Cooling Off?
Early Intervention?
Very Early Intervention?
Steve Holmberg
Sussex Cardiac Centre
NO CONFLICT OF INTEREST
TO DECLARE
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

The Evidence for Intervention
 3 Landmark Trials
FRISC II (2457)
 RITA-3 (1810)
 TACTICS-TIMI 18 (2220)

FRISC II
 Death/MI 6/12
 Revasc
 Endpoint
 Death
 MI
INV
(PCI at 96 hrs)
71%
9.4%
1.9%
7.5%
CON
9%
12.1%
2.9%
9.2%
RITA-3
 Death/MI/Refractory Angina 4/12
 Endpoint
INV
(PCI at 72hrs)
9.6%
CON
14.5%
(Driven by refractory angina)
But:
 Death/MI at 5 years
16.6%
20.0%
TACTICS-TIMI 18
Death/MI/Re-Hospitalisation at 6/12





Endpoint
Death
MI
Rehosp
Revasc
 TIMI Risk
INV
(PCI at 24 hrs)
15.9%
3.3%
4.8%
11.0%
60%
5-7
3-4
0-2
19.5%
16.1%
12.8%
CON
19.4%
3.5%
6.9%
13.7%
36%
30.6%
20.3%
11.8%
TIMI Risk Score
 History




Age
Risk Factors
Known CAD
Aspirin use
65 or older
3 or more
50%+ stenosis
Within 7 days
 Presentation



Recent severe angina within 24hrs
Raised cardiac markers
ST depression 0.5mm or more
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
ISAR-COOL
 Death/MI (CK-MB >5 x ULN) at 30 days (410)
(Clopidogrel 600mg + Heparin + Tirofiban)
 Raised Troponin 67%
 ST Depression 65%
IMMEDIATE
DELAYED
CATH
2.4hr
86hr
ENDPOINT
5.9%
11.6%
ABOARD
 Peak Troponin I (352)
 TIMI RISK > 2
IMMEDIATE
CATH
ENDPOINT
DELAYED
1.2hr
20.5hr
2.0
1.7
(Death/MI/Revasc at 1/12 - No different)
OPTIMA
 Death/MI/Urgent Revasc at 30 days (241)
 Raised Troponin 32%
 ST Depression 37%
CATH
IMMEDIATE
25 mins!
ENDPOINT
60%
DELAYED
25 hrs
39%
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
TIMACS
 3000+
 Troponin Positive
IMMEDIATE
CATH
ENDPOINT 6/12
Death/MI/Stroke
+Ref Isch
DELAYED
14hr
50hr
HR
0.85
0.72
(p=0.15 NS)
(p=0.002)
TIMACS
 Death/MI/Stroke at 6/12 (3000+)
 Troponin Positive
EARLY
CATH
14hr
GRACE Score 140
Low Risk
7.7
High Risk
14.1
DELAYED
50hr
6.7
21.6
(p=0.43 NS)
(p=0.005)
SUMMARY OF KEY TRIALS
2.4
86
410
EARLY SUPERIOR
ABOARD 1.1
20
352
NEGATIVE
OPTIMA
0.5
25
142
LATE SUPERIOR
TIMACS
14
50
3031
NEGATIVE
EARLY SUPERIOR FOR
HIGH RISK GROUP
ISAR
COOL
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
CONCLUSIONS
 Get out of bed rarely (for NSTEMI)
 Next day is probably fine
 The weekend may be too long