Newer, more potent antiplatelet agents in addition to antico- agulant therapy are indicated irrespective of initial treatment strategy. Evidence-based decisions will require compara- tive-effectiveness studies of available and novel agents. The paradox of newer and more potent antithrombotic and anti- coagulant drugs that reduce major adverse cardiac outcomes but increase bleeding risk occurs with greater frequency in patients with AF. Patients with AF who develop NSTE-ACS and receive a coronary stent are the population at risk from triple anticoagulant/antiplatelet therapy. This regimen has been reported to be safely modified by elimination of aspirin, a finding that requires confirmation. Among the most rapidly evolving areas in NSTE-ACS diagnosis is the use of cardiac troponin, the preferred bio- marker of myocardial necrosis. Although a truly high-sensi- tivity cardiac troponin is not available in the United States at the time this CPG was prepared, the sensitivity of contempo- rary assays continues to increase. This change is accompa- nied by higher rates of elevated cardiac troponin unrelated to coronary plaque rupture. The diagnostic quandary posed by these findings necessitates investigation to elucidate the opti- mal utility of this advanced biomarker. A promising approach to improve the diagnostic accuracy for detecting myocardial necrosis is measurement of absolute cardiac troponin change, which may be more accurate than the traditional analysis of relative alterations. Special populations are addressed in this CPG, the most numerous of which are older persons and women. More than half of the mortality in NSTE-ACS occurs in older patients, and this high-risk cohort will increase as our population ages. An unmet need is to more clearly distinguish which older patients are candidates for an ischemia-guided strategy compared with an early invasive management strategy.An appreciable number of patients with NSTE-ACS have angiographically normal or nonobstructive CAD, a group in which women predominate. 