total 1 year results of the total trial: randomized trial of manual thrombectomy in stemi ss jolly,...
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TOTAL
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
TOTAL
Disclosures
TOTAL trial was funded by:•Canadian Institutes of Health Research•Canadian Network and Centre for Trials Internationally (CANNeCTIN)•Medtronic Inc.
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Background: 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
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The TOTAL Trial Study Design
PCI Alone(only bailout thrombectomy)
Routine Upfront Manual Thrombectomyfollowed 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:•Persistent 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
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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;372:1389-1398.
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TOTAL Recruitment from 87 sites in 20 countries
North America3863
South America387
Europe5617
Asia Pacific865
10,732 patients randomized between August 2010 and July 2014
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TOTAL 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%)
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5035 Manual Thrombectomy 5029 PCI Alone
5029 included in analysis5035 included in analysis
10,064 underwent PCI for STEMI
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Baseline and Procedural Characteristics
ThrombectomyN=5035
PCI aloneN=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%)
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Primary Outcome (CV death, MI, Shock or CHF) at 1 year
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Primary Outcome at 1 year 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 (0.82 -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
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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 year7 (0.1) 10 (0.2) 0.70 (0.27 – 1.83) 0.46
TOTAL0.5 1.0 2.0
OVERALL 10064
Thrombectomy (%)
7.8
PCI Alone (%)
7.8P (INTERACTION)
TIMI Thrombus Grade:≥3<3
89831073
8.06.0
8.24.9 0.407
TIMI Thrombus Grade:
≥4<4
79192137
8.45.8
8.55.5 0.759
Symptom Onset:
<6 hrs
6-12 hrs
8416
1645
7.6
9.3
7.4
10.2 0.480
Initial TIMI Flow:0-12-3
74532517
8.36.8
8.65.7 0.195
Site Primary PCI Volume:Tertile 1Tertile 2Tertile 3
245021395475
8.18.47.5
8.47.87.6 0.823
MI Type:AnteriorNon-Anterior
40176039
9.76.7
10.16.3 0.509
Age:≤65 yrs>65 yrs
66623401
5.512.6
5.113.1 0.375
Favours Thrombectomy Favours PCI Alone
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Updated Meta-analysis N=20,352All-Cause Mortality
OR 0.90 (95% CI 0.79-1.02) P=0.10
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Stroke
0.9% thrombectomy vs. 0.6% PCI alone, OR 1.43 (95% CI 1.03-1.99) P=0.03
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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
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Available Online at the Lancet
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Acknowledgements
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. Yusuf
Thank you for Grant Support from and
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TOTAL Investigators from 87 sites in 20 countriesAUSTRALIA 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 A. Ziakas R. Moreno J. Blankenship
Y. Xu P. Hajek HUNGARY A. Iniguez Romo D. Lasorda
J. Qiu V. Kocka I. 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
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TOTAL
0.5 1.0 2.0
OVERALL
Diabetes:No diabetesDiabetes
GP IIb/IIIa:NoYes
Proximal lesions:
NoYes
3 criteria:NoYes*
10064
82061856
60903973
53304734
73622702
Thrombectomy (%)
7.8
6.812.6
8.17.4
6.59.3
7.39.5
PCI Alone (%)
7.8
7.110.9
8.17.5
6.69.3
7.29.6
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