Randomized trial of manual Thrombectomy in STEMI SS Jolly JA Cairns S Yusuf MJ Rokoss P Gao B Meeks S Kedev G Stankovic R Moreno A Gershlick S Chowdhary ID: 807202
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Slide1
1 year results of the TOTAL trial: Randomized trial of manual Thrombectomy in STEMI
SS Jolly, JA Cairns, S Yusuf, MJ Rokoss, P Gao, B Meeks, S Kedev, G Stankovic, R Moreno, A Gershlick, S Chowdhary, S Lavi, K Niemelä, I Bernat, WJ Cantor, AN Cheema, PG Steg, RC Welsh, T Sheth, OF Bertrand, A Avezum, R Bhindi, MK Natarajan, D Horak, RCM Leung, S Kassam, SV Rao, M El-Omar, SR Mehta, JL Velianou, S Pancholy, V Džavíkon behalf of the TOTAL Investigators
Slide2DisclosuresTOTAL trial was funded by:
Canadian Institutes of Health ResearchCanadian Network and Centre for Trials Internationally (CANNeCTIN)Medtronic Inc.
Slide3Background: Effect of Thrombectomy at 1 year
Large effect size in TAPAS (2008)No difference in TASTE (2013)Vlaar PJ, et al. Lancet 2008;371:1915-20.Frobert O, et al. N Engl J Med 2013.Lagerqvist B, et al. N Engl J Med. 2014.TAPAS trial (N=1071) showed a large benefit
vs
. TASTE (
N=7244) showed
no benefit of thrombus aspiration
Slide4The TOTAL Trial Study Design
PCI Alone(only bailout thrombectomy)
Routine
Upfront Manual Thrombectomy
followed by PCI
Primary Outcome: CV death,
MI
,
cardiogenic shock
and class IV heart failure ≤180 days
Safety Outcome:
Stroke
≤30 days
1:1 Randomization between strategies
Bailout
Thrombectomy
allowed if PCI alone strategy fails:
P
ersistent TIMI 0 or 1 flow with large thrombus after balloon pre-dilatation
Persistent large thrombus after stent deployment at target lesion
STEMI* with Primary PCI ≤12
hours of
symptom onsetSample size of 10,700 for 80% power to detect a 20% Relative Risk Reduction
Slide5Summary of Primary Results of TOTAL trialImprovement in Surrogate Outcomes (ST resolution, Distal embolization)Thrombectomy did not reduce primary outcome at 180 days
Increase in stroke at 30 daysQuestion:Would the benefit for surrogate outcomes translate into a long term benefit at 1 year?Jolly SS, et al. N Engl J Med. 2015;372:1389-1398.
Slide6TOTAL Recruitment from 87 sites in 20 countries
North America3863South America387Europe5617Asia Pacific86510,732 patients randomized between August 2010 and July 2014
Slide7TOTAL
Trial Flow and Adherence10,732 enrolled and randomized Cross-over to Thrombectomy as initial strategy in 70 (1.4%)Bailout Thrombectomy in 354 (7%)
Crossover to PCI alone
in 231 (4.6%)
TOTAL
5035 Manual
Thrombectomy
5029 PCI Alone
5029 included in analysis
5035 included in analysis
10,064 underwent PCI for STEMI
Slide8Baseline and Procedural Characteristics
ThrombectomyN=5035
PCI alone
N=5029
Mean Age
61.1 years
60.9 years
Killip
Class ≥2
4.4%
4.2%
Anterior MI
39.0%
40.9%
Pre PCI TIMI 0-1 flow
3705 (73.6%)
3748 (74.5%)
TIMI Thrombus Grade ≥3
4529 (90%)
4454 (88.6%)
