COMPARE-ABSORB 1 year results Pieter C. Smits, MD & - - PowerPoint PPT Presentation

SLIDE 1

COMPARE-ABSORB 1 year results

Pieter C. Smits, MD & Robert-Jan van Geuns, MD On behalf of the COMPARE-ABSORB investigators

SLIDE 2

Stephan ACHENBACH Emanuele BARBATO Bernard CHEVALIER Javier ESCANED Tommaso GORI Victor KOCKA Guiseppe TARANTINI Robert-Jan VAN GEUNS Peter SMITS Nick WEST Jan TIJSSEN Yoshi ONUMA Marie-Claude MORICE Dariusz DUDEK

Steering Committee

SLIDE 3

Emanuele BARBATO Aalst (66) Bernard CHEVALIER Massy (99) Tommaso GORI Mainz (72) Robert-Jan VAN GEUNS Rotterdam (55) Peter SMITS Rotterdam (201) Nick WEST Cambridge (89) Giovanni ESPOSITO Naples (62) Mohaned EGRED Newcastle (50) Ralph TÖLG Bad Segeberg (67) Mohamed ABDEL-WAHAB Bad Segeberg (67) Adrian WŁODARCZAK Lubin (178)

TOP 10 ENROLLERS

SLIDE 4

• B. Vaquerizo Monttilla

Hospital del Mar, Barcelona, Spain

47

• G. Tarantini

Azienda Ospedaliera, Padova, Italie

47

• V. Kocka

University Hospital Kralovs, Prague, Czech Republic

43

• P. O’Kane

Royal Bournemouth Hospital, Bournemouth, UK

39

• P. Buszman

American Heart of Poland, Chrzanow, Poland

36

• P. Kala

University Hospital, Brno, Czech Republic

34

• S. Achenbach

Universitatsklinikum, Erlangen, Germany

33

• M. Maly

Central Military Hospital, Prague, Czech Republic

30

• K. Milewski

American Heart of Poland, Tychy, Poland

30

• S. Ijsselmuiden

Albert Schweitzer Hospital, Dordrecht, The Netherlands

29

• U. Landmesser

Charité Campus Benjamin Berlin, Germany

29

• C. Naber

Elisabethkrankenhaus Essen, Germany

28

• P. Tonino

Catharina Ziekenhuis, Eindhoven, The Netherlands

26

• D. Dudek

University Hospital, Krakow, Poland

25

• H. Nef

Universitatsklinikum Giessen, Germany

25

• P. Motreff

CHU Clermont-Ferrand Clermont Ferrand

25

• J. Sainsous

Clinique Rhône Durance, Avignon, France

24

• S. Brugaletta

Hospital Clinic, Barcelona, Spain

21

• C. Liebetrau

Kerckhoff Klinik, Bad Nauheim, Germany

19

• G. Saad

CHR de la Citadelle, Liege, Belgium

19

• A. Menozzi

Universitaria di Parma Parma, Italie

17

• J. Fajadet

Clinique Pasteur, Toulouse, France

15

• C. Cernetti

Ospedale San Giacoma, Castelfranco Veneto, Italie

13

• O. Valssecchi

Ospedale Papa Giovanni XXIII, Bergamo, Italie

12

• M. Meeuwissen

Amphia Ziekenhuis, Breda, The Netherlands

11

• J. Escaned

Hospital Clinico San Carlos, Madris, Spain

11

• T. Rudolph

Universitatsklinikum, Koln, Germany

11

• C. Indolfi

Universita Degli Studi Magna Graecia, Catanzaro, Italie

6

• B. Loi

Azienda Ospeldaliera Brotzu Cagliari, Italie

6

• R. Koning

Clinique Saint Hilaire, Rouen, France

4

• W. Desmet

UZ Leuven, Leuven, Belgium

4

• J. Mehilli

Klinikum der Universitat München, München, Germany

3

• P. Lurz

Universitatsklinikum, Leipzig, Germany

3

• M. Caruso

Arnas Civico, Palermo, Italie

3

SLIDE 5

COMPARE-ABSORB trial

Investigator initiated, prospective, single blind, multicenter randomized controlled trial comparing Xience versus Absorb in a high-risk patient and/or complex lesion population

SLIDE 6

Cumulative incidence (%) 5 10 15 20 25 Days since initial procedure 180 360 540 720 900 1080 1260 1440 1620 1800

