AB London 27/1/2005 Andreas Baumbach Bristol Heart Institute Bristol Royal Infirmary.

ABLondon 27/1/2005

Andreas BaumbachBristol Heart Institute

Bristol Royal Infirmary

AB

Revascularisation in ACS

ICTUS

MERLIN

REACT

4mins

4mins

4mins

Tony’s Comments15mins

AB

ICTUS

Comparison of an early invasive with a selective invasive strategy

in pts presenting with Trop positive ACS

ESC München 2004

ESC Hotline-II

Robbert J de Winter MD PhD FESC

Academic Medical CenterDepartment of Cardiology

University of Amsterdam

No financial interests to disclose

ESC München 2004

Design

Inclusion criteria

• Anginal symptoms at rest < 24 hours

• Troponin T concentration 0.03 ng/L

• And one of the following:

Documented history of coronary artery disease

Ischemic changes on the ECG

ST-segment depression 0.05 mV

Transient ST‑segment elevation

T-wave changes 0.2 mV in two contiguous leads

ESC München 2004

NSTE-ACSTrop T pos Death, MI, or ACS

Abciximab during all PCI procedures

Selective invasive

Early invasive

AspirinEnoxaparinClopidogrel

Statins

CAG Medical Rx

PCI / CABG

Medical Rx

CAG / PCI / CABG

ETT

Chest pain

- 24 hrs

Random.

0 hrs

Refractory angina

-

+

24-48 hrs

1 year

Design

Study design

ESC München 2004

1o endpoint: Death, MI*, Rehospitalization for ACS

Power: Early invasive strategy superior

Endpoint reduction from 28% to 21%

80% power

Sample size: 2 x 600 patients

Design

Statistics

*Peak CK-MB > 1 x ULN; serial sampling every 6 hrs In patients with elevated CK-MB at randomization,

at least 50% decrease with subsequent rise > 1 x ULN

ESC München 2004

Results

Results

• 42 participating Dutch centers, 12 intervention centers

• 1201 patients randomized between July 2001- August 2003

Early invasive: 604 patients

Selective invasive: 597 patients

• One year follow-up (August 20th 2004), 98% complete

ESC München 2004

100 200 300

20%

40%

60%

80%

100%

73%

47%

Early invasive

Selective invasive

Time (days)

Results

Revascularization over time

Early invasive: 97% CAGSelective invasive: 67% CAG

Highest Angio/Revascularisation Rate

ESC München 2004

10%

20%

30%

100 200 300

Early invasive

Selective invasive

Death, MI, Rehospitalization for ACS

21.7%

20.4%

Results

Relative Risk: 1.0695% CI: 0.85 – 1.32

P = 0.59

Time (days)

ESC München 2004

Events at one year

Death

New or recurrent MI

Rehosp. for ACS

Primary endpoint

P-value

0.86

0.006

0.017

0.59

2.2

14.6

7.0

21.7

Earlyinvasive

(%)

2.0

9.4

10.9

20.4

Selectiveinvasive

(%)

Results

1.07

1.55

0.63

1.06

RelativeRisk

No difference in Angina

AB

Conclusion1. An early invasive strategy was not

superior to a selective invasive strategy for NSTE-ACS

2. Use of active risk stratification, and liberal use of coronary angiography is a good treatment option

3. The treadmill is back !

AB

MERLIN

Comparison of Rescue angioplasty for failed thrombolysis with a

conservative strategy

MERLIN

Mark de Belder

The James Cook University Hospital

Middlesbrough

Is rescue angioplasty worth it?

MERLINMETHODS

Inclusion Criteria

• STEMI and evidence of “failure to reperfuse” • Presentation to hospital within 10 hours of

symptoms • “Failure to reperfuse” at 60 min ECG:

Failure of the ST segment elevation in the worst lead to have resolved by 50%

Endpoints• Primary end point:

30 day all cause mortality

• Secondary endpoints: i) 30 day composite of death, reinfarction, stroke, heart failure, unplanned revascularisation ii) Left ventricular function at 30 days assessed by the RWMI.iii) Further analysis at 6, 12, 24, 36 months

