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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. Primary and secondary outcomes in TIMACS hazard ratio (95% CI), early vs delayed strategies End point HR (95% CI) 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 *Primary end point Mehta SR et al. American Heart Association 2008 Scientific Sessions; November 10, 2008; New Orleans, LA. p Rates of death, MI, or stroke within six months according to GRACE risk level and HR (95% CI), early vs delayed Risk level by Early Delayed HR (95% CI) GRACE score* (%) (%) Low/ intermediate (n=2070) 7.7 6.7 High (n=961) 14.1 21.6 p 1.14 (0.82–1.58) 0.43 0.65 (0.48–0.88) 0.005 *Low/intermediate risk=GRACE score <140 High risk=GRACE score >140 Mehta SR et al. American Heart Association 2008 Scientific Sessions; November 10, 2008; New Orleans, LA. GRACE score – predicts the risk of in-hospital mortality Arch Intern Med 2003;163:2345-2353 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”.