Non Vitamin K Oral Anticoagulants (Modified From Section 4.2.2.2., New Target-Specific Oral Anticoagulants, in the 2014 AF Guideline) Most NOACs represent an advance in therapeutic safety when compared with warfarin for prevention of throm- boembolism in patients with AF. The NOAC AF trials demonstrated that NOACs are noninferiorS4.2.2.2-1,S4.2.2.2-2 to warfarin in preventing stroke or thromboembolism. NOACs reduce intracra- nial bleeding as compared with warfarin.S4.2.2.2-1 S4.2.2.2-5 Although no direct RCT data are available, limited data comparing individual NOACs to one another are emerging from meta-analyses of the original NOAC clinical trialsS4.2.2.2-6 and registries and patient and more data are expected. Specific NOACs, such as apixaban, may have lower risks of bleeding (including intracranial hemorrhage) and improved efficacy for stroke prevention, whereas the risk of bleeding for rivaroxaban is comparable to that of warfarin. In other studies, uninterrupted dabi- gatran had a more favorable outcome than warfarin in ablation of AF (RE-CIRCUIT Trial [Uninterrupted Dabigatran Etexilate in Comparison to Uninterrupted Warfarin in Pulmonary Vein Ablation]).S4.2.2.2-15 Over time, NOACs (particularly dabigatran and rivaroxaban) may be associated with lower risks of adverse renal outcomes than warfarin in patients with AF.S4.2.2.2-16 Among older adults with AF receiving anticoagula- tion, dabigatran was associated with a lower risk of osteoporotic fracture than warfarin.S4.2.2.2-17 Data on drug interactions with NOACs are emerging.S4.2.2.2-18 Interpretation of these data requires careful consider- ation of trial design, including factors such as absence of control groups, incomplete laboratory and histori- cal data, missing data for some drugs (particularly edoxaban), and varying NOAC drug doses (some ap- proved doses in the United States differ from those in Europe). Head-to-head prospective RCT data for NO- ACs are needed for further evaluation of comparative bleeding risk and effectiveness. 