The current manuscript is the second update of the original Practical Guide, published in 2013 [Heidbuchel et al. European Heart Rhythm Association Practical Guide on the use of new oral anticoagulants in patients with non-valvular atrial fibrillation. Europace 2013;15:625-651; Heidbuchel et al. Updated European Heart Rhythm Association Practical Guide on the use of non-vitamin K antagonist anticoagulants in patients with non-valvular atrial fibrillation. Europace 2015;17:1467-1507]. Non-vitamin K antagonist oral anticoagulants (NOACs) are an alternative for vitamin K antagonists (VKAs) to prevent stroke in patients with atrial fibrillation (AF) and have emerged as the preferred choice, particularly in patients newly started on anticoagulation. Both physicians and patients are becoming more accustomed to the use of these drugs in clinical practice. However, many unresolved questions on how to optimally use these agents in specific clinical situations remain. The European Heart Rhythm Association (EHRA) set out to coordinate a unified way of informing physicians on the use of the different NOACs. A writing group identified 20 topics of concrete clinical scenarios for which practical answers were formulated, based on available evidence. The 20 topics are as follows i.e., (1) Eligibility for NOACs; (2) Practical start-up and follow-up scheme for patients on NOACs; (3) Ensuring adherence to prescribed oral anticoagulant intake; (4) Switching between anticoagulant regimens; (5) Pharmacokinetics and drug-drug interactions of NOACs; (6) NOACs in patients with chronic kidney or advanced liver disease; (7) How to measure the anticoagulant effect of NOACs; (8) NOAC plasma level measurement: rare indications, precautions, and potential pitfalls; (9) How to deal with dosing errors; (10) What to do if there is a (suspected) overdose without bleeding, or a clotting test is indicating a potential risk of bleeding; (11) Management of bleeding under NOAC therapy; (12) Patients undergoing a planned invasive procedure, surgery or ablation; (13) Patients requiring an urgent surgical intervention; (14) Patients with AF and coronary artery disease; (15) Avoiding confusion with NOAC dosing across indications; (16) Cardioversion in a NOAC-treated patient; (17) AF patients presenting with acute stroke while on NOACs; (18) NOACs in special situations; (19) Anticoagulation in AF patients with a malignancy; and (20) Optimizing dose adjustments of VKA. Additional information and downloads of the text and anticoagulation cards in different languages can be found on an EHRA website (www.NOACforAF.eu).

Among patients with stable atherosclerotic vascular disease, those assigned to rivaroxaban (2.5 mg twice daily) plus aspirin had better cardiovascular outcomes and more major bleeding events than those assigned to aspirin alone. Rivaroxaban (5 mg twice daily) alone did not result in better cardiovascular outcomes than aspirin alone and resulted in more major bleeding events. (Funded by Bayer; COMPASS ClinicalTrials.gov number, NCT01776424 .).

The current manuscript is an update of the original Practical Guide, published in June 2013[Heidbuchel H, Verhamme P, Alings M, Antz M, Hacke W, Oldgren J, et al. European Heart Rhythm Association Practical Guide on the use of new oral anticoagulants in patients with non-valvular atrial fibrillation. Europace 2013;15:625-51; Heidbuchel H, Verhamme P, Alings M, Antz M, Hacke W, Oldgren J, et al. EHRA practical guide on the use of new oral anticoagulants in patients with non-valvular atrial fibrillation: executive summary. Eur Heart J 2013;34:2094-106]. Non-vitamin K antagonist oral anticoagulants (NOACs) are an alternative for vitamin K antagonists (VKAs) to prevent stroke in patients with non-valvular atrial fibrillation (AF). Both physicians and patients have to learn how to use these drugs effectively and safely in clinical practice. Many unresolved questions on how to optimally use these drugs in specific clinical situations remain. The European Heart Rhythm Association set out to coordinate a unified way of informing physicians on the use of the different NOACs. A writing group defined what needs to be considered as 'non-valvular AF' and listed 15 topics of concrete clinical scenarios for which practical answers were formulated, based on available evidence. The 15 topics are (i) practical start-up and follow-up scheme for patients on NOACs; (ii) how to measure the anticoagulant effect of NOACs; (iii) drug-drug interactions and pharmacokinetics of NOACs; (iv) switching between anticoagulant regimens; (v) ensuring adherence of NOAC intake; (vi) how to deal with dosing errors; (vii) patients with chronic kidney disease; (viii) what to do if there is a (suspected) overdose without bleeding, or a clotting test is indicating a risk of bleeding?; (xi) management of bleeding complications; (x) patients undergoing a planned surgical intervention or ablation; (xi) patients undergoing an urgent surgical intervention; (xii) patients with AF and coronary artery disease; (xiii) cardioversion in a NOAC-treated patient; (xiv) patients presenting with acute stroke while on NOACs; and (xv) NOACs vs. VKAs in AF patients with a malignancy. Additional information and downloads of the text and anticoagulation cards in >16 languages can be found on an European Heart Rhythm Association web site (www.NOACforAF.eu).

