CREATE

1
TIMACS

Tim
ing of Intervention

in patients with


A
cute
C
oronary
S
yndromes
An International Randomized Trial of Early Versus
Delayed Invasive Strategies in Patients with
Non-ST Segment Elevation Acute Coronary Syndromes
Shamir R. Mehta MD On behalf of the TIMACS
Investigators
2
Design, Eligibility Criteria and Protocol
UA or NSTEMI 2 of 3 Criteria Age gt 60, ischemic
EKG ? or ? biomarker AND suitable for
revascularization
Excluded Contraindication for LMWH or high risk
of bleeding or not a suitable candidate for
revascularization
ASA, clopidogrel, GP IIb/IIIa antagonist as per
routine practice
RANDOMIZE
Early Invasive Coronary angiography as soon as
possible followed by PCI or CABG (no later than
24 hours)
Delayed Invasive Coronary angiography any time
gt36 hrs followed by PCI or CABG
Center chose randomization ratio 11, 12 or 21
Early Delayed
3
Outcomes

• Primary
• Composite of Death, new MI or Stroke at 6 mo.
• Secondary
• Composite of
• Death, new MI or refractory ischemia
• Death, new MI, stroke, refractory ischemia or
  repeat revascularization
• Stroke

4
Primary and Secondary Outcomes
Early N1,593 Delayed N1,438 HR 95 CI P
Death, MI, Stroke 9.7 11.4 0.85 0.68-1.06 0.15
Death, MI, refractory ischemia 9.6 13.1 0.72 0.58-0.89 0.002
Death, MI, Stroke, refractory ischemia repeat intervention 16.7 19.7 0.84 0.71-0.99 0.039
Death 4.9 6.0 0.81 0.60-1.11 0.19
MI 4.8 5.8 0.83 0.61-1.14 0.25
Stroke 1.3 1.4 0.90 0.48-1.68 0.74
Ref. Ischemia 1.0 3.3 0.30 0.17-0.53 lt0.00001
Rep. Intervention 8.8 8.6 1.04 0.82-1.34 0.73
5
Primary OutcomeDeath, MI, or Stroke
Death/MI/Stroke at 180 days
Delayed
Early
0.10
Cumulative Hazard
0.06
HR 0.85 95 CI 0.68-1.06 P 0.15
0.02
0.0
0
30
60
90
120
150
180
Days
No. at Risk
Delayed
1438
1328
1269
1254
1234
1229
1211
Early
1593
1484
1413
1398
1391
1382
1363
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Secondary OutcomeDeath, MI, or refractory
ischemia
HR 0.72 95 CI 0.58-0.79 P0.002
7
Secondary OutcomeDeath, MI, stroke, RFI or Rep
Intervention
Death/MI/RI/Stroke/Rep Int at 180 days
HR 0.84 95 CI 0.71-0.99 P0.039
8
GRACE Risk Score Primary Outcome
HR 0.65 95 CI 0.48-0.88 P0.005
Death, MI or Stroke at 6 mo.
Interaction P0.0097
HR 1.14 95 CI 0.82-1.58 P0.43
Low/Int Risk GRACE Score lt 140 N2070
High Risk GRACE Score gt 140 N961
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Conclusions

1. Overall, we found no significant difference
   between an early and a delayed invasive strategy
   for prevention of death, MI or stroke (primary
   outcome).
2. However, in the subgroup at highest risk (GRACE
   score gt 140), an early invasive strategy was
   superior to a delayed invasive strategy for
   prevention of death, MI or stroke
3. Early invasive strategy also had a large impact
   on reducing the rate of refractory ischemia by
   70.
4. There were no significant differences in major
   bleeding or other safety concerns between the two
   strategies

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Implications

1. Most patients with ACS can be managed safely with
   either an early or a delayed invasive strategy
2. In a subset of patients at highest risk (GRACE
   scoregt140), early intervention is superior and
   these patients should be taken to the cath lab
   early
3. In all other patients, the decision regarding
   timing of intervention can depend on other
   factors, such as cath lab availability and
   economic considerations.