BES EES

Study background

5 year results COMPARE II 13.7 % 11.8 % TLF

Xience

BP-BES

Vlachojannis et al. JACC Cardiovasc Int 2017;10:1215-21

SLIDE 7

Objectives

• To show non-inferiority between

Absorb and Xience on TLF at 1 year

• Secondary objective is to show

superiority of Absorb on TLF between 1 and 5 years in a landmark analysis

• Tertiary objective is to show

superiority of Absorb on TLF from start to 5 year

SLIDE 8

COMPARE-ABSORB

Inclusion criteria

• Patients with at least one of the following:

i) High-risk characteristics for restenosis Known diabetes and/or multivessel disease of which more than one de-novo target lesion to be treated with the study scaffold/stent ii) Complex de-novo target lesion

• Lesion length >28 mm
• Small vessels: RVD between 2.25-2.75 mm
• Lesion with pre-existing total occlusion
• Bifurcation with single device strategy

SLIDE 9

COMPARE-ABSORB

Exclusion criteria

Patient level

• Patients at age >75 yr
• Renal insufficiency

(GFR <30 ml/min)

• Known LVEF < 30%
• life expectancy < 7 years
• Known non-adherence to

DAPT

• Patients on OAC or NOAC
• Cardiogenic Shock, Killip >2

Lesion / vessel level

• Target lesion reference

vessel diameter < 2.25 and > 4.0 mm

• STEMI with target lesion RVD
• f >3.5mm
• Target lesion with in-

stent/scaffold thrombosis or re-stenosis

• Graft lesions as target

lesions

• Severe tortuosity of target

vessel

• Bifurcation target lesion with

intended 2 device strategy

SLIDE 10

Key features of COMPARE-ABSORB

Specific patient population and implantation technique

• To study a patient population which potentially

might benefit the most by the vascular restoration therapy concept on the long term

• Selection of specific patients and complex

lesions not investigated in previous RCT’s like: STEMI, acute non-STEMI, bifurcations and long lesions and CTO’s

• PSP implantation technique from the start

SLIDE 11

Key features of COMPARE-ABSORB

PSP protocol for ABSORB implantation from the start

• Pre-dilatation mandatory with 1:1 balloon-artery

ratio

• Treatment of target vessels < 2.75 mm QCA,

IVUS or OCT highly recommended

• High pressure (>16 Atm) post-dilatation is

mandatory

• Post-dilatation with NC balloons up to 0.5 mm

larger than the scaffold is recommended

SLIDE 12

R

Em er ergent / Elec ect ive PCI 21 2100 00 pt pt s ABSOR ORB Xience ce Ran andom

• m izat

at ion

• n

aft er er s succes essf sful w iring first t ar arget lesi sion

1Y 1Y 5Y 5Y

1 st

st an

anal alysis: Non

• n-inferiorit y

in TLF at 1Y 3 rd

rd an

anal alysis: Cum ulat i t ive superiorit y t y in TLF at at 5Y ( o ( or 7Y) 2 nd

nd an

anal alysis: Superi riori rit y in T TLF LF bet w t w een 1 a and 5 yea ears

45 sites across Europe Original protocol April 2015

• TLF

LF 1yr r in Xien ence: : 8.5%

• Non
• n-inferiorit y m ar

argin: 4.5%

• Alpha

a = 0.05

• Pow er= 90%

90%

• Sam ple size: 808 x

808 x 2 = 2 = 1616 p 1616 pt s

• TL

TLF 1-5yr in Xien ence: 10. 10.5% 5%

• TL

TLF 1-5y 5yr in ABSORB 6. 6.3% 3%

• Pow er= 90%

90%

• Sam ple size: 1004 x

1004 x 2 = 2 = 2008 p 2008 pt s

• Sam ple s

size 5% at t r t t r. = 2100 p 2100 pt s

Trial design (original)

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Start regulatory submission July 2015 Sep. 2015 Oct. 2016 Dec. 2015 May 2016 Study Start-up period Enrollment period Follow-up period First Patient enrolled 28 Sep 2015 Maassstad Hospital First Initiated site 28 Sep 2015 100 Patients enrolled 600 Patients enrolled All sites enrolling 1200 Patients enrolled Nov. 2016 ABSORB II 3 yr results March 2017 FDA warning letter ABSORB III 2 yr results

Study Flow

SLIDE 14

Protocol revisions

• Lower limit of small vessels was increased

from 2.25 to 2.5 mm

• Secondary long term endpoint was changed to

3 to 7 year landmark analysis

• Prolonged 36 months DAPT regimen in the

scaffold arm was advised

SLIDE 15

R

Em er ergent / Elec ect ive PCI 21 2100 00 pt pt s ABSOR ORB Xience ce Ran andom

• m izat

at ion

• n

aft er er s succes essf sful w iring first t ar arget lesi sion

1Y 1Y 7Y 7Y

1 st

st an

anal alysis: Non

• n-inferiorit y

in TLF at 1Y 3 rd

rd an

anal alysis: Cum ulat i t ive superiorit y t y in TLF at 7Y 7Y ( or 10 10 yr yr) 2 nd

nd an

anal alysis: Superiorit y t y in TLF bet w t w een 3 an and 7 years

45 sites across Europe

• Chan

anged t he secondar ary anal alysis

• Ext e

t ended t h t he follow -up t o t o 7 years

• Excluded t ar

arget vessel ref. diam am . < 2.5 m m m

• Excluded h

high r risk b bleeding pat ient s

• Recom m endat ion o
• n ext e

t ension D DAPT

3Y 3Y

Amended protocol April 2017

Trial design (revised)

