Six RCTs have evaluated mechanical closure of echocardiographically detected PFO to prevent recurrent stroke in patients without obvious cause for their index stroke.311 317 These trials had highly restrictive eligibility criteria that required brain MRI, imaging of the intracranial vasculature, and echocardiography. Meta-analyses of these trials show a significantly reduced risk of recurrent stroke with mechanical closure compared with medical therapy with a number needed to treat of 131.318 320 A network meta-analysis concluded that, in patients <60 years of age, PFO closure probably confers an important reduction in ischemic stroke recurrence compared with antiplatelet therapy alone but may make no difference compared with anticoagulation. PFO closure also incurs a risk of persistent atrial fibrillation and device-related adverse events. Compared with alternatives, anticoagulation probably increases major bleeding.319 Each of these 6 trials had 1 methodological features with a high risk of bias identified, including lack of blinding of participants and personnel, lack of blinding of outcome assessments, incomplete outcome data, and selective See Tables LXXV through LXXVII in online Data Supplement 1. The effectiveness of routine brain MRI to guide treatment selection for prevention of recurrent stroke is uncertain. (See knowledge byte following 6.1, recommendation 1.) IIb B-NR New recommendation. 6.2. Vascular Imaging 6.2. Vascular Imaging COR LOE New, Revised, or Unchanged For patients with nondisabling (mRS score 0 2) AIS in the carotid territory who are candidates for CEA or stenting, noninvasive imaging of the cervical carotid arteries should be performed routinely within 24 hours of admission. I B-NR New recommendation. 