timacs

An International Randomized Trial of Early Versus Delayed

Invasive Strategies in Patients with Non-ST Segment Elevation

Acute Coronary Syndromes

TIMACS Timing of Intervention in patients with Acute Coronary Syndromes

Shamir R. Mehta MDShamir R. Mehta MDOn behalf of the TIMACS InvestigatorsOn behalf of the TIMACS Investigators

TIMACSTIMACSTIMACSTIMACS

Preliminary Results as of Nov 7, 2009

Design, Eligibility Criteria and Design, Eligibility Criteria and ProtocolProtocol

UA or NSTEMI2 of 3 Criteria: Age > 60, ischemic EKG Δ or ↑ biomarker

AND suitable for revascularization

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 >36 hrs followed by PCI or CABG

ASA, clopidogrel, GP IIb/IIIa antagonist as per routine practice

*Center chose randomization ratio 1:1, 1:2 or 2:1 Early: Delayed

ExcludedContraindication for LMWH or high risk of bleeding or not a suitable candidate

for revascularization



OutcomesOutcomes

Primary Primary

Composite of Death, new MI or Stroke at 6 mo.Composite of Death, new MI or Stroke at 6 mo.

SecondarySecondary

Composite of: Composite of:

1.1. Death, new MI or refractory ischemiaDeath, new MI or refractory ischemia

2.2. Death, new MI, stroke, refractory ischemia or Death, new MI, stroke, refractory ischemia or repeat revascularizationrepeat revascularization

3.3. StrokeStroke


Preliminary ResultsPreliminary Results

Primary and Secondary Primary and Secondary OutcomesOutcomes

EarlyEarlyN=1,593N=1,593

DelayedDelayedN=1,438N=1,438

HR HR 95% CI95% CI PP

Death, MI, Stroke 9.79.7 11.411.4 0.850.85 0.68-1.060.68-1.06 0.150.15

Death, MI, refractory ischemia

9.69.6 13.113.1 0.720.72 0.58-0.890.58-0.89 0.0020.002

Death, MI, Stroke, refractory ischemia + repeat intervention

16.716.7 19.719.7 0.840.84 0.71-0.990.71-0.99 0.0390.039

Death 4.94.9 6.06.0 0.810.81 0.60-1.110.60-1.11 0.190.19

MI 4.84.8 5.85.8 0.830.83 0.61-1.140.61-1.14 0.250.25

Stroke 1.31.3 1.41.4 0.900.90 0.48-1.680.48-1.68 0.740.74

Ref. Ischemia 1.01.0 3.33.3 0.300.30 0.17-0.530.17-0.53 <0.00001<0.00001

Rep. Intervention 8.88.8 8.68.6 1.041.04 0.82-1.340.82-1.34 0.730.73



Primary OutcomePrimary OutcomeDeath, MI, or StrokeDeath, MI, or Stroke

Days

Cum

ula

tive

Haz

ard

0.0

0.02

0.06

0.10

0 30 60 90 120 150 180

Death/MI/Stroke at 180 days

Early

No. at Risk

Delayed

Early

1438 1328 1269 1254 1234 1229 1211

1593 1484 1413 1398 1391 1382 1363

Delayed

HR 0.8595% CI 0.68-1.06

P= 0.15



Secondary OutcomeSecondary OutcomeDeath, MI, or refractory ischemiaDeath, MI, or refractory ischemia

Days

Cum

ulat

ive

Haz

ard

0.0

0.04

0.08

0.12

0 30 60 90 120 150 180

Death/MI/RI at 180 days

Delayed

Early

No. at Risk

Delayed

Early

1438 1303 1243 1230 1209 1205 1187

1593 1485 1417 1402 1394 1386 1366

HR 0.7295% CI 0.58-0.79

P=0.002



Secondary OutcomeSecondary OutcomeDeath, MI, stroke, RFI or Rep Death, MI, stroke, RFI or Rep InterventionIntervention

Death/MI/RI/Stroke/Rep Int at 180 days

Days

Cu

mu

lativ

e H

aza

rd

0.0

0.05

0.10

0.15

0.20

0 30 60 90 120 150 180

Delayed

Early

No. at RiskDelayed

Early

1438 1250 1166 1150 1128 1118 1097

1593 1400 1321 1304 1287 1276 1256

HR 0.8495% CI 0.71-0.99

P=0.039


Preliminary ResultsPreliminary Results

GRACE Risk Score: Primary GRACE Risk Score: Primary OutcomeOutcome

6.7

21.6

7.7

14.1

0

5

10

15

20

25

Dea

th/M

I/Str

oke

at 6

mo.

(%)

DelayedEarly

HR 1.1495% CI 0.82-1.58

P=0.43

HR 0.6595% CI 0.48-0.88

P=0.005

Interaction P=0.0097

Low/Int RiskGRACE Score < 140

N=2070

High RiskGRACE Score >= 140

N=961

Death, MI or Stroke at 6 mo.



ConclusionsConclusions

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 > 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



ImplicationsImplications

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 score>140), 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.

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