SLIDE 16

Start regulatory submission July 2015 Sep. 2015 Oct. 2016 Dec. 2015 May 2016 Study Start-up period Enrollment period Follow-up period First Patient enrolled 28 Sep 2015 Maassstad Hospital First Initiated site 28 Sep 2015 100 Patients enrolled 600 Patients enrolled All sites enrolling 1200 Patients enrolled Nov. 2016 ABSORB II 3 yr results March 2017 31 August DSMB letter Trial put on hold

• Aug. & Sept.

2017 8 September Commercial stop

• n ABSORB

1670 Patients enrolled Sept. 2018

Study flow

AIDA NEJM 2017 ABSORB III 2 yr results FDA warning letter

SLIDE 17

Randomized 1:1 N=1670 (ITT) Xience N=822

1-Year Follow-up

Study Flow and Follow-up

N = 11 no contact N = 11 withdrew consent

96.9% Complete

Xience N=800

97.3% Complete

Absorb N=848 Absorb N=822

N = 13 no contact N = 13 withdrew consent

SLIDE 18

Base-line characteristics

Risk factors ABSORB 848 patients XIENCE 822 patients P value Age [yr] ± SD 61.9 ± 9.4 62.2 ± 9.0 0.61 Male 79.5% (674) 76.3% (627) 0.13 Diabetes mellitus 34.6% (293) 36.1% (296) 0.57 Current smoker 28.8% (241) 26.9% (217) 0.41 Previous smoker 51.9% (289) 50.1% (280) 0.55 Hypercholesterolemia 66.3% (546) 65.8% (531) 0.88 Hypertension 71.6% (601) 69.2% (567) 0.31 Family history of CAD 36.2% (278) 31.7% (241) 0.07 Previous PCI 27.0% (229) 20.2% (238) 0.38 Previous CABG 1.9% (16) 2.6% (21) 0.41 Previous MI 18.2% (154) 20.2% (166) 0.29 Previous stroke 3.4% (29) 4.8% (39) 0.18 Renal insufficiency 3.9% (33) 6.0% (49) 0.054 LV ejection fraction [%] ± SD 56.4 ± 10.5 56.3 ±10.2 0.83

SLIDE 19

Base-line characteristics

Indication and treatment ABSORB 848 patients 1242 target lesions XIENCE 822 patients 1213 target lesions P value Acute coronary syndrome (ACS) 52.1% (442) 48.7% (400) 0.17 STEMI 13.0% (110) 12.5% (103) 0.88 Non-STEMI treatment < 72 hours 13.3% (113) 12.4% (102) 0.57 Multi-vessel treatment 35.7% (303) 37.7% (301) 0.56 Mean target lesions treated ± SD 1.5 ± 0.7 1.5 ± 0.7 0.67 Mean Syntax score ± SD 12.2 ± 7.1 12.2 ± 7.3 0.88 Bifurcation lesions 20.5% (254) 22.2 (269) 0.30 Pre-existing total occlusions 14.6% (181) 13.1% (159) 0.32 Long lesions (>28mm) 25.2% (313) 31.5% (370) <0.001 Small vessel lesions (>2.25 ≤ 2.75 mm) 22.5% (279) 30.5% (370) <0.001

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Procedural characteristics

Vessel and lesion treatment ABSORB 1242 target lesions 962 procedures XIENCE 1213 target lesions 904 procedures P value Pre-dilatation 96.5% (1198) 78.6% (1213) <0.001 Largest balloon (mm ± SD) 3.0 ± 1.0 3.0 ± 0.7 0.96 Non-compliant balloon used 67.9% (814) 52.9% (504) <0.001

• Max. pressure used (Atm.)

