1 year results of the TOTAL trial: - PowerPoint Presentation

Presentation on theme: "1 year results of the TOTAL trial:"— Presentation transcript

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

DisclosuresTOTAL trial was funded by:

Canadian Institutes of Health ResearchCanadian Network and Centre for Trials Internationally (CANNeCTIN)Medtronic Inc.

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

The 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

Summary 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.

TOTAL Recruitment from 87 sites in 20 countries

North America3863South America387Europe5617Asia Pacific86510,732 patients randomized between August 2010 and July 2014

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%)

TOTAL

5035 Manual

Thrombectomy

5029 PCI Alone

5029 included in analysis

5035 included in analysis

10,064 underwent PCI for STEMI

Baseline 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%)

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

Primary 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

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

0.5

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

Updated Meta-analysis N=20,352All-Cause Mortality

OR 0.90 (95% CI 0.79-1.02) P=0.10

Stroke

0.9% thrombectomy vs. 0.6% PCI alone, OR 1.43 (95% CI 1.03-1.99) P=0.03

ConclusionsRoutine 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

Available Online at the Lancet

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. YusufThank you for Grant Support from and

TOTAL 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

0.5

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