1. on behalf of the TOTAL Investigators
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 Džavík
on behalf of the TOTAL Investigators

2. Disclosures TOTAL trial was funded by:
Canadian Institutes of Health Research
Canadian Network and Centre for Trials Internationally (CANNeCTIN)
Medtronic Inc.

3. Background: Effect of Thrombectomy at 1 year
Large effect size in TAPAS (2008)
No difference in TASTE (2013)
TAPAS trial (N=1071) showed a large benefit
vs. TASTE (N=7244) showed no benefit of thrombus aspiration
Vlaar PJ, et al. Lancet 2008;371:
Frobert O, et al. N Engl J Med 2013.
Lagerqvist B, et al. N Engl J Med

4. The TOTAL Trial Study Design
STEMI* with Primary PCI ≤12 hours of symptom onset
Sample size of 10,700 for 80% power to detect a 20% Relative Risk Reduction
1:1 Randomization between strategies
Routine Upfront Manual Thrombectomy
followed by PCI
PCI Alone
(only bailout thrombectomy)
Primary Outcome: CV death, MI, cardiogenic shock and class IV heart failure ≤180 days
Safety Outcome: Stroke ≤30 days
Bailout Thrombectomy allowed if PCI alone strategy fails:
Persistent TIMI 0 or 1 flow with large thrombus after balloon pre-dilatation
Persistent large thrombus after stent deployment at target lesion

5. Summary of Primary Results of TOTAL trial
Improvement in Surrogate Outcomes (ST resolution, Distal embolization)
Thrombectomy did not reduce primary outcome at 180 days
Increase in stroke at 30 days
Question:
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:

6. TOTAL Recruitment from 87 sites in 20 countries
Europe
5617
North America
3863
Asia Pacific
865
South America
387
10,732 patients randomized between August 2010 and July 2014

7. TOTAL Trial Flow and Adherence
10,732 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

8. Baseline and Procedural Characteristics
Thrombectomy
N=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%)

9. Primary Outcome (CV death, MI, Shock or CHF) at 1 year

10. Primary Outcome at 1 year
Thrombectomy
(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
( )
0.68
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

11. Safety 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

12. Site Primary PCI Volume: Tertile 1 2450 8.1 8.4 Tertile 2 2139 8.4 7.8
Thrombectomy (%)
PCI Alone (%)
P (INTERACTION)
OVERALL
10064
7.8
7.8
TIMI Thrombus Grade: ≥3
8983
8.0
8.2
<3
1073
6.0
4.9
0.407
TIMI Thrombus Grade: ≥4
7919
8.4
8.5
<4
2137
5.8
5.5
0.759
Symptom Onset:
<6 hrs
8416
7.6
7.4
6-12 hrs
1645
9.3
10.2
0.480
Initial TIMI Flow:
0-1
7453
8.3
8.6
2-3
2517
6.8
5.7
0.195
Site Primary PCI Volume:
Tertile 1
2450
8.1
8.4
Tertile 2
2139
8.4
7.8
Tertile 3
5475
7.5
7.6
0.823
MI Type:
Anterior
4017
9.7
10.1
Non-Anterior
6039
6.7
6.3
0.509
Age:
≤65 yrs
6662
5.5
5.1
>65 yrs
3401
12.6
13.1
0.375
Favours Thrombectomy
Favours PCI Alone
0.5
1.0
2.0

13. Updated Meta-analysis N=20,352 All-Cause Mortality
OR 0.90 (95% CI ) P=0.10

14. Stroke
0.9% thrombectomy vs. 0.6% PCI alone, OR 1.43 (95% CI ) P=0.03

15. Conclusions
Routine 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 stroke
Manual Thrombectomy can no longer be recommended as a routine strategy

16. Available Online at the Lancet

17. Acknowledgements Thank you for Grant Support from and
Executive Committee
S.S. Jolly (co-Principal Investigator)
V. Džavík (co-Principal Investigator)
J.A. Cairns
L. Thabane
S. Yusuf
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
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
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
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
Thank you for Grant Support from and

18. TOTAL Investigators from 87 sites in 20 countries
AUSTRALIA
CANADA
FINLAND
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. Bilodeau
J. Torzewski
N. Vazquez
USA
M.A. dos Santos
R. Leung
GREECE
B. Garcia del Blanco
N. Patel
A. Abizaid
J. Charania
D. Alexopoulos
A. Bethencourt
I.J. Sarembock
CHINA
CZECH REPUBLIC
Ziakas
R. Moreno
J. Blankenship
Y. Xu
P. Hajek
HUNGARY
A. Iniguez Romo
D. Lasorda
J. Qiu
V. Kocka
Ungi
J. Escaned Barbos
M. Sheldon
S. Liu
P. Cervinka
B. Merkely
H. Tizon-Marcos
S. Pancholy
H. Luo
I. Bernat
MACEDONIA
C. Devireddy
D. Horak
S. Kedev
S. Singh

20. Thrombectomy (%) PCI Alone (%) P (INTERACTION) OVERALL 10064 7.8 7.8
Diabetes:
No diabetes
8206
6.8
7.1
Diabetes
1856
12.6
10.9
0.220
GP IIb/IIIa: No
6090
8.1
8.1
Yes
3973
7.4
7.5
0.853
Proximal lesions: No
5330
6.5
6.6
Yes
4734
9.3
9.3
0.902
3 criteria: No
7362
7.3
7.2
Yes*
2702
9.5
9.6
0.855
*proximal or mid LAD culprit lesion and TIMI 0-2 flow
and symptom onset to device <=5 hours
Favours Thrombectomy
Favours PCI Alone
0.5
1.0
2.0