation, EuroPCR 2012

Age ≥ 75 years

Oral anticoagulants needed after PCI

Planned major surgery (within next year)

Baseline Hb <11 g/dl or TF during prior 4 weeks

Hospital admission for bleeding during past year

Any prior intra-cerebral bleed

Any stroke during the past year

Cancer diagnosed or treated < 3 years

Main inclusion criteria

Urban, oral presenation, EuroPCR 2012

Trial design

• Biosensors BioFreedom™ BA9 Drug-Coated Coronary Stent (DCS).

• Biosensors Gazelle™ Bare Metal Coronary Stent (BMS)

Two stents

• ASA 100-160 mg OD, indefinitely

• Clopidogrel 75 mg OD (or another P2Y12 inhibitor) for one month only

One DAPT regimen

Urban, oral presenation, EuroPCR 2012

Clinical Follow-Up

Primary safety endpoint: Composite of cardiac death, MI, definite/probable stent thrombosis at 1 year

(Non-inferiority)

Primary efficacy endpoint: Clinically driven TLR at 1 year

(Superiority)

DAPT mandated for 1 month only, followed by long term SAPT

BioFreedom™

DCS

Gazelle™

BMS

Prospective, multi-center, multi-national, double blinded randomized trial

High Bleeding Risk PCI population

(ACS + Elective stable patients)

LEADERS FREE Trial Design

1:1 randomization

1 mo 2 mo 4 mo 1 yr 2 yr

2500 patients in 60 centers worldwide

PI: Philip Urban

RECOMMENDATIONS

EUROPEENNES 2015

Durée de la double Antiagrégation

Plaquettaire après STENT ACTIF

3 mois pour les patients standards avec stents

actifs de seconde génération. I C

1 mois pour les patients à haut risque hémorragique

Avec le stent BIOFREEDOM I A