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 pointHR (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 ischemia0.30 (0.17–0.53)< 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) (0.82–1.58)0.43 High (n=961) (0.48–0.88)0.005

Arch Intern Med 2003;163: 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”.