MERLIN Results: 30 days

0

10

20

30

40

50%

Primary endpoint Composite secondary endpoint

Rescue N:154 Conservative N:153

p=0.7

p=0.02

0

5

10

15

20

25

30%

Dea

th

ReM

I

Str

oke

Unp

lann

ed

reva

sc CCF

P=0.7

P=0.3

P=0.03

P=0.0004

P=0.3

11.1

1.3

0

2

4

6

8

10

12

%

Rescue Conservative

Transfusions

Sutton AGC, Campbell PG, Graham R et al. JACC 2004;44:287-96

9.8 11

MERLINResults in the elderly

0

5

10

15

20

25

%

<56 56-65 66-75 >75

MERLIN: 30 day deaths

ConsRescue

30 day Kaplan-Meier survival curve

0 10 20 300

25

50

75

100

%

Days

Conservative

Rescue

p=0.7

30 day Kaplan-Meier event free survival curve

0 10 20 300

25

50

75

100

Days

%

p=0.02Conservative

Rescue

MERLIN – 1yr event free survival

p=0.005

0 100 200 300 400 0

25

50

75

100

Days

Conservative Rescue

0 100 200 300 400 0

25

50

75

100

Days

Conservative Rescue

MERLIN – 1yr survival

AB

Conclusion1. No early mortality benefit

2. Less urgent revascularisations

3. At 1 yr there is no mortality benefit for a strategy of rescue angioplasty

based on the 60 mins ECG

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REACT

Comparison of Rescue angioplasty, repeat thrombolysis and

conservative treatment for failed thrombolysis

Steering CommitteeSteering CommitteeSteering CommitteeSteering Committee

A.H.Gershlick (PI) A.H.Gershlick (PI) M de Belder M de Belder H H Swanton Swanton

R.Wilcox R.Wilcox K Abrams K Abrams

David de BonoDavid de Bono

A.H.Gershlick (PI) A.H.Gershlick (PI) M de Belder M de Belder H H Swanton Swanton

R.Wilcox R.Wilcox K Abrams K Abrams

David de BonoDavid de Bono

Data & Safety Data & Safety Data & Safety Data & Safety

End Point CommitteeEnd Point CommitteeEnd Point CommitteeEnd Point Committee

Kim FoxKim Fox

J. BirkheadJ. Birkhead

M. Bland M. Bland

Kim FoxKim Fox

J. BirkheadJ. Birkhead

M. Bland M. Bland J.HamptonJ.Hampton

S DaviesS Davies

J.HamptonJ.Hampton

S DaviesS Davies

Trial Co-Ordinators/ MonitorsTrial Co-Ordinators/ Monitors Sarah HughesSarah Hughes

Amanda Stephens-LloydAmanda Stephens-LloydIndependent StatisticianIndependent Statistician

Suzanne Stevens/ Alan Skene Suzanne Stevens/ Alan Skene

Trial Co-Ordinators/ MonitorsTrial Co-Ordinators/ Monitors Sarah HughesSarah Hughes

Amanda Stephens-LloydAmanda Stephens-LloydIndependent StatisticianIndependent Statistician

Suzanne Stevens/ Alan Skene Suzanne Stevens/ Alan Skene

Dr N UrenDr N Uren

Dr A de BelderDr A de Belder

Dr J DavisDr J Davis

Dr M PittDr M Pitt

Dr F AlamgirDr F Alamgir

Dr A BanningDr A Banning

Dr A BaumbachDr A Baumbach

Dr MF ShiuDr MF Shiu

Dr B VallanceDr B Vallance

Dr P SchofieldDr P Schofield

Dr K DawkinsDr K Dawkins

Prof P WeissbergProf P Weissberg

Dr R HendersonDr R Henderson

Dr E LeathamDr E Leatham

Dr M MalekianDr M Malekian

Dr M Millar-CraigDr M Millar-Craig

Dr S RedwoodDr S Redwood

Dr S OdemuyiwaDr S Odemuyiwa

Dr P WalkerDr P Walker

Dr E LeeDr E Lee

Dr K OldroydDr K Oldroyd

Dr D O'NeillDr D O'Neill

Dr N CurzenDr N Curzen

Dr S HoodDr S Hood

Dr D HackettDr D Hackett

Dr C LawsonDr C Lawson

Dr H SwantonDr H Swanton

Dr R FoaleDr R Foale

Dr W PennyDr W Penny

Dr D SmithDr D SmithDr I SquireDr I Squire

Dr I HudsonDr I HudsonDr M.NorellDr M.Norell

All Investigators

REACT (REscue Angioplasty v Conservative treatment or repeat Thrombolysis)

