Atrial Fibrillation COR LOE New, Revised, or Unchanged For most patients with an AIS in the setting of atrial fibrillation, it is reasonable to initiate oral anticoagulation between 4 and 14 days after the onset of neurological symptoms. IIa B-NR Recommendation revised from 2014 Secondary Prevention. A multicenter prospective cohort of 1029 patients with AIS and newly diagnosed atrial fibrillation showed a better composite outcome of stroke, TIA, systemic embolism, sICH, and major extracranial bleeding within 90 days when anticoagulant was initiated 4 to 14 days from stroke onset (HR 0.53 [95% CI, 0.30 0.93] for starting anticoagulation at 4 14 days compared with <4 days); high CHA2 -VASc score, high NIHSS score, large ischemic lesions, and type of anticoagulation were associated with poorer outcomes.378 In a prospective, open-label study of 60 patients with atrial fibrillation and either mild to moderate AIS with NIHSS score <9 (n=49) or TIA (n=11) who were treated with rivaroxaban within14 days of onset, 50 were available for follow-up at 7 days after drug initiation. None developed symptomatic hemorrhagic transformation (HT). Of the 23 with AIS who had HT at baseline, 5 demonstrated asymptomatic radiographic progression, and 18 showed neither clinical nor radiographic progression. Of the remaining 27 who did not have HT at baseline, 3 developed asymptomatic HT.227 See Table LI in online Data Supplement 1. For patients with a history of ischemic stroke, atrial fibrillation, and coronary artery disease, the usefulness of adding antiplatelet therapy to oral anticoagulants is uncertain for purposes of reducing the risk of ischemic cardiovascular and cerebrovascular events. Unstable angina and coronary artery stenting represent special circumstances in which management may warrant dual antiplatelet/oral anticoagulation. IIb C-LD Recommendation reworded for clarity from 2014 Secondary Prevention. COR unchanged. LOE amended to conform with ACC/AHA 2015 Recommendation Classification System. 