Pieter C. Smits, MD Robert-Jan van Geuns, MD On behalf of ...€¦ · 2016 Dec. May 2016 Study...
Transcript of Pieter C. Smits, MD Robert-Jan van Geuns, MD On behalf of ...€¦ · 2016 Dec. May 2016 Study...
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