Several observational studies have demonstrated the safety and feasibility of treating AIS with thrombin inhibitors as either a single or an adjunct therapy to alteplase. The oral direct thrombin inhibitor dabigatran was studied in 53 patients with TIA or minor stroke (NIHSS score 3) with no occurrences of sICH up to 30 days.224 ARTSS (Argatroban With Recombinant Tissue Plasminogen Activator for Acute Stroke)-1 was an open-label, pilot safety study of argatroban infusion plus IV alteplase in 65 patients with complete or partially occlusive thrombus diagnosed by transcranial In the ARTSS-2 phase II study, patients with AIS treated with alteplase (N=90) were randomized to receive placebo or argatroban (100- g/kg bolus), followed by infusion of either 1 (low dose) or 3 (high dose) g/kg per minute for 48 hours. Rates of sICH were similar among the control, low-dose, and high-dose arms: 3 of 29 (10%), 4 of 30 (13%), Further trials are necessary to clarify the safety and efficacy of this intervention. See Tables XLIX and L in online Data Supplement 1. The safety and usefulness of oral factor Xa inhibitors in the treatment of AIS are not well established. IIb C-LD New recommendation. Limited data exist on the use of factor Xa inhibitors (eg, rivaroxaban, apixaban, edoxaban) for treatment of patients with AIS.227 Several prospective observational studies and early-phase trials are ongoing (NCT02279940, NCT02042534, NCT02283294). Further clinical trials are needed. See Table LI in online Data Supplement 1. Urgent anticoagulation, with the goal of preventing early recurrent stroke, halting neurological worsening, or improving outcomes after AIS, is not recommended for treatment of patients with AIS. III: No Benefit A Recommendation and LOE unchanged from 2013 AIS Guidelines. COR amended to conform with ACC/AHA 2015 Recommendation Classification System. 