Upfront GP
IIb
IIIa
inhbitor
1143 (22.7%)
1276 (25.4%)
Drug eluting stent
2250 (44.7%)
2266 (45.1%)
Slide9Primary Outcome (CV death, MI, Shock or CHF) at 1 year
Slide10Primary Outcome at 1 year
1 yearThrombectomy (N=5033) (%)PCI alone
(N=5030)
(%)
HR
95% CI
p
CV
death, MI,
shock
or
class
IV heart failure
395 (7.8)
394
(7.8)
1.00
(0.87
– 1.15)
0.99
CV
death
179 (3.6)
192 (3.8)
0.93
(0.76 – 1.14)
0.48
Recurrent
MI
125 (2.5)
118 (2.3)
1.05
(0.82 -1.36)
0.68
Cardiogenic
Shock
95 (1.9)
105 (2.1)
0.90
(0.68
– 1.19)
0.47
Class
IV heart failure
106 (2.1)
96 (1.9)
1.01
(0.83 – 1.45)
0.50
Slide11Safety Outcomes at 1 year
Thrombectomy (N=5033) (%)PCI alone (N=5030) (%)
HR
95% CI
p
Stroke at
1 year
60 (1.2)
36 (0.7)
1.66
(1.10
– 2.51)
0.015
Stroke or TIA at
1 year
73 (1.4)
44 (0.9)
1.65
(1.14 – 2.40)
0.008
Landmark Analyses
Stroke 180
days to 1 year
7 (0.1)
10 (0.2)
0.70
(0.27 – 1.83)
0.46
Slide120.5
1.0
2.0
OVERALL
10064
Thrombectomy (%)
7.8
PCI Alone (%)
7.8
P (INTERACTION)
TIMI Thrombus Grade:
≥
3
<3
8983
1073
8.0
6.0
8.2
4.9
0.407
TIMI Thrombus Grade:
≥
4
<4
7919
2137
8.4
5.8
8.5
5.5
0.759
Symptom Onset:
<6
hrs
6-12 hrs
8416
1645
7.6
9.3
7.4
10.2
0.480
Initial TIMI Flow:
0-1
2-3
7453
2517
8.3
6.8
8.6
5.7
0.195
Site Primary PCI Volume:
Tertile
1
Tertile 2
Tertile 3
2450
2139
5475
8.1
8.4
7.5
8.4
7.8
7.6
0.823
MI Type:
Anterior
Non-Anterior
4017
6039
9.7
6.7
10.1
6.3
0.509
Age:
≤
65
yrs
>65 yrs
6662
3401
5.5
12.6
5.1
13.1
0.375
Favours Thrombectomy
Favours
PCI Alone
Slide13Updated Meta-analysis N=20,352All-Cause Mortality
OR 0.90 (95% CI 0.79-1.02) P=0.10
Slide14Stroke
0.9% thrombectomy vs. 0.6% PCI alone, OR 1.43 (95% CI 1.03-1.99) P=0.03
Slide15ConclusionsRoutine thrombectomy compared to PCI alone did not reduce CV death, MI, shock or heart failure at 1 year
Routine thrombectomy was associated with increased rate of strokeManual Thrombectomy can no longer be recommended as a routine strategy
Slide16Available Online at the Lancet
Slide17Acknowledgements
Steering Committee
A.
Avezum
M.K. Natarajan
I.
Bernat
K.
Niemelä
O. Bertrand
S.
Pancholy
R.
Bhindi
S.V. Rao
W.J. Cantor
M.
Rokoss
B. Meeks
G.
Stankovic
A.
Gershlick
P.G.
Steg
S.
Kedev
J.M. ten Berg
R. Moreno
R.C. Welsh
C.K.
Naber
P.
Widimsky
Y.
Xu
Data Monitoring Committee
G. Wyse (Chair)
J.P.
Bassand
D. Bhatt
M.
LeMay
G. Wells
J. Pogue (DMC statistician)
Angiographic Core Lab
C. Overgaard, V. Sharma, W. Chan,
F. Fuchs, J.
Chiha
, T.
Hamid,
S. Bui, M.
Sibbald
, V.
Džavík
ECG Core Lab
M. Eskola, K. Nikus, J. Koivumäki,
K. Niemelä
PHRI Project Office
Study Team
B. Meeks (Program Manager)
S. Ahmad (Research Coordinator)
M. Lawrence
L. Floyd
M. McClelland
M. Wild
S. Batey
A. Fatima
Statisticians
J. Pogue
O. Shestakovska
P. Gao
Adjudication Committee
M.
Rokoss
(Chair), A.
Avezum
, K.
Bainey
,
P.
Domsik
, G.
Ducrocq
, M.
Eskola
,
G. Fodor, P.
Hajek
, B. Hart, P.
Kanjana
,
J.
Karasconyi
, K.
Kervinen
, T. Lai,
D.
