1. Cooling Off? Early Intervention? Very Early Intervention? Steve Holmberg Sussex Cardiac Centre

2. NO CONFLICT OF INTEREST TO DECLARE

3. Invasive Strategy in ACS - is there still a debate?  ICTUS No benefit of invasive strategy out to 5 years Intervention rates high in the ‘conservative’ arm No penalty for early intervention Invasive strategy may facilitate early discharge and obviate readmission

4. The Evidence for Intervention  3 Landmark Trials FRISC II (2457) RITA-3 (1810) TACTICS-TIMI 18 (2220)

5. FRISC II  Death/MI 6/12 INVCON (PCI at 96 hrs)  Revasc71%9%  Endpoint9.4%12.1%  Death1.9%2.9%  MI7.5%9.2%

6. RITA-3  Death/MI/Refractory Angina 4/12 INVCON (PCI at 72hrs)  Endpoint9.6%14.5% (Driven by refractory angina) But:  Death/MI at 5 years16.6%20.0%

7. TACTICS-TIMI 18 Death/MI/Re-Hospitalisation at 6/12 INV CON (PCI at 24 hrs)  Endpoint15.9%19.4%  Death3.3%3.5%  MI4.8%6.9%  Rehosp11.0%13.7%  Revasc60%36%  TIMI Risk 5-7 19.5%30.6% 3-4 16.1%20.3% 0-2 12.8%11.8%

8. TIMI Risk Score  History Age65 or older Risk Factors3 or more Known CAD50%+ stenosis Aspirin useWithin 7 days  Presentation Recent severe angina within 24hrs Raised cardiac markers ST depression 0.5mm or more

9. The Dilemma Delayed Benefit: Plaque passification with medical treatment followed by intervention on more stable plaque Risk: Events that may occur while waiting Early Benefit: Prevention of early events that may have occurred while waiting Rapid diagnosis and early discharge Risk: Potential for early hazard because of intervention on unstable plaque with fresh thrombus

10. ISAR-COOL  Death/MI (CK-MB >5 x ULN) at 30 days (410) (Clopidogrel 600mg + Heparin + Tirofiban)  Raised Troponin 67%  ST Depression 65% IMMEDIATEDELAYED CATH 2.4hr 86hr ENDPOINT 5.9% 11.6%

11. ABOARD  Peak Troponin I (352)  TIMI RISK > 2 IMMEDIATEDELAYED CATH 1.2hr 20.5hr ENDPOINT 2.0 1.7 (Death/MI/Revasc at 1/12 - No different)

12. OPTIMA  Death/MI/Urgent Revasc at 30 days (241)  Raised Troponin 32%  ST Depression 37% IMMEDIATEDELAYED CATH 25 mins! 25 hrs ENDPOINT 60% 39%

13. OPTIMA  End-point driven by ‘small’ MIs CK 1-2 x ULN  Loading with 300mg Clopidogrel  Considering average times to PCI Extravagant conclusion regarding optimal timing of intervention

14. TIMACS  3000+  Troponin Positive IMMEDIATEDELAYED CATH 14hr 50hr ENDPOINT6/12HR Death/MI/Stroke0.85 (p=0.15 NS) +Ref Isch0.72(p=0.002)

15. TIMACS  Death/MI/Stroke at 6/12 (3000+)  Troponin Positive EARLYDELAYED CATH 14hr 50hr GRACE Score 140 Low Risk7.76.7(p=0.43 NS) High Risk14.121.6(p=0.005)

16. SUMMARY OF KEY TRIALS ISAR COOL 2.486410 EARLY SUPERIOR ABOARD1.120352 NEGATIVE OPTIMA0.525142 LATE SUPERIOR TIMACS14503031 NEGATIVE EARLY SUPERIOR FOR HIGH RISK GROUP

17. CONCLUSIONS  Immediate intervention may be beneficial for some Posterior MIs On-going pain Haemodynamic instability  It may be possible to intervene too early Optimal medical therapy is essential Out-of-hours procedures may have inferior outcomes  High risk patients (particularly) should have intervention at the earliest reasonable opportunity

18. CONCLUSIONS  Get out of bed rarely (for NSTEMI)  Next day is probably fine  The weekend may be too long