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

2. AB Revascularisation in ACS ICTUS MERLIN REACT 4mins Tony’s Comments 15mins

3. AB ICTUS Comparison of an early invasive with a selective invasive strategy in pts presenting with Trop positive ACS

4. ESC München 2004 ESC Hotline-II Robbert J de Winter MD PhD FESC Academic Medical Center Department of Cardiology University of Amsterdam No financial interests to disclose

5. 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

6. ESC München 2004 NSTE-ACS Trop T pos Death, MI, or ACS Abciximab during all PCI procedures Selective invasive Early invasive Aspirin Enoxaparin Clopidogrel 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

7. ESC München 2004 1 o 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

8. ESC München 2004 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 20 th 2004), 98% complete

9. ESC München 2004 100200300 20% 40% 60% 80% 100% 73% 47% Early invasive Selective invasive Time (days) Results Revascularization over time Early invasive: 97% CAG Selective invasive: 67% CAG Highest Angio/Revascularisation Rate

10. ESC München 2004 10% 20% 30% 100200300 Early invasive Selective invasive Death, MI, Rehospitalization for ACS 21.7% 20.4% Results Relative Risk: 1.06 95% CI: 0.85 – 1.32 P = 0.59 Time (days)

11. 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 Early invasive (%) 2.0 9.4 10.9 20.4 Selective invasive (%) Results 1.07 1.55 0.63 1.06 Relative Risk No difference in Angina

12. AB Conclusion 1.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 !

13. AB MERLIN Comparison of Rescue angioplasty for failed thrombolysis with a conservative strategy

14. MERLIN Mark de Belder The James Cook University Hospital Middlesbrough Is rescue angioplasty worth it?

15. MERLIN METHODS 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%

16. 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

17. MERLIN Results: 30 days p=0.7 p=0.02 P=0.7P=0.3P=0.03 P=0.0004 P=0.3 Sutton AGC, Campbell PG, Graham R et al. JACC 2004;44:287-96 9.8 11

18. MERLIN Results in the elderly

19. 30 day Kaplan-Meier survival curve 0102030 0 25 50 75 100 % Days Conservative Rescue p=0.7

20. 30 day Kaplan-Meier event free survival curve 0102030 0 25 50 75 100 Days % p=0.02 Conservative Rescue

21. MERLIN – 1yr event free survival p=0.005

22. MERLIN – 1yr survival

23. AB Conclusion 1.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

24. AB REACT Comparison of Rescue angioplasty, repeat thrombolysis and conservative treatment for failed thrombolysis

25. Steering Committee A.H.Gershlick (PI) M de Belder H Swanton R.Wilcox K Abrams David de Bono A.H.Gershlick (PI) M de Belder H Swanton R.Wilcox K Abrams David de Bono Data & Safety End Point Committee Kim Fox J. Birkhead J. Birkhead M. Bland Kim Fox J. Birkhead J. Birkhead M. Bland J.Hampton J.Hampton S Davies J.Hampton J.Hampton S Davies Trial Co-Ordinators/ Monitors Sarah Hughes Amanda Stephens-Lloyd Amanda Stephens-Lloyd Independent Statistician Suzanne Stevens/ Alan Skene Trial Co-Ordinators/ Monitors Sarah Hughes Amanda Stephens-Lloyd Amanda Stephens-Lloyd Independent Statistician Suzanne Stevens/ Alan Skene Dr N Uren Dr A de Belder Dr J Davis Dr M Pitt Dr F Alamgir Dr A Banning Dr A Baumbach Dr MF Shiu Dr B Vallance Dr P Schofield Dr K Dawkins Prof P Weissberg Dr R Henderson Dr E Leatham Dr M Malekian Dr M Millar-Craig Dr S Redwood Dr S Odemuyiwa Dr P Walker Dr E Lee Dr K Oldroyd Dr D O'Neill Dr N Curzen Dr S Hood Dr D Hackett Dr C Lawson Dr H Swanton Dr R Foale Dr W Penny Dr D Smith Dr I Squire Dr I Hudson Dr M.Norell All Investigators

26. REACT ( RE scue A ngioplasty v C onservative treatment or repeat T hrombolysis) ECG 90 min post (any) thrombolytic ST < 50 % resolution (with or without pain) CONSENT & RANDOMISE (IF PCI possible within 12hrs of CP) Conservative 2 nd thrombolytic Coronary Angio 2 4 iv heparin A celerated tPA or +/- PCI R eteplase P. End point: 6/12 ~death/re-infarction/CVA / severe HF REACT ( RE scue A ngioplasty v C onservative treatment or repeat T hrombolysis) ECG 90 min post (any) thrombolytic ST < 50 % resolution (with or without pain) CONSENT & RANDOMISE (IF PCI possible within 12hrs of CP) Conservative 2 nd thrombolytic Coronary Angio 2 4 iv heparin A celerated tPA or +/- PCI R eteplase P. End point: 6/12 ~death/re-infarction/CVA / severe HF

27. n=427 R -LYSIS (n=142) CONS (n=141) R-PCI (n=144) OverallAge61.3 (10.3) y61.0 (10.7) y61.1 (11.9) y Anterior infarct38.0%46.8%42.7%42.5% FIRST LYTIC rPA30.3%19.9%29.2%26.5% SK 57.7%62.4%58.3%59.5% TNK 1.4%3.5%2.1%2.3% tPA10.6%14.2%10.4%11.7% Stents 68.5% GP IIb/IIIa 43.4% RESULTS

28. Primary composite endpoint: Death and non-fatal re-AMI, CVA, Severe HF Primary composite endpoint: Death and non-fatal re-AMI, CVA, Severe HF p= 0.78 p = 0.0009 p = 0.002 6 Months RESULTS Gr A N=142 R-LYSIS Gr A N=142 R-LYSIS Gr B N=141 Conservative Gr B N=141 Conservative Gr C N=144 R-PCI Gr C N=144 R-PCI 44 ( 31.0%) 44 ( 31.0%) 42 (29.8%) 42 (29.8%) 22 (15.3%) 22 (15.3%)

29. 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

30. 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

31. Hierarchical Analysis at 6 Months Death12.7 (10.6) 12.8 (9.9) 6.3(5.6) Re AMI 10.6 8.5 2.1 CVA0.7 0.7 2.1 Severe HF7.07.8 4.9 Death12.7 (10.6) 12.8 (9.9) 6.3(5.6) Re AMI 10.6 8.5 2.1 CVA0.7 0.7 2.1 Severe HF7.07.8 4.9 Re-Lysis (A) Conservative (B) R-PCI (C) B v C p=0.06 A v B v C p=0.007

32. 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 4.9 2.1 18.7 3.5 8.58.4 22/27 (82%) sheath 22/27 (82%) sheath % % <0.0003 Bleeding Outcomes 9/9 (100%) sheath 9/9 (100%) sheath 15.5 6.2 3.5 15.6 10.4 ns Lysis C RPCI Lysis C RPCI Lysis C RPCI Lysis C RPCI Fatal Bleeding complications Rescue: 0 Conservative: 3 Repeat Thrombolysis: 5

33. 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 !