ECGECG 90 min90 min post (any) thrombolyticpost (any) thrombolytic

ST < 50 % resolution (with or without pain) CONSENT & RANDOMISE

(IF PCI possible within 12hrs of CP)

Conservative 2 nd thrombolytic Coronary Angio 24 iv heparin Acelerated tPA or +/- PCI Reteplase

P. End point: 6/12 ~death/re-infarction/CVA / severe HF

REACT (REscue Angioplasty v Conservative treatment or repeat Thrombolysis)

ECGECG 90 min90 min post (any) thrombolyticpost (any) thrombolytic

ST < 50 % resolution (with or without pain) CONSENT & RANDOMISE

(IF PCI possible within 12hrs of CP)

Conservative 2 nd thrombolytic Coronary Angio 24 iv heparin Acelerated tPA or +/- PCI Reteplase

P. End point: 6/12 ~death/re-infarction/CVA / severe HF

n=427

R -LYSIS (n=142)

CONS (n=141)

R-PCI (n=144)

Overall

AgeAge 61.3 (10.3) y 61.0 (10.7) y 61.1 (11.9) y

Anterior infarct 38.0% 46.8% 42.7% 42.5%42.5%

FIRST LYTICFIRST LYTIC

rPA 30.3% 19.9% 29.2% 26.5%

SK 57.7% 62.4% 58.3% 59.5%59.5%TNK 1.4% 3.5% 2.1% 2.3%

tPA 10.6% 14.2% 10.4% 11.7%

Stents 68.5%

GP IIb/IIIa 43.4%

RESULTS RESULTS

Primary composite endpoint:Death and non-fatal re-AMI, CVA , Severe HFPrimary composite endpoint:Death and non-fatal re-AMI, CVA , Severe HF

p= 0.78 p= 0.78

p = 0.0009 p = 0.0009

p = 0.002 p = 0.002

6 Months RESULTS

Gr AN=142

R-LYSIS

Gr AN=142

R-LYSIS

Gr BN=141

Conservative

Gr BN=141

Conservative

Gr CN=144

R-PCI

Gr CN=144

R-PCI

44

(31.0%)44

(31.0%)42

(29.8%)42

(29.8%)22

(15.3%)22

(15.3%)

Rank log p=0.004

R-PCI 84.6% (ci 78.7%-90.5%)

R-Lysis 68.7% (ci 61.1%-76.4%)

Conserv 70.1% (ci 62.5%-77.7%)

RESULTS 6 months RESULTS 6 months

p=0.13

R-PCI 93.8% (ci 89.8%-97.7%)

R-Lysis 87.3% (ci 81.9%-92.8%)

Conserv 87.2% (ci 81.7%-92.7%)

Mortality at 6 months

Hierarchical Analysis at 6 MonthsHierarchical Analysis at 6 Months

Death 12.7 (10.6) 12.8 (9.9) 6.3(5.6)

Re AMI 10.6 8.5 2.1

CVA 0.7 0.7 2.1

Severe HF 7.0 7.8 4.9

Death 12.7 (10.6) 12.8 (9.9) 6.3(5.6)

Re AMI 10.6 8.5 2.1

CVA 0.7 0.7 2.1

Severe HF 7.0 7.8 4.9

Re-Lysis (A) Conservative (B) R-PCI (C) Re-Lysis (A) Conservative (B) R-PCI (C)

B v C p=0.06

B v C p=0.06

A v B v C p=0.007

A v B v C p=0.007

MAJOR MINOR

( > 3g/dl) ( 2g/dl -3 g/dl)

MAJOR MINOR

( > 3g/dl) ( 2g/dl -3 g/dl)

5

15

20

10

OVERT Bld No OVERT Bld OVERT Bld No OVERT Bld OVERT Bld No OVERT Bld OVERT Bld No OVERT Bld

4.9

2.1

18.7

3.5

8.58.4

22/27

(82%) sheath

22/27

(82%) sheath

%%

<0.0003

Bleeding Outcomes Bleeding Outcomes

9/9

(100%) sheath

9/9

(100%) sheath

15.5

6.2

3.53.5

15.6

10.4

ns

Lysis C RPCI Lysis C RPCI Lysis C RPCI Lysis C RPCI

Fatal Bleeding complicationsRescue: 0

Conservative: 3Repeat Thrombolysis: 5

AB

Conclusion

1. REACT shows a clear benefit of rescue angioplasty for failed thrombolysis

2. Comparison with MERLIN will be important

3. Forget Re-thrombolysis !