Three trials have compared different strategies of early versus delayed intervention in patients with UA/NSTEMI and form the basis of the updated recommendations in this guideline. The ISAR-COOL (Intracoronary Stenting with Antithrom- botic Regimen Cooling-Off) trial122 carried out at 2 hospitals between 2000 and 2002 randomized 410 patients with unstable chest pain and either electrocardiographic ST-segment depres- sion or elevated troponin levels to undergo coronary angiogra- phy within 6 hours of presentation (median 2.4 hours) or after 3 to 5 days (median 86 hours) of antithrombotic pretreatment.122 Patients with large MI, defined by ST-segment elevation or creatine kinase myocardial band isoenzyme activity 3 times normal, were excluded. Underlying medical therapy in both treatment arms included aspirin, clopidogrel, UFH, and tiro- fiban. By 30 days follow-up, the primary endpoint of death or large MI (defined by new electrocardiographic Q waves, left bundle-branch block, or creatine kinase myocardial band eleva- tion 5 times normal) occurred in 11.6% of patients randomized to delayed catheterization versus 5.9% of those in the early angiography group (P 0.04). Differences between treatment groups were observed exclusively in the period before catheter- ization, with identical event rates in the 2 arms after angiogra- phy. Although providing evidence that a strategy of cooling- off for 3 to 5 days before angiography does not improve outcome in this setting, the findings of this trial were limited because of the small sample size and the prolonged delay before angiography in the medical pretreatment arm. Information more relevant to contemporary practice pat- terns was provided in the 2009 publication of the large-scale multicenter TIMACS (Timing of Intervention in Acute Cor- onary Syndromes) trial,107 which compared early versus delayed angiography and intervention in patients with non Jneid et al 2012 UA/NSTEMI Focused Update 885 Table 2. 