Mancevski
, L. Morillo, A.
Neskovic
,
K. Ng, K.
Niemelä
, W.
Oczkowski
,
G. Oliveira, M. Pan, P.
Paulu
, D.
Petrovska-Cvetskovska
, I. Plaza, H.
Romppanen
,
J.D.
Schwalm
, A.
Shoamanesh
, T.
Sotirov
, D. Topic, N.
Valettas
, K.
Vondrak
,
P.
Widimský
, V.
Zenios
Quality Assurance Committee
C. Ainsworth, D. Al
Khdair
, A.
Alazzoni
,
N. Ali, A. Al-Saleh, A.
Avezum
, F.
Botto
,
W. Chan, J. Cohen, M.
Eskola
, F. Fuchs,
A.
Gangasandra
Basavaraj
, P.
Hajek
,
V. Hsieh, K. Jolly, K.
Kervinen
,
J.
Manolakos
, M. Natarajan, G. Oliveira,
J.
Paikin, S. Pandie, P. Paulu, S. Pizzale
, M. Rokoss, J.D. Schwalm, K. Shufelt, T.
Sotirov, D. Topic, M. Tsang, N. Valettas, K. Vondrak, D. Wright
Executive Committee
S.S. Jolly (co-Principal Investigator)
V.
Džavík
(co-Principal Investigator)
J.A. Cairns
L. Thabane
S. YusufThank you for Grant Support from and
Slide18TOTAL Investigators from 87 sites in 20 countries
AUSTRALIACANADAFINLAND
NETHERLANDS
UNITED
KINGDOM
A. Rahman
S. Jolly
K.
Niemelä
J.M
. ten
Berg
A.
Gershlick
R.
Bhindi
A. Fung
H.
Romppanen
NEW
ZEALAND
S.
Chowdhary
J. Weaver
A. Cheema
FRANCE
G. Devlin
A. Jain
AUSTRIA
O. Bertrand
G.
Sideris
SERBIA
N.
Curzen
I. Lang
V.
Džavík
P.G
.
Steg
G.
Stankovic
M. El-Omar
BELGIUM
S.
Kassam
N.
Delarche
SOUTH KOREA
M.
Seddon
S.
Pourbaix
A. Della
Siega
F.
Schiele
W. Kim
J. Shannon
BRAZIL
T.
Cieza
S.
Marliere
S. Jin Lee
R. Oliver
M. Andre
Tebet
S.
Lavi
GERMANY
M-H.
Jeong
J. Gunn
A.
Kormann
N.
Nadeem
N. Werner
S-H. Kim
S. Hetherington
A.
Zago
R. Welsh
C.
Naber
SPAIN
K. Grosser
P.
Caramori
W. Cantor
M. Greif
J.
Mauri
J. Glover
V. Lima
L. BilodeauJ. TorzewskiN. Vazquez
USAM.A. dos SantosR. Leung
GREECE
B. Garcia del
Blanco
N. Patel
A. AbizaidJ. CharaniaD. Alexopoulos
A. BethencourtI.J. SarembockCHINA
CZECH REPUBLICZiakasR. Moreno
J. BlankenshipY. XuP. Hajek
HUNGARYA. Iniguez RomoD. Lasorda
J. QiuV. KockaUngi
J. Escaned BarbosM. SheldonS. Liu
P. CervinkaB. MerkelyH. Tizon-Marcos
S. PancholyH. LuoI. Bernat
MACEDONIAC. Devireddy
D.
Horak
S.
Kedev
S. Singh
Slide19Slide200.5
1.0
2.0
OVERALL
Diabetes:
No diabetes
Diabetes
GP
IIb
/
IIIa
:
No
Yes
Proximal lesions:
No
Yes
3 criteria:
No
Yes*
10064
8206
1856
6090
3973
5330
4734
7362
2702
Thrombectomy (%)
7.8
6.8
12.6
8.1
7.4
6.5
9.3
7.3
9.5
PCI Alone (%)
7.8
7.1
10.9
8.1
7.5
6.6
9.3
7.2
9.6
P (INTERACTION)
0.220
0.853
0.902
0.855
Favours Thrombectomy
Favours PCI Alone
*proximal or mid LAD culprit lesion and TIMI 0-2 flow
and symptom onset to device <=5 hours