15.3 ± 3.5 14.8 ± 3.4 0.002 Cutting / scoring balloon 5.8% (72) 2.3% (28) <0.001 Mean study devices used 1.3 ± 0.7 1.3 ± 0.6 0.07 Post-dilatation 90.7% (1497) 58.3% (906) <0.001 Non-compliant balloon used 93.0% (1392) 85.5% (775) <0.001 Largest balloon diameter (mm ± SD) 3.3 ± 0.4 3.3 ± 0.5 0.97

• Max. pressure largest balloon (Atm)

17.6 ± 3.7 17.5 ± 3.7 0.76

• Max. pressure ≧ 16 Atm

79.7% (1193) 79.5% (720) 0.92 IVUS performed post 14.3% (138) 14.3% (129) 1.0 OCT performed post 9.4% (90) 2.7% (24) <0.001

SLIDE 21

Procedural characteristics

Vessel and lesion treatment ABSORB 962 procedures 1242 target lesions XIENCE 904 procedures 1213 target lesions P value Procedural success 98.4% (947) 98.9% (894) 0.43 Device success 92.4% (1148) 96.8% (1174) <0.001 Successful delivery of device 95.0% (1180) 99.2% (1203) <0.001 Residual stenosis < 30% 96.9% (1203) 97.4% (1182) 0.40

SLIDE 22

DAPT usage

97.2 97.6 96.7 80.7 97.8 97.4 94.5 72.4 20 40 60 80 100 120

Discharge 1 month 6 months 12 months

Absorb Xience

%

P=NS P=0.04 P=NS P<0.001

SLIDE 23

Primary endpoint

1 year TLF non-inferiority analysis

• Assumed difference between Xience and Absorb : 0 %
• Non inferiority margin : 4.5 %
• One sided 2.5% significance level
• TLF rate Xience 4.2%
• TLF rate Absorb 5.1%
• 1
• 2
• 3
• 4

Δ Prim EP %

1 Absorb not inferior Δ Prim. EP: Absorb - Xience = 0.9 % (95% CI: -1.2 – 3.0 %) Absorb is non-inferior compared to Xience P < 0.001

• 5

2 3 4 5

SLIDE 24

TLF @ 1 year

Cardiac death, target vessel myocardial infarction, clinically-indicated target lesion revascularization

5.1% 4.2% HR 1.24 (0.79-1.94) Plogrank = 0.35

SLIDE 25

Components of TLF

Cardiac death Target vessel myocardial infarction Clinically indicated target vessel revascularization

2.4% 2.7% 4.0% 2.1% 0.6% 0.1%

MI definition:

• SCAI (peri-procedural)
• TUD (spontaneous)

HR 4.87 (0.57-41.70) Plogrank = 0.11 HR 0.89 (0.48-1.62) Plogrank = 0.69 HR 1.96 (1.10-3.51) Plogrank = 0.02

SLIDE 26

Stent/Scaffold Thrombosis @ 1 year

Definite Stent/Scaffold Thrombosis (ARC definition)

1.9% 0.6% HR 3.12 (1.14-8.51) Plogrank=0.02

SLIDE 27

Stent/Scaffold Thrombosis @ 1 year

Definite and Probable Stent/Scaffold Thrombosis (ARC definition)

2.0% 0.6% HR 3.32 (1.22-8.99) Plogrank=0.01

SLIDE 28

Clinical events

0.7 0.6 4.0 4.0 7.1 3.6 2.4 6.3 5.1 4.4 0.6 0.1 2.5 2.1 7.4 3.7 2.7 4.8 4.2 2.6 0.0 1.0 2.0 3.0 4.0 5.0 6.0 7.0 8.0 9.0 10.0 All cause death Cardiac death All MI TV MI Any Revasc CI-TVR CI-TLR TVF TLF CD or MI

Absorb Xience

p = 0.04 p = 0.82 p = 0.02

% event

p = 0.35 p = 0.17 p = 0.69 p = 0.92 p = 0.07 p = 0.11 p = 0.79

SLIDE 29

Device thrombosis

1.9 0.1 0.2 2.0 0.6 0.0 0.1 0.6 0.0 1.0 2.0 3.0 4.0 5.0

• Def. device thrombosis
• Prob. device thrombosis
• Poss. device thrombosis
• Def. or prob. device

thrombosis

Absorb Xience

p = 0.01 p = 0.32 p = 0.58 p = 0.02

SLIDE 30

Subgroup analyses on TLF

SLIDE 31

Subgroup analyses on TLF

SLIDE 32

Conclusions

• In a high risk population for restenosis the

primary endpoint of non-inferiority for target lesion failure at 1 year was met between Absorb and Xience

• The target lesion failure rate in a high risk

population was low, potentially due to the applied implantation protocol

SLIDE 33

Conclusions

• Although non-inferiority was met, scaffold

thrombosis and myocardial infarction rate for Absorb was significantly higher compared to Xience, despite applied PSP protocol

• COMPARE-ABSORB will have a 7 year

follow-up to investigate the potential benefit of Absorb in a high risk population