Non-vitamin K antagonist Oral anticoagulants in patients with Atrial High rate episodes (NOAH)
Atrial fibrillation (AF) is a common cause of stroke. Patients suffering from AF, if documented by an ECG, receive an antithrombotic therapy for stroke prevention consisting of oral anticoagulation treatment with vitamin K antagonists (VKAs) or non-vitamin K antagonist oral anticoagulants (NOACs). However, a large proportion of AF episodes remain undiagnosed (“silent AF”), and many of these patients present with a stroke as the first clinical sign of AF. Earlier initiation of anticoagulation could prevent such events.
Continuous monitoring of atrial rhythm by implanted devices could close this diagnostic gap. Modern pacemakers and defibrillators provide automated algorithms alerting to the occurrence of atrial high rate episodes (AHRE). There is evidence that stroke rate is increased in patients with AHRE. A sizeable portion of these patients develops AF over time. In these patients, AHRE can be considered as an early manifestation of AF. There is uncertainty about the optimal antithrombotic therapy in patients with AHRE.
NOAH – AFNET 6 is a prospective, parallel-group, randomized, open, double-blind, multi-center trial to evaluate the potential benefit of oral anticoagulation therapy in patients with AHRE, but without overt AF. The trial is to test whether treatment with the newly introduced NOAC edoxaban is superior to current therapy to prevent stroke, systemic embolism, or cardiovascular death in this patient group.
The investigator initiated trial will enroll 2.686 patients with AHRE and at least two stroke risk factors (CHA2DS2VASc Score of 2 or more). Patients are eligible for NOAH, if they have an implanted pace-maker or defibrillator with the feature of detection of AHRE and if their device documented AHRE with an atrial rate of at least 180 bpm and at least 6 min duration. Patients with overt AF are not eligible.
200 to 250 study centres in 15 European countries with adequate experience in the follow-up of implanted pacemakers or defibrillators in clinical routine will enroll the patients. The study participants will be randomized to either receiving edoxaban or receiving the current treatment consisting of antiplatelet therapy or no therapy depending on the cardiovascular risk.
Atrial fibrillation (AF) is a common cause of stroke, especially ischemic stroke. So far, all available data that demonstrate a beneficial effect of oral anti-coagulation for stroke prevention have been collected in populations with AF documented by conventional ECG recordings. It is well established that a large proportion of AF episodes remain undiagnosed (“silent AF”), and many of these patients present with a stroke as the first clinical sign of AF. Earlier initiation of anticoagulation could prevent such events. Continuous monitoring of atrial rhythm by implanted devices could close this diagnostic gap. Pace-makers, defibrillators, and cardiac resynchronisation devices already provide automated algorithms alerting to the occurrence of highly organised atrial tachyarrhythmia episodes, also called “subclinical atrial fibrillation” or, more commonly, “atrial high rate episodes” (AHRE). Data from large prospectively followed patient cohorts demonstrated that stroke rate is increased in patients with AHRE. A sizeable portion of these patients develops clinically detected AF over time. In these patients, AHRE can be considered as an early manifestation of paroxysmal AF. A few AHRE patients do not develop clinically overt AF, and the absolute stroke rates are lower in patients with AHRE when compared to stroke rates in patients with clinically diagnosed AF. In light of the bleeding complications associated with oral anticoagulant therapy, there is thus uncertainty about the optimal antithrombotic therapy in patients with AHREs.
The Non-vitamin K antagonist Oral anticoagulants (NOACs) provide similar or slightly better stroke prevention, and appear slightly safer compared to vitamin K antagonists (VKAs). In addition, no individual therapy adjustment of NOACs has to be performed. Edoxaban, a newly introduced NOAC, at a dose regime of 60 mg once daily (OD) has a favourable profile compared to dose-adjusted VKA therapy: In the ENGAGE-TIMI 48 trial, edoxaban prevented strokes at least as effectively as VKA therapy but caused less major bleeding events than VKA therapy.
Investigator-initiated, prospective, parallel-group, randomised, double-blind, multi-centre trial. Although it can be argued that the intervention tested is within the registered label of edoxaban, NOAH – AFNET 6 will be conducted as a phase III b study.
Participating countries and national coordinators
Belgium: Andrea Sarkozy, MD
Bulgaria: Vasil Velchev, MD
Germany: Christopher Piorkowski, MD
France: Eloi Marijon, MD
Greece: Panos Vardas, MD
UK: Neil Sulke, MD
Italy: Emanuele Bertaglia, MD
The Netherlands: Joris de Groot, MD
Austria: Wolfgang Dichtl, MD
Poland: Andrzej Lubinski, MD
Portugal: Nuno Cabanelas, MD
Romania: G.-Andrei Dan, MD
Sweden: Carina Blomstrom Lundqvist, MD
Spain: Lluis Mont, MD
Czech Republic: Dan Wichterle, MD
Hungary: Belá Merkely, MD
Melanie Calvert | Birmingham, UK
John Camm | London, UK
Gregory Chlouverakis | Rhetymno, Greece
Hans-Christoph Diener | Essen, Germany
Andreas Goette | Paderborn, Germany
Paulus Kirchhof (chair) | Hamburg, Germany
Gregory Lip | Birmingham, UK
Emmanuel Simantirakis | Heraklion, Greece
Panos Vardas | Heraklion, Greece
German Centre for Cardiovascular Research (DZHK)
Daiichi Sankyo Europe
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