Oral edoxaban was noninferior to subcutaneous dalteparin with respect to the composite outcome of recurrent venous thromboembolism or major bleeding. The rate of recurrent venous thromboembolism was lower but the rate of major bleeding was higher with edoxaban than with dalteparin. (Funded by Daiichi Sankyo; Hokusai VTE Cancer ClinicalTrials.gov number, NCT02073682 .).

Idarucizumab completely reversed the anticoagulant effect of dabigatran within minutes. (Funded by Boehringer Ingelheim; RE-VERSE AD ClinicalTrials.gov number, NCT02104947.).

New oral anticoagulants (NOACs) are an alternative for vitamin K antagonists (VKAs) to prevent stroke in patients with non-valvular atrial fibrillation (AF). Both physicians and patients will have to learn how to use these drugs effectively and safely in clinical practice. Many unresolved questions on how to optimally use these drugs in specific clinical situations remain. The European Heart Rhythm Association set out to coordinate a unified way of informing physicians on the use of the different NOACs. A writing group listed 15 topics of concrete clinical scenarios and formulated as practical answers as possible based on available evidence. The 15 topics are: (1) Practical start-up and follow-up scheme for patients on NOACs; (2) How to measure the anticoagulant effect of NOACs; (3) Drug-drug interactions and pharmacokinetics of NOACs; (4) Switching between anticoagulant regimens; (5) Ensuring compliance of NOAC intake; (6) How to deal with dosing errors; (7) Patients with chronic kidney disease; (8) What to do if there is a (suspected) overdose without bleeding, or a clotting test is indicating a risk of bleeding? (9) Management of bleeding complications; (10) Patients undergoing a planned surgical intervention or ablation; (11) Patients undergoing an urgent surgical intervention; (12) Patients with AF and coronary artery disease; (13) Cardioversion in a NOAC-treated patient; (14) Patients presenting with acute stroke while on NOACs; (15) NOACs vs. VKAs in AF patients with a malignancy. Since new information is becoming available at a rapid pace, an EHRA Web site with the latest updated information accompanies this text (www.NOACforAF.eu).

BACKGROUND Andexanet alfa is a modified recombinant inactive form of human factor Xa developed for reversal of factor Xa inhibitors. METHODS We evaluated 352 patients who had acute major bleeding within 18 hours after administration of a factor Xa inhibitor. The patients received a bolus of andexanet, followed by a 2-hour infusion. The coprimary outcomes were the percent change in anti-factor Xa activity after andexanet treatment and the percentage of patients with excellent or good hemostatic efficacy at 12 hours after the end of the infusion, with hemostatic efficacy adjudicated on the basis of prespecified criteria. Efficacy was assessed in the subgroup of patients with confirmed major bleeding and baseline anti-factor Xa activity of at least 75 ng per milliliter (or ≥0.25 IU per milliliter for those receiving enoxaparin). RESULTS Patients had a mean age of 77 years, and most had substantial cardiovascular disease. Bleeding was predominantly intracranial (in 227 patients [64%]) or gastrointestinal (in 90 patients [26%]). In patients who had received apixaban, the median anti-factor Xa activity decreased from 149.7 ng per milliliter at baseline to 11.1 ng per milliliter after the andexanet bolus (92% reduction; 95% confidence interval [CI], 91 to 93); in patients who had received rivaroxaban, the median value decreased from 211.8 ng per milliliter to 14.2 ng per milliliter (92% reduction; 95% CI, 88 to 94). Excellent or good hemostasis occurred in 204 of 249 patients (82%) who could be evaluated. Within 30 days, death occurred in 49 patients (14%) and a thrombotic event in 34 (10%). Reduction in anti-factor Xa activity was not predictive of hemostatic efficacy overall but was modestly predictive in patients with intracranial hemorrhage. CONCLUSIONS In patients with acute major bleeding associated with the use of a factor Xa in-hibitor, treatment with andexanet markedly reduced anti-factor Xa activity, and 82% of patients had excellent or good hemostatic efficacy at 12 hours, as adjudicated according to prespecified criteria. (Funded by Portola Pharmaceuticals; ANNEXA-4 .)

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