However, a prospectively defined secondary endpoint of death, MI, or refractory ischemia was significantly reduced by early intervention from 12.9% to 9.5% (HR: 0.72; 95% CI: 0.58 to 0.89; P 0.003), mainly because of a difference in the incidence of refractory ischemia (3.3% versus 1.0% in the delayed versus early intervention arms, respectively; P 0.001). The occurrence of refractory ischemia was asso- ciated with a 4-fold increase in risk of subsequent MI. Moreover, significant heterogeneity was observed in the primary endpoint when stratified according to a prespecified estimation of baseline risk according to the GRACE (Global Registry of Acute Coronary Events) score. Patients in the highest tertile of the GRACE risk score ( 140) experienced a sizeable and significant reduction in the incidence of the primary ische- Table 2. Continued 2012 Focused Update Recommendations 2012 Comments Class IIb 1. For UA/NSTEMI patients in whom an initial conservative (ie, noninvasive) strategy is selected, it may be reasonable to add eptifibatide or tirofiban to anticoagulant and oral antiplatelet therapy.50,51 (Level of Evidence: B) 2007 recommendation remains current. 2. Prasugrel* 60 mg may be considered for administration promptly upon presentation in patients with UA/NSTEMI for whom PCI is planned, before definition of coronary anatomy if both the risk for bleeding is low and the need for CABG is considered unlikely.7,8,78 (Level of Evidence: C) 2011 recommendation remains current. 3. The use of upstream GP IIb/IIIa inhibitors may be considered in high-risk UA/NSTEMI patients already receiving aspirin and a P2Y12 receptor inhibitor (clopidogrel or ticagrelor) who are selected for an invasive strategy, such as those with elevated troponin levels, diabetes, or significant ST-segment depression, and who are not otherwise at high risk for bleeding.50,51,55,56,58 (Level of Evidence: B) modified ( clopidogrel replaced with P2Y12 receptor inhibitor [clopidogrel or ticagrelor]). 4. 