3.0 to 4.0.165-169 A target INR value of 2.0 will result in patients spending a substan- tial proportion of time at subtherapeutic INR levels (ie, ,2.0).170 Given that bleeding risk does not rise substantially until INR levels are .3.0, and particu- larly .4.0, these data from AF populations support an optimal target INR range of 2.0 to 3.0, with a tar- get value of 2.5 to maximize the time spent in the optimal INR range.165-170 5.2 Time in Therapeutic Range For a full discussion of the importance of time in therapeutic range while on adjusted-dose VKA therapy, see Ageno et al171 regarding oral antico- agulation in this guideline. With respect to patients with AF, there are several observational studies indi- cating that increasing time out of range is associated with poorer outcomes (eg, mortality, ischemic stroke, thromboembolism, major bleeding).172-175 6.0 Future Research Approximately one in every three patients with AF also has coronary artery disease.51 However, the opti- mal approach to antithrombotic therapy in these patients is unclear. Research is needed to determine the effect of treatment with oral anticoagulation and aspirin compared with oral anticoagulation alone on patient-important outcomes of vascular death, nonfa- tal stroke, nonfatal MI, nonfatal major extracranial bleeding, and nonfatal systemic embolism. Research is also needed to inform recommendations about dif- ferent antithrombotic therapy regimens for patients with AF undergoing placement of an intracoronary artery stent or who experience an ACS (eg, triple therapy with oral anticoagulation, clopidogrel, and aspirin; dual antiplatelet therapy with clopidogrel and aspirin; or combination oral anticoagulation and aspirin or clopidogrel). 