nor in 2015. Rotor ablation using contact phase mapping has been questioned, 10 and CAFÉ ablation is not specific enough to be convincing as demonstrated by a large meta-analysis. 11 In contrast, lifestyle modification such as weight loss is remarkably effective in reducing AF burden (10% loss translates into a sixfold AF burden reduction) and in inducing reverse remodelling on left atrial size and left ventricular septal thickness.
12
Stroke preventionDue to the results from large-scale clinical trials, the nonvitamin K antagonist oral anticoagulants (NOACs) are the preferred treatment for stroke prevention in non-valvular AF, as reflected in current ESC guidelines. 13 As the fourth NOAC, edoxaban has been approved in 2015 in many countries including the USA, Switzerland, and Europe based on the results of the ENGAGE AF-TIMI 48 trial.14 During the year 2015, several subgroup analyses of the large NOAC trials have surfaced, including bleeding management and outcome with apixaban, 15 the management of rivaroxaban around catheter ablation for AF (VENTURE-AF), 16 and the outcome of amiodarone co-medication in patients receiving edoxaban, 17 to name just a few. Virtually, all subgroups of the large NOAC trials indicate a consistent benefit and safety of these drugs compared with warfarin, further underlining their overall superiority. This is supported by important realworld data (including those from a prospective registry with rivaroxaban, XANTUS) 18 indicating efficacy and safety, which is in line with that observed in the randomized clinical trials.Arguably, the most exciting novelty in the field of NOACs comes from the development of specific reversal agents ('antidotes'). In a Phase 1 study in healthy men, the monoclonal antibody idarucizumab (specific for dabigatran) was well tolerated with no unexpected or clinically relevant safety concerns, and was associated with immediate, complete, and sustained reversal of dabigatran-induced anticoagulation. 19 Moreover, in a Phase 3 study, idarucizumab was demonstrated to effectively and immediately reverse the anticoagulant effect of dabigatran in patients presenting with serious bleeding or requiring an urgent procedure. 20 As a result, the US Food and Drug Administration has approved the drug in October 2015; the Committee for Medicinal Products for Human Use of the European Medicines Agency has also recently issued a positive opinion, and approval is expected by the end of this year or early 2016. Importantly, idarucizumab is ineffective against Xa-inhibitors; instead, different directly acting antidotes are being developed, including andexanet alfa and PER977. First results are also positive with these agents, and larger-scale clinical trials are anticipated within the year 2016. While these drugs clearly represent an important addition to our portfolio, many aspects in the practical use remain to be determined, including the type of patients and conditions requiring reversal and the time of reinstitution of anticoagulation. These and other issues are elegantly...