COMPARE-ABSORB 1 year results

Pieter C. Smits, MD

&

Robert-Jan van Geuns, MD

On behalf of the COMPARE-ABSORB

investigators

Disclosure Statement of Financial Interest

• Grant/Research Support

• Consulting Fees/Honoraria

• Abbott Vascular, St. Jude Medical, Terumo

• Abbott Vascular, St. Jude Medical, Terumo, Astra Zeneca

Within the past 12 months, I or my spouse/partner have had a financial

interest/arrangement or affiliation with the organization(s) listed below.

Affiliation/Financial Relationship Company

All TCT 2018 faculty disclosures are listed online and on the App.

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

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

B. Vaquerizo Monttilla Hospital del Mar,

Barcelona, Spain47

G. Tarantini Azienda Ospedaliera,

Padova, Italie47

V. Kocka University Hospital Kralovs,

Prague, Czech Republic43

P. O’Kane Royal Bournemouth Hospital,

Bournemouth, UK39

P. Buszman American Heart of Poland,

Chrzanow, Poland36

P. Kala University Hospital,

Brno, Czech Republic34

S. Achenbach Universitatsklinikum,

Erlangen, Germany33

M. Maly Central Military Hospital,

Prague, Czech Republic30

K. Milewski American Heart of Poland,

Tychy, Poland30

S. Ijsselmuiden Albert Schweitzer Hospital,

Dordrecht, The Netherlands29

U. Landmesser Charité Campus Benjamin

Berlin, Germany29

C. Naber Elisabethkrankenhaus

Essen, Germany28

P. Tonino Catharina Ziekenhuis,

Eindhoven, The Netherlands26

D. Dudek University Hospital,

Krakow, Poland25

H. Nef Universitatsklinikum

Giessen, Germany25

P. Motreff CHU Clermont-Ferrand

Clermont Ferrand25

J. Sainsous Clinique Rhône Durance,

Avignon, France24

S. Brugaletta Hospital Clinic,

Barcelona, Spain21

C. Liebetrau Kerckhoff Klinik,

Bad Nauheim, Germany19

G. Saad CHR de la Citadelle,

Liege, Belgium19

A. Menozzi Universitaria di Parma

Parma, Italie17

J. Fajadet Clinique Pasteur,

Toulouse, France15

C. Cernetti Ospedale San Giacoma,

Castelfranco Veneto, Italie13

O. Valssecchi Ospedale Papa Giovanni XXIII,

Bergamo, Italie12

M. Meeuwissen Amphia Ziekenhuis,

Breda, The Netherlands11

J. Escaned Hospital Clinico San Carlos,

Madris, Spain11

T. Rudolph Universitatsklinikum,

Koln, Germany11

C. Indolfi Universita Degli Studi Magna Graecia,

Catanzaro, Italie6

B. Loi Azienda Ospeldaliera Brotzu

Cagliari, Italie6

R. Koning Clinique Saint Hilaire,

Rouen, France4

W. Desmet UZ Leuven,

Leuven, Belgium4

J. Mehilli Klinikum der Universitat München,

München, Germany3

P. Lurz Universitatsklinikum,

Leipzig, Germany3

M. Caruso Arnas Civico,

Palermo, Italie3

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

Cu

mu

lativ

e in

cid

en

ce (

%)

0

5

10

15

20

25

Days since initial procedure

0 180 360 540 720 900 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

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

COMPARE-ABSORBInclusion 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

COMPARE-ABSORBExclusion 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

of >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

Key features of COMPARE-ABSORBSpecific 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

Key features of COMPARE-ABSORBPSP 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

REmergent/ Elective PCI

2100 pts

ABSORB

XienceRandomization after successful wiring first target lesion

1Y 5Y

1st analysis: Non-inferiority

in TLF at 1Y

3rd analysis: Cumulative

superiority in TLF at 5Y (or 7Y)

2nd analysis: Superiority in TLF between 1 and 5

years45 sites

across Europe

Original protocol

April 2015

• TLF 1yr in Xience: 8.5% • Non-inferiority margin: 4.5%• Alpha = 0.05• Power=90% • Sample size: 808 x 2 = 1616 pts

• TLF 1-5yr in Xience: 10.5% • TLF 1-5yr in ABSORB 6.3%• Power=90% • Sample size: 1004 x 2 = 2008 pts• Sample size 5% attr. = 2100 pts

Trial design (original)

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

1200

Patients

enrolled

ABSORB II

3 yr results

March

2017

ABSORB III

2 yr results

Study Flow

AIDA

NEJM 2017

FDA warning

letter

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

Start

regulatory

submission

July

2015

Sep.

2015

Oct.

2016

Dec.

2015May

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

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

on ABSORB

1670

Patients

enrolled

Sept.

2018

Study flow

AIDA

NEJM 2017

ABSORB III

2 yr results

FDA warning

letter

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

Base-line characteristics

Risk factorsABSORB

848 patientsXIENCE

822 patientsP 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

L V ejection fraction [%] ± SD 56.4 ± 10.5 56.3 ±10.2 0.83

Base-line characteristics

Indication and treatmentABSORB

848 patients1242 target lesions

XIENCE822 patients

1213 target lesionsP 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

Procedural characteristics

Vessel and lesion treatmentABSORB

1242 target lesions962 procedures

XIENCE1213 target lesions

904 proceduresP 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

Procedural characteristics

Vessel and lesion treatmentABSORB

962 procedures1242 target lesions

XIENCE904 procedures

1213 target lesionsP 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

DAPT usage

97.2 97.6 96.7

80.7

97.8 97.494.5

72.4

0

20

40

60

80

100

120

Discharge 1 month 6 months 12 months

Absorb Xience

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

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%

0-1-2-3- 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

TLF @ 1 yearCardiac death, target vessel myocardial infarction, clinically-indicated target lesion revascularization

5.1%

4.2%

HR 1.24 (0.79 - 1.94)

Plogrank = 0.35

Components of TLFCardiac 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

Stent/Scaffold Thrombosis @ 1 yearDefinite and Probable Stent/Scaffold Thrombosis

(ARC definition)

2.0%

0.6%

HR 3.32 (1.22 - 8.99)

Plogrank=0.01

Clinical events

0.7 0.6

4.0 4.0

7.1

3.6

2.4

6.3

5.1

4.4

0.60.1

2.52.1

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 causedeath

Cardiacdeath

All MI TV MI AnyRevasc

CI-TVR CI-TLR TVF TLF CD or MI

Absorb Xience

p = 0.04

p = 0.82

p = 0.02

% e

ven

t p = 0.35

p = 0.17

p = 0.69

p = 0.92

p = 0.07

p = 0.11

p = 0.79

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. devicethrombosis

Prob. devicethrombosis

Poss. devicethrombosis

Def. or prob.device

thrombosis

Absorb Xience

p = 0.01

p = 0.32 p = 0.58

p = 0.02

0 5 10 15 20

Absorb

Xience

Acute Sub-acute Late

Def. or prob.

device thrombosis

Scaffold thrombosis

• 9 / 16 (56%) of the definite Scaffold

Thrombosis occurred in RVD of ≦ 2.75

by QCA

• 13 /17 (76%) def/prob scaffold

thrombosis occurred within 10 days

post procedure

• Only in 1 case a relationship with DAPT

cessation was observed

Subgroup analyses on TLF

Subgroup analyses on TLF

Conclusions

• In a high risk population for restenosis the

primary endpoint of non-inferiority between

Absorb and Xience for target lesion failure

at 1 year was met

• The target lesion failure rate in this high

risk population was for both devices

impressively good, potentially due to the

applied implantation protocol

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