Timing of Intervention in Patients with Acute Coronary

Syndromes (TIMACS)

AHA, 2008

Background

For UA/NSTEMI pts that are treated with an invasive strategy, the timing of catheterization has not been rigorously investigated.

TIMACS: Methods

• Pts with UA/NSTEMI randomized to early invasive strategy (angiography within 24 hrs) or delayed invasive strategy (angiography any time after 36 hrs).

• Primary endpoint: - composite of death, new MI, or CVA at

6 months.• Secondary endpoints:

- death, new MI, or refractory ischemia- death, new MI, CVA, refractory

ischemia, repeat revascularization- CVA

• 3,031 pts enrolled (1,593 pts in early invasive strategy – median time to cath 14 hrs; 1,438 pts in delayed invasive strategy – median time to cath 50 hrs).

• Mean age 65.4 yrs; 35% females.• 77% pts with NSTEMI• 27% pts with DM; 20% pts with h/o MI• ASA (98%), Thienopyridine (87%), BBlockers (86.9%),

Statins (85%), LMWH (64.3%), UFH (24.6%), Fondaparinux (41.5%, part of the pts were enrolled in OASIS), gp2b/3a (23%), bivalirudin (0.5%).

• 25% pts crossed from delayed to early strategy (refractory ischemia, new MI or instability). 12% crossed from early to delayed strategy.

End point HR (95% CI) p

Death, MI, stroke* 0.85 (0.68–1.06) 0.15

Death, MI, refractory ischemia

0.72 (0.58–0.89) 0.002

Death, MI, stroke, refractory ischemia, repeat intervention

0.84 (0.71–0.99) 0.039

Refractory ischemia

0.30 (0.17–0.53)

<0.00001

Mehta SR et al. American Heart Association 2008 Scientific Sessions; November 10, 2008; New Orleans, LA.

Primary and secondary outcomes in TIMACS hazard ratio (95% CI), early vs delayed strategies

*Primary end point

*Low/intermediate risk=GRACE score <140 High risk=GRACE score >140

Rates of death, MI, or stroke within six months according to GRACE risk level and HR (95% CI), early vs delayed

Mehta SR et al. American Heart Association 2008 Scientific Sessions; November 10, 2008; New Orleans, LA.

Risk level by GRACE score*

Early (%)

Delayed (%)

HR (95% CI) p

Low/intermediate (n=2070)

7.7 6.7 1.14 (0.82–1.58) 0.43

High (n=961) 14.1 21.6 0.65 (0.48–0.88) 0.005

Arch Intern Med 2003;163:2345-2353

GRACE score – predicts the risk of in-hospital mortality

TIMACS: Conclusions

• Early invasive strategy in pts with UA/NSTEMI is not superior to delayed invasive strategy with regard to the composite of death, new MI and CVA at 6 months, unless pt is high risk (as assessed by the GRACE risk model).

• Early invasive strategy is superior in reducing the incidence of refractory angina without increasing the risk of bleeding.

• Early invasive strategy can be implemented very early after pt’s admission – no benefit in “cooling pt off”.