The ef cacy and safety of low-dose NOACs (dabigatran 110 mg, rivaroxaban 15 mg, and edoxaban 30 mg), when compared with warfarin, appear similar among Asians and non-Asians. There are several real-world studies from Asia comparing NOACs with warfarin.135,136 Despite low- dose NOACs, such as dabigatran 110 mg or rivaroxaban 15 mg/10 mg, being more commonly used than standard-dose NOACs (dabigatran 150 mg or rivaroxaban 20 mg), the use of NOACs was associated with reduced risk of ischemic stroke or systemic embolization, major bleeding, ICH, and total mortality compared with warfarin. Published data suggest that NOACs are preferentially indicated for stroke prevention in Asians.37 Other Investigational Drugs: Although NOACs are safer than VKAs, serious bleeding still occurs. The potential for bleeding often discourages initiation of anticoagulant therapy in patients deemed to be at high risk of bleeding, and patients who experience a bleed frequently have permanent or prolonged discontinuation of their anticoagulant. Therefore, continued interest remains in developing even safer anticoagulants than thrombin and factor Xa inhibitors. Current investigation has focused on the upstream targets factor XI and factor XII in the contact pathway, as emerging research has elucidated their critical role in thrombosis with minimal or no role in Strategies to target factor XII or factor XI include antisense oligonucleotides that reduce hepatic synthesis of the clotting proteins, monoclonal antibodies that block activation or activity, aptamers, small molecules that block the active site or induce allosteric modulation, and polyanion antagoniststhat attenuate contact activation by nullifying stimulators of the pathway.7 Human data are limited. The factor XI-directed antisense oligonucleotide IONIS-416858 was compared with enoxaparin in 300 patients undergoing elective knee